key: cord-275699-hdmeyomt authors: singh, aminder; sood, neena; narang, vikram; goyal, abhishek title: morphology of covid-19–affected cells in peripheral blood film date: 2020-05-27 journal: bmj case rep doi: 10.1136/bcr-2020-236117 sha: doc_id: 275699 cord_uid: hdmeyomt nan peripheral blood films showing various neutrophils with c-shaped, fetus-like covid nuclei (black arrowheads) with aberrant nuclear projections (blue arrowhead). toxic granulations and vacuolations (yellow arrowhead), ring nuclei (red arrowheads) and elongated nucleoplasm (green arrowheads) are highlighted. giemsa ×200-400. peripheral blood films showing large granular lymphocytes. round to indented nuclei, condensed chromatin, prominent nucleoli in a few, along with abundant pale blue cytoplasm with distinct variably sized azurophilic granules are present (long black arrow). cytoplasmic pod formation (long green arrows) and apoptotic lymphocytes (long red arrow) are highlighted. giemsa ×200-400. peripheral blood films showing activated monocytes with prominent cytoplasmic vacuolisation and a few granules (small red arrow). nuclear blebbing (small green arrow) is also seen. giemsa ×200-400. a 55-year-old previously healthy woman was admitted with fever and cough. chest x-ray and ct showed features of viral pneumonitis. her nasopharyngeal swab was positive for severe acute respiratory distress syndrome coronavirus-2 (sars-cov-2) by reverse transcription (rt)-pcr. her complete blood count (cbc) showed leucocytosis with neutrophilia, relative lymphocytopaenia, and monocytopaenia initially with subsequent improvement in the number of monocytes on the fifth day onwards. we report a detailed analysis of the peripheral blood film (pbf) of a patient with covid-19 during the hospital course which has not been reported hitherto. some peculiar findings were observed in the neutrophils which were never seen in any other infection. neutrophils showed heavily clumped chromatin with toxic granules and cytoplasmic vacuoles. nuclear detachment with elongated nucleoplasm and ring-shaped nuclei were seen with platelet surface attachment. c-shaped, fetus-like nuclei were noted with aberrant nuclear projections, which we named as covid nuclei (figure 1). most of the lymphocytes were seen as large granular lymphocytes (lgl) with round to indented nuclei, condensed chromatin, prominent nucleoli in a few, along with abundant pale blue cytoplasm with distinct variably sized azurophilic granules (figure 2). cytoplasmic pod formation and apoptosis were also observed in a few lymphocytes. these might represent natural killer cells or cytotoxic t lymphocytes. activated monocytes were seen which showed marked anisocytosis with prominent cytoplasmic vacuolisation and few granules. nuclei were large, having fine chromatin with nuclear blebbing in a few. nuclear overlapping by vacuoles was observed in some cells (figure 3). platelets were adequate, with a few giant forms and focal platelet attachment on the surface of images in… learning points ► in peripheral blood film (pbf), neutrophils showed characteristic c-shaped, fetus-like nuclei, elongated nucleoplasm, and ring-shaped nuclei. ► large granular lymphocytes noted, a representation of natural killer cells or cytotoxic t lymphocytes. ► activated monocytes indicated a favourable sign. ► covid-19 viral effects on leucocytes are associated with characteristic changes that can be readily identified on pbf and can be easily and serially monitored, which could help in the diagnosis, prognostication and treatment protocols. copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission. become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com. visit casereports.bmj.com for more articles like this and to become a fellow all forms of leucocytes. her first cbc sample showed normal total leucocyte count (7.4×10 9 /l) with neutrophilia and relative lymphocytopaenia and monocytopaenia. on the fifth day onwards, her cbc started showing monocytosis, which persisted until day 16. relative lymphocytopaenia persisted throughout her stay, along with the presence of lgl on pbf. lgl started appearing on pbf on day 7 onwards. these findings clearly indicated that in covid-19, initial neutrophilia, lymphocytopaenia and monocytopaenia are subsequently accompanied by monocytosis. during the hospital stay, the patient was managed with oral hydroxychloroquine, azithromycin and antipyretics, along with intravenous fluids, bronchodilators and supportive care. the patient was discharged on 8 april 2020 after two negative samples for covid-19. covid-19 is a highly contagious disease caused by sars-cov-2. it originated from the chinese city of wuhan and has reached the pandemic status in just a few months. it has now affected around 300 countries worldwide, causing significant morbidity and mortality. to date more than 254 045 deaths have been reported. 1 there are various challenges to the exact diagnosis of these patients. clinically patients may be asymptomatic carriers. sensitivity and specificity of currently available methods are very variable. 2 we have examined the pbf findings in a patient with covid-19 which can help in the diagnosis and to some extent the prognosis of patients. the inflammatory response and viral effects on leucocytes might be responsible for these changes, which can be readily identified on pbf and can be easily and serially monitored. monocytosis may be associated with favourable outcome, as seen in our patient. 3 understanding of the haematological manifestations of sars-cov-2 is still in the evolving stage. to reach a definite conclusion regarding the specificity and reliability of these viral cytopathic effects in peripheral smear, more patients positive for covid-19 need to be evaluated in larger studies. our goal is to describe the peculiar morphological findings of affected leucocytes, which would help physicians suspect a diagnosis in the absence of a negative rt-pcr or antibody results. if confirmed in larger studies, these morphological features along with blood count would be helpful in the screening, diagnosis and management of these patients at all levels of healthcare. world health organization. novel coronavirus (covid-19) situation diagnostic testing for severe acute respiratory syndrome-related coronavirus-2: a narrative review covid-19 infection induces readily detectable morphological and inflammation-related phenotypic changes in peripheral blood monocytes, the severity of which correlate with patient outcome this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. key: cord-295527-d5laummv authors: el-baba, firas; gabe, danielle; frank, allan title: prolonged rna shedding of the 2019 novel coronavirus in an asymptomatic patient with a vp shunt date: 2020-09-14 journal: bmj case rep doi: 10.1136/bcr-2020-237720 sha: doc_id: 295527 cord_uid: d5laummv a 33-year-old man with paranoid schizophrenia and a ventriculoperitoneal (vp) shunt was sent to our institution from an inpatient psychiatric facility due to concerns for the 2019 novel coronavirus (covid-19). per the facility, the patient had a fever and non-productive cough. on admission, the patient was afebrile and lacked subjective symptoms. a rna reverse transcriptase pcr (rna rt-pcr) test for covid-19 was positive. a chest x-ray contained a small patchy opacity in the right middle lobe and another in the retrocardiac region concerning for pneumonia. inflammatory markers were mildly elevated. he remained covid-19 positive and asymptomatic for 36 days. this case details one asymptomatic carrier’s course with persistently positive covid-19 nasopharyngeal swabs. it demonstrates that a vp shunt could be a possible predisposition for prolonged viral shedding. a 33-year-old man with paranoid schizophrenia and a ventriculoperitoneal (vp) shunt was sent to our institution from an inpatient psychiatric facility due to concerns for the 2019 novel coronavirus . per the facility, the patient had a fever and non-productive cough. on admission, the patient was afebrile and lacked subjective symptoms. a rna reverse transcriptase pcr (rna rt-pcr) test for covid-19 was positive. a chest x-ray contained a small patchy opacity in the right middle lobe and another in the retrocardiac region concerning for pneumonia. inflammatory markers were mildly elevated. he remained covid-19 positive and asymptomatic for 36 days. this case details one asymptomatic carrier's course with persistently positive covid-19 nasopharyngeal swabs. it demonstrates that a vp shunt could be a possible predisposition for prolonged viral shedding. in december 2019, a novel virus, covid-19, was identified in wuhan, china. its origin has since been linked to a large seafood market involved in the illegal selling of live animals. 1 2 the virus has since rapidly spread throughout the world, and was declared a global pandemic by the who on 11 march 2020. 3 as of 21 june 2020 there are 8 708 008 total confirmed cases and 461 715 confirmed deaths globally. 4 however, the actual number of cases is believed to significantly exceed reported cases due to undiagnosed asymptomatic carriers. these asymptomatic carriers as well as pre-symptomatic individuals are essential to the virus' rapid spread with estimated infection rates of 34% and 40% according to the centre of disease control. 5 however, much is still unknown about the intricate interplay between transmission, viral rna shedding patterns, viral loads, infectivity and individual predispositions to prolong viral shedding. a 33-year-old man with paranoid schizophrenia and a ventriculoperitoneal (vp) shunt was sent to our institution from an inpatient psychiatric facility due to concerns for the covid-19. per the facility, the patient had a fever and non-productive cough; however, no records accompanied the patient on arrival to our emergency department. on admission, the patient was afebrile, non-tachycardic, respiratory rate was within normal limits and his oxygen saturation was 100% on room air. the remaining physical examination was unremarkable except for his psychiatric examination, which showed intermittent response to internal stimuli. per hospital policy the following was obtained: nasopharyngeal swab for rna rt-pcr for covid-19, creatine kinase (cpk), c reactive protein (crp), lactate dehydrogenase (ldh), ferritin and a chest radiograph. crp and cpk were mildly elevated at 27.2 mg/l and 286 units/l, respectively. the ldh and ferritin were within normal limits at 221 units/l and 112.5 ng/ml, respectively. the chest radiograph demonstrated a small patchy opacity in the right middle lobe and another in the retrocardiac region concerning for pneumonia (figure 1). the following day, the patient's rna rt-pcr returned positive for covid-19. the patient was court-mandated to live in a long-term inpatient psychiatric facility due to poor insight into his paranoid schizophrenia. consequently, social work was involved in the patient's case. at this point in the covid-19 global crisis, no inpatient psychiatric facility in our system could accommodate a covid-19 positive patient. as a result, the patient remained under the medicine service for a total of 36 days until two consecutive negative nasopharyngeal rna rt-pcr tests were obtained. he was then discharged according to psychiatric recommendations. the patient was admitted under the medicine service to a covid-positive unit requiring both airborne and contact precautions. at the time, there were two major treatment options for covid-19: (1) hydroxychloroquine and (2) high-dose oral corticosteroids. per hospital policy, if an individual had a positive nasopharyngeal swab and a positive chest radiograph, as our patient did, then they qualified for hydroxychloroquine therapy. dosing was 400 mg two times the first day followed by 400 mg daily for 4 days. as he was asymptomatic, he did not qualify for corticosteroid therapy; his oxygen saturation remained at 100% on room air; therefore, no supplemental oxygen was needed during hospitalisation. the remainder of the patient's clinical course was complicated by placement issues with the findings that shed new light on the possible pathogenesis of a disease or an adverse effect community outreach for psychiatric emergencies. once appropriate placement was found, the patient was discharged with follow-up appointments scheduled with his mental health professionals and primary care physician. the novel coronavirus is an enveloped, single-stranded rna virus that belongs to the coronavirus family within the betacoronavirus genus (β-cov). it is the seventh virus of its family that has demonstrated the ability to infect humans. 1-3 6 rapid humanto-human transmission occurs via respiratory droplets such as coughing and sneezing. non-respiratory viral detection in the stool, blood and semen has also been observed, but transmission capability from these sites has not been established. infectivity begins before the onset of symptoms with an estimated mean incubation period of 5 days and basic reproduction number (r 0 ) of 2.5. 5 7 this explains the well-known transmission of presymptomatic and asymptomatic individuals and the exponential spread of infection. the novel virus exhibits marked genetic structural similarity to members within its genus, notably severe acute respiratory syndrome-associated coronavirus (sars-cov). despite variability among amino acid sequencing, the s-protein of the viruses maintain almost identical electrostatic properties allowing covid-19 to use the same ace2 receptor for viral entry as sars-cov. 2 the ace2 receptors are ubiquitous throughout the human body, but are concentrated in the respiratory system, gastrointestinal tract and systemic small vessels. 8 9 these locations correlate with the well-established clinical symptomology of respiratory distress, diarrhoea, vasculitis and anosmia and dysgeusia. ace2 receptors have also been found in the brain. β-covs, including sars-cov, have a well-documented propensity for neuroinvasion; thus, it is reasonable to believe covid-19 shares this tendency. 10 ren et al also showed that the most common coronaviruses may well survive or persist on surfaces in vitro for up to 1 month. 11 these surfaces include plastic, which is the material vp shunts are made out of. therefore, one can postulate that covid-19 may have neuroinvasive potential based on its affinity to the ace2 receptor, and potentially could have prolonged viral survival on the plastic of a vp shunt in vivo. this pathophysiology may explain why our patient with a vp shunt had prolonged viral shedding thus illustrating a vp shunt as a possible predisposition for prolonged viral shedding and a potential viral niche for covid-19. the precise duration and relationships between transmission, viral shedding and infectivity are uncertain. the length of viral shedding is variable and may depend on disease severity. in a retrospective cohort analysis of 191 patients, viral shedding ranged from 8 to 37 days with a median duration of 20 days. 12 another study of 96 patients revealed a median of 21 days in patients with severe disease compared with 14 days in those with mild disease. 13 additional factors associated with extended viral shedding include the male sex, delayed hospital treatment, mechanical ventilation and treatment with glucocorticoids. 14 the longest reported viral shedding is 60 days in a 47-year-old woman including her symptomatic course and ongoing recovery. 15 to our knowledge, our case of viral shedding for 36 days is the longest reported in a relatively young, asymptomatic patient or in a patient with a vp shunt demonstrating a vp shunt as a possible predisposition for prolonged viral shedding and possible asymptomatic infectivity. however, further studies and case reports are needed to draw this conclusion. ► a vp shunt may predispose individuals to prolonged viral shedding of the novel coronavirus. ► further insight into prolonged viral shedding is warranted to know whether this shedding leads to infectivity. ► for persistently positive patients, consider all risk factors for prolonged infectivity. contributors fe-b, dg and af were all involved in this project. all provided substantial contributions to the conception of case report, drafted the original work and revised the copy, all approved the final project and agreed to be accountable for all aspects of the work ensuring that questions related to the accuracy or integrity of any part of the work. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer reviewed. firas el-baba http:// orcid. org/ 0000-0003-1750-0557 figure 1 chest radiograph showing small patchy opacities in the right middle lobe and in the retrocardiac region concerning for pneumonia. the continuing 2019-ncov epidemic threat of novel coronaviruses to global health -the latest 2019 novel coronavirus outbreak in wuhan, china evolution of the novel coronavirus from the ongoing wuhan outbreak and modeling of its spike protein for risk of human transmission a pneumonia outbreak associated with a new coronavirus of probable bat origin world health organization. coronavirus disease (covid-19) situation report-153 coronavirus disease 2019: pandemic planning scenarios a novel coronavirus from patients with pneumonia in china the incubation period of coronavirus disease 2019 (covid-19) from publicly reported confirmed cases: estimation and application tissue distribution of ace2 protein, the functional receptor for sars coronavirus. a first step in understanding sars pathogenesis angiotensin-converting enzyme 2 in the brain: properties and future directions the neuroinvasive potential of sars-cov2 may play a role in the respiratory failure of covid-19 patients stability and infectivity of coronaviruses in inanimate environments clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study viral load dynamics and disease severity in patients infected with sars-cov-2 in zhejiang province, china factors associated with prolonged viral rna shedding in patients with coronavirus disease 2019 (covid-19) persistent viral shedding lasting over 60 days in a mild covid-19 patient with ongoing positive sars-cov-2 key: cord-331517-o5ejfq86 authors: hirayama, takehisa; hongo, yu; kaida, kenichi; kano, osamu title: guillain-barré syndrome after covid-19 in japan date: 2020-10-29 journal: bmj case rep doi: 10.1136/bcr-2020-239218 sha: doc_id: 331517 cord_uid: o5ejfq86 we report the first case of guillain-barré syndrome (gbs) associated with sars-cov-2 infection in japan. a 54-year-old woman developed neurological symptoms after sars-cov-2 infection. we tested for various antiganglioside antibodies, that had not been investigated in previous cases. the patient was diagnosed with gbs based on neurological and electrophysiological findings; no antiganglioside antibodies were detected. in previous reports, most patients with sars-cov-2-infection-related gbs had lower limb predominant symptoms, and antiganglioside antibody tests were negative. our findings support the notion that non-immune abnormalities such as hyperinflammation following cytokine storms and microvascular disorders due to vascular endothelial damage may lead to neurological symptoms in patients with sars-cov-2 infection. our case further highlights the need for careful diagnosis in suspected cases of gbs associated with sars-cov-2 infection. guillain-barré syndrome (gbs) is an acute type of polyradiculoneuropathy, that occurs following immune events such as infection and vaccination. approximately 40%-70% of gbs cases develop following infection, and autoantibodies against glycolipids (mainly ganglioside antibodies) are detected in over 50% of cases. the cause is generally accepted to be an abnormality in the immune process. 1 2 recently, several reports of gbs associated with sars-cov-2 infection have emerged. however, as far as we have investigated, there are still no reports in japan. 3 however, in a review of 37 cases of sars-cov-2-infection-related gbs, less than half of the studies investigated antiganglioside antibodies. 4 furthermore, few reports have provided details related to the antiganglioside antibody investigated, and clear descriptions of the relevant tests are available only for anti-gm1, anti-gq1b and anti-gd1b antibodies. [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] most reported cases (64.8%) of sars-cov-2-infection-associated gbs were of the acute inflammatory demyelinating polyneuropathy type. acute motor and sensory axonal neuropathy and acute motor axonal neuropathy types were observed in 13.5% and 2.7% of cases. 4 in the present report, we discuss a case of axonal-type gbs associated with sars-cov-2 infection, where the patient was tested for various antiganglioside antibodies. furthermore, we review the cases of sars-cov-2-infection-related gbs reported to date, in order to provide insight into the clinical characteristics and pathological mechanisms underlying the disease. our report also highlights the need for clinicians to remain cautious when attempting to diagnose sars-cov-2-infectionrelated gbs, and when using high-dose iv gamma globulin therapy in patients at risk of thrombosis. a 54-year-old woman with a history of asthma was admitted to our hospital in may 2020 with reports of numbness and weakness in her extremities. twenty days prior to the onset of neurological symptoms, she developed cough and fever; oropharyngeal reverse transcriptase pcr test results were positive for sars-cov-2. although she had pneumonia on ct of the chest, oxygen was not needed. therefore, we did not administer additional treatment, and continued budesonide, formoterol fumarate hydrate and montelukast sodium, that were originally being used to treat asthma. in addition, we used betamethasone only for the first 2 days to avoid the risk of exacerbation of asthma. following approximately 2 weeks of treatment, pcr results were negative. however, at that time, she began to experience numbness in the lower extremities, that gradually spread to the upper extremities. within the next week, she began to develop weakness in the extremities. neurological examination revealed no findings suggestive of abnormalities in the central nervous system. tendon reflexes in the upper extremities were normal, although they were absent in the lower extremities. the medical research council scale grade for muscle strength was 4/4 for proximal and 5/5 for distal muscles of the lower extremities, and 4/4 for proximal and 4/4 for distal muscles of the upper extremities; she was able to walk. her modified erasmus gbs outcome score (megos) was 3/9, while her hughes' functional grade was 2. superficial sensation was mildly impaired in the distal extremities, deep sensation was normal and she had no ataxia. blood tests revealed normal blood glucose levels and no findings suggestive of collagen disease, thyroid disease or vitamin abnormalities. cerebrospinal fluid (csf) assessment at admission at approximately 3 weeks after onset revealed normal protein levels and cell counts. all tests for antiganglioside antibodies were negative. the ganglioside antigens used in the elisa were gm1, gm2, gd1a, gd1b, gd3, galnac-gd1a, gt1a, gt1b, gq1b and ga1 (asialo-gm1). ganglioside complexes containing two of the above 10 antigens were also used as described in a previous study. 15 csf was not tested for sars-cov-2 pcr. on admission, the patient's first electrophysiological examination was normal. however, the second examination performed 1 week later revealed decreases in compound muscle action potential (cmap) amplitudes in the case report median, radial and tibial nerves compared with those obtained in the first examination (table 1). since the patient had a history of asthma, we did not perform lumbar mri using a contrast agent. this case fulfilled two of the required features for the diagnosis of gbs based on the criteria described by asbury and cornblath. 16 in addition, several other clinical features strongly supported the diagnosis. she had no systemic symptoms, multiorgan involvement or elevation of serological markers (eg, elevated sedimentation rate or rheumatoid factor) suggestive of vasculitis. furthermore, she had no malignancy or history of exposure to heavy metals and other toxins. although the patient was diagnosed with gbs, she was followed up without iv immunoglobulin therapy due to her megos and functional grade. approximately 2 weeks later, her symptoms had begun to improve, and she was discharged home on day 18; normalisation of the achilles tendon reflex was also observed. an electrophysiological examination performed 1 month later revealed improved cmap amplitude in most nerves. although her weakness had improved, she continued to experience numbness. although the possibility of gbs associated with sars-cov-2 infection remains to be clarified, the number of gbs cases reported between march 2020 and april 2020 is greater than five times that reported in the last 3 years. 17 given that reports have begun to describe gbs and neurological complications following sars-cov-2 infection, the onset of gbs requires special attention. among the 37 patients described by caress et al, 17 were tested for anti-ganglioside antibodies, 15 of whom were negative. in addition, two patients were positive for miller-fisher syndrome, and all were negative for gbs. however, specific description of types of the anti-ganglioside antibodies tested were not provided in many cases. although some reports specifically described the types of antiganglioside antibodies tested, patients appear to have been tested only for anti-gm1, anti-gq1b and anti-gd1b antibodies. 9 10 14 although we tested for various additional antiganglioside antibodies, all tests were negative in the present case as well. gbs was also reported in a case-control study of the 2016 zika virus, where most patients were negative for antiganglioside antibodies, suggesting the existence of unknown antibodies. 18 therefore, it is important to test for as many kinds of antibodies as possible when suspecting gbs associated with sars-cov-2. however, some authors have reported nearly simultaneous development of neurological and respiratory symptoms in patients with covid-19 and gbs. 19 20 thus, the cause of gbs may not be immune related in all cases. previous research has suggested that sars-cov-2 damages the vascular endothelium. 21 therefore, axonopathy may have been caused by a microvascular disorder. in addition, mcgonagle et al proposed that hyperinflammation following macrophage activation syndrome (ie, 'cytokine storm') may be a cause of gbs in patients with sars-cov-2 infection. 22 together, these findings suggest that, if neurological symptoms develop early following the appearance of respiratory symptoms in patients with covid-19, both autoimmune and other factors should be considered in the diagnosis. whittaker et al noted that the gbs associated with sars-cov-2 infection manifests mainly as lower extremity weakness and paraesthesia. 23 similarly, neurological symptoms began in our patient's lower limbs. axonal disorders and lower extremity dominant symptoms may be similar in character to the length-dependent neuropathies observed in patients with microangiopathy. the present case satisfied the essential diagnostic criteria for gbs described by asbury and cornblath, and the patient's clinical course supported the diagnosis of gbs. nonetheless, the csf test yielded atypical findings. in conclusion, our report supports the notion that patients with gbs associated with sars-cov-2 infection tend to test negative for antiganglioside antibodies. in addition to careful diagnosis, further reports are required to elucidate the characteristics and the mechanisms underlying the onset of gbs due to sars-cov-2 infection. contributors th and ok performed and reviewed literature searches, interpreted and drafted the manuscript, and have both agreed to be personally accountable for the accuracy and integrity of the entire work. th performed examination and provided clinical care to the patient. yh and kk analysed the antibody. all authors reviewed and revised the manuscript and approved the final manuscript. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer reviewed. open access this is an open access article distributed in accordance with the creative commons attribution non commercial (cc by-nc 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. see: http:// creativecommons. org/ licenses/ by-nc/ 4. 0/. takehisa hirayama http:// orcid. org/ 0000-0002-3056-3176 patient's perspective i was anxious when covid-19 symptoms improved and neurological symptoms such as numbness and weakness developed. my symptoms gradually progressed and peaked in about 3-4 weeks. my doctor told me that i might have guillain-barré syndrome. i was told about gamma globulin treatment, but i declined that option due to the risk of side effects and the mild nature of my symptoms. after that, the symptoms gradually improved and the weakness disappeared, although the numbness remained. i was satisfied with the treatment protocol. ► patients with guillain-barré syndrome (gbs) associated with sars-cov-2 infection may test negative for many known antiganglioside antibodies. ► careful diagnosis of gbs is required, because peripheral neuropathy in patients infected with sars-cov-2 may have causes other than autoimmune conditions. ► further studies and case reports are required to facilitate discussion of the mechanisms underlying gbs associated with sars-cov-2 infection. the epidemiology of guillain-barré syndrome worldwide. a systematic literature review peripheral neuropathies and anti-glycolipid antibodies guillain-barré syndrome in sars-cov-2 infection: an instant systematic review of the first six months of pandemic covid-19-associated guillain-barré syndrome: the early pandemic experience post sars-cov-2 guillain-barré syndrome guillain-barré syndrome related to sars-cov-2 infection early guillain-barré syndrome in coronavirus disease 2019 (covid-19): a case report from an italian covid-hospital covid-19 may induce guillain-barré syndrome guillain-barré syndrome after sars-cov-2 infection guillain-barré syndrome associated with sars-cov-2 miller-fisher syndrome after sars-cov-2 infection post-infectious guillain-barré syndrome related to sars-cov-2 infection: a case report guillain-barré syndrome associated with leptomeningeal enhancement following sars-cov-2 infection sars-cov-2-associated guillain-barré syndrome with dysautonomia ganglioside complexes as new target antigens in guillain-barré syndrome assessment of current diagnostic criteria for guillain-barré syndrome guillain-barré syndrome in the covid-19 era: just an occasional cluster? guillain-barré syndrome outbreak associated with zika virus infection in french polynesia: a case-control study guillain-barré syndrome related to covid-19 infection guillain-barré syndrome associated with sars-cov-2 infection: causality or coincidence? sars-cov-2 infection leads to neurological dysfunction the role of cytokines including interleukin-6 in covid-19 induced pneumonia and macrophage activation syndromelike disease neurological manifestations of covid-19: a systematic review and current update copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-288608-2y5626qf authors: ramadan, shadi m; kasfiki, eirini v; kelly, ciaran wp; ali, irshad title: an interesting case of small vessel pathology following coronavirus infection date: 2020-09-07 journal: bmj case rep doi: 10.1136/bcr-2020-237407 sha: doc_id: 288608 cord_uid: 2y5626qf vasculitis is a descriptive term for a wide variety of conditions characterised by inflammation of the blood vessels that may occur as a primary process or secondary to an underlying disease. occlusive vasculopathy is a different clinical entity characterised by skin changes and ulceration of the lower extremities because of thrombosis of the small vessels of the dermis and is usually associated with pre-thrombotic conditions. both conditions can be confirmed or excluded by skin biopsy. we report the case of a 63-year-old woman presenting with upper and lower respiratory tract symptoms followed by a vasculitic rash on both legs. the patient underwent extensive radiological and laboratory investigations that were negative apart from positive coronavirus oc43. a biopsy of the skin was performed. considering the clinical presentation and the investigations performed, the diagnosis of small vessel vasculopathy following coronavirus oc43 has been suggested by the authors. vasculitis is a descriptive term for a wide variety of conditions characterised by inflammation of the blood vessels that may occur as a primary process or secondary to an underlying disease. occlusive vasculopathy is a different clinical entity characterised by skin changes and ulceration of the lower extremities because of thrombosis of the small vessels of the dermis and is usually associated with pre-thrombotic conditions. both conditions can be confirmed or excluded by skin biopsy. we report the case of a 63-year-old woman presenting with upper and lower respiratory tract symptoms followed by a vasculitic rash on both legs. the patient underwent extensive radiological and laboratory investigations that were negative apart from positive coronavirus oc43. a biopsy of the skin was performed. considering the clinical presentation and the investigations performed, the diagnosis of small vessel vasculopathy following coronavirus oc43 has been suggested by the authors. numerous microbial agents, including bacteria, viruses, protozoa and fungi, have been described in association with vasculitis. 1 this strong causality is well evidenced with certain types of infection such as hepatitis b virus-related polyarteritis nodosa (pan) and hepatitis c virus-related cryoglobulinaemia, 2 3 while this association between infection and vasculitis is less robust with a wide variety of other infectious pathogens. the work-up for vasculitis is, therefore, extensive and aims to exclude other possible aetiologies of malignancy, autoimmune diseases and other infections. vasculopathy is associated with risk factors predisposing to thrombosis. coronaviridae are reported to be associated with thrombotic events. 4 this is a case that demonstrates potential association of coronavirus oc43 with vascular pathology that the authors believe is post-immune inflammation, but the diagnosis of vasculopathy has been also suggested by experienced clinicians. a 63-year-old woman presented with a 5-day history of coryza, sore throat, dry cough and vomiting. she developed painful leg swelling and a rash 2 days after the emergence of initial symptoms. she denied mouth ulcers, joint pains or eye symptoms. on further systemic enquiry, she described episodes of visual hallucination, which had fully resolved by the time of hospital attendance, and a couple of self-limiting episodes of epistaxis of no haemodynamic significance. she denied haemoptysis and haematuria, and she felt systemically well. she denied any recent drug ingestion apart from her regular medications, which include mirtazapine and quinine sulphate. her medical history was significant for subarachnoid haemorrhage 20 years ago. she stated that she had a similar rash 1 year ago also associated with coryzal symptoms, but in contrast to the current rash, symptoms had resolved spontaneously within 3 days. examination revealed purple discolouration of the toes of both feet with non-blanching purpuric lesions on both legs (figure 1). blisters and haemorrhagic bullae were seen on the medial aspects of both legs and the soles of the feet (figure 2). both feet were tender and warm to the touch with pedal pulses intact bilaterally and no sensory deficit. chest, abdominal, cardiac and neurological examinations were normal. full blood count revealed a mild normocytic, normochromic chronic anaemia (baseline haemoglobin 100×10 9 g/l), normal total and differential white cell counts and low platelets of 68×10 9 /l. a blood film revealed thrombocytopenia, which gradually normalised during the hospital admission. coagulation screen remained normal, including activated partial thromboplastin time (aptt), prothrombin time (pt) and fibrinogen levels. c reactive protein was mildly elevated (27 mg/l). renal and liver function, folate and b 12 levels were all within normal limits. urine dipstick was normal. ct angiography was obtained for whole aorta and bilateral lower limbs, with concurrent ct of the chest, abdomen and pelvis to investigate for arterial thrombus, lymphadenopathy or malignancy. both scans were normal and excluded mechanical causes for this patient's presentation. the patient underwent an extensive vasculitis work-up to further investigate the rash. autoimmune profile (rheumatoid factor, antineutrophil cytoplasmic antibodies, antinuclear antibodies, anti-dsdna, chromatin level, lupus anticoagulant antibody, anticardiolipin antibody, anti-b 2 glycoprotein-1 antibody, anti-ro antibody, anti-la antibody, anti-sm antibody, anti-ribonucleoprotein antibody, anti-jo-1 antibody, ribosomal autoantibody, anticentromere antibody and extractable nuclear antigen scl70 antibody), complement levels, cryoglobulins, cryofibrinogen, bence-jones protein, protein electrophoresis and immunoglobulins were normal (please see although the score according to duke's criteria was 1, infective endocarditis was excluded by normal echocardiography and serial negative blood cultures. a skin punch biopsy was obtained and demonstrated necrosis in the small vessels with inflammatory cells. the differential diagnosis for this case would be between a vasculitic process and a veno-occlusive vasculopathy. the initial clinical presentation was typical of a small vessel vasculitic process, but the skin biopsy was taken after steroid initiation and the results were not diagnostic of small vessel vasculitis. a confirmed preceding coronavirus oc43 infection characterised by coryzal symptoms raised the suspicion of a postviral, anca-negative vasculitis. the normalisation of inflammatory markers and thrombocytopenia without any specific intervention lends support to this hypothesis. extensive negative workup for vasculitis has excluded any other causative pathology. vasculopathy is an important differential diagnosis that is sometimes difficult to distinguish from vasculitis. clinically, the raised palpable purpura was in favour of vasculitis in contrast to the reticular pattern that is usually seen with vasculopathy. 5 histologically, there was no evidence of vessel lumen occlusion to suggest occlusive non-vasculitic vasculopathy. however, in this context, we should acknowledge that differentiation is not always possible because vessel wall infiltration may occur with late occlusive vasculopathy and intravascular thrombosis may complicate vasculitis. 6 treatment while in hospital the patient remained systemically well and afebrile, and the respiratory symptoms and the rash on both ankles resolved quickly, the ischaemic changes on the feet worsened daily despite oral calcium channel blockers, intravenous iloprost therapy and sildenafil. drugs used were oral nifedipine modified release 40 mg two times per day and oral sildenafil 25 mg three times per day. iloprost infusions were abandoned after a 3-day trial due to ineffectiveness. the patient presented with pain and was managed with regular paracetamol, codeine and gabapentin with oral morphine for breakthrough pain. nine days into admission with no clinical improvement, oral steroids were introduced (prednisolone 30 mg once daily). while the vasculitic rash on the ankles responded well, the steroid therapy did not halt disease progression. the process continued to progress, with the distal parts of the feet becoming more dusky and painful. fifteen days into admission, the patient's toes were black and necrotic with no evidence of wet gangrene and were physiologically amputated (figure 3). vasculitis is characterised by inflammation of the blood vessel wall with reactive injury of mural structures, leading to tissue ischaemia and necrosis due to loss of vascular integrity and luminal compromise. vasculitis may occur as a primary process or may be secondary to another underlying aetiology (eg, infection, drugs and malignancy). microbes, including bacteria, viruses, protozoa and fungi, have been incriminated in the pathogenesis of vasculitis. 1 the causal link between hcv and cryoglobulinaemic vasculitis (cv), and hbv and pan and cv are well established. 2 these two entities are included as 'vasculitis associated with probable aetiology' in the 2012 chapel hill consensus conference on the nomenclature of vasculitides. 3 other reported associations between viruses and post-immune vasculitides are less robust and often anecdotal or controversial. the pathogenesis of most vasculitides caused by viruses is incompletely understood and differs depending on the causative organism. both direct endothelial invasion and indirect autoimmune mechanisms have been postulated. 1 coronaviruses (covs) are of the coronaviridae family and are enveloped viruses with a single strand of rna. under electron microscopy, the virions appear as spike-like projections from the virus membrane giving the appearance of a crown. human covs (hcovs) were first described in the 1960s and are now known to comprise a large family of viruses, including 229e, nl63, oc43, hku1, mers-cov, sars-cov-1 7 and sars-cov-2 (covid-19). 8 covs predominantly affect the respiratory tract; however, there is evidence linking them to systemic disease. covid-19 infection has been implicated in the pathogenesis of kawasaki disease. 9 hcov-oc43 and hcov-229e were detected more frequently in brain tissue from multiple sclerosis patients compared with healthy individuals. 10 our patient has been exhaustively investigated for known causes of vasculitis. normal imaging and laboratory investigation has excluded malignancy, and the skin biopsy, although not diagnostic of vasculitis, was taken after steroid initiation and failed to reveal any specific histology, though a vasculitic process could not be excluded. the recent covid-19 pandemic has revealed the particularly vasculopathic activity of some coronaviruses and there is well-documented evidence of covid-19associated vasculitis. 11 12 infection, including with viruses known to have strong association with vasculitis such as hcv, hbv and hiv, has also been investigated. the patient had a similar vasculitic rash 1 year ago, but this had been resolved spontaneously and had never been investigated. therefore, it is difficult to say whether that rash was associated with a similar coronavirus oc43 infection or was related to another pathology. though we do not have diagnostic histology of vasculitis, we believe this to be a case of small vessel vasculitis caused by coronavirus oc43 infection. further research is needed to provide more robust evidence for this potential association. infection-associated vasculitides vasculitis related to viral and other microbial agents 2012 revised international chapel hill consensus conference nomenclature of vasculitides thromboinflammation and the hypercoagulability of covid-19 occlusive nonvasculitic vasculopathy evidence for immunoglobulin-mediated vasculitis caused by monoclonal gammopathy in monoclonal gammopathy of unclear significance prompting oncologic treatment epidemiology, genetic recombination, and pathogenesis of coronaviruses a novel coronavirus from patients with pneumonia in china association between a novel human coronavirus and kawasaki disease neuroinvasion by human respiratory coronaviruses vascular skin symptoms in covid-19: a french observational study complement associated microvascular injury and thrombosis in the pathogenesis of severe covid-19 infection: a report of five cases not detected contributors sr: patient consent, data collection and writing the manuscript. ek: contributed in writing the manuscript. ck: contributed in discussion and reference check. ia: proofread the manuscript.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. ► infection plays an important role as an aetiology or a trigger of certain types of vasculitis and should be included as a part of an extended vasculitis work up. ► despite being predominantly respiratory tract viruses, coronaviruses have been described in association with other systemic diseases. ► this case suggests a potential association between coronavirus oc43 and small vessel pathology.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-281121-pleula62 authors: ameer, nasir; shekhda, kalyan mansukhbhai; cheesman, ann title: guillain-barré syndrome presenting with covid-19 infection date: 2020-09-14 journal: bmj case rep doi: 10.1136/bcr-2020-236978 sha: doc_id: 281121 cord_uid: pleula62 a construction worker in his 30s presented three times in 4 days with progressive upper and then lower limb weakness. on the first two occasions he had no systemic symptoms, but on the third presentation he had fever and cough, starting from day 4 of weakness. examination identified weakness in all four limbs and areflexia, suggesting a peripheral neuromuscular disorder. investigations were consistent with guillain-barré syndrome and additional covid-19 (sars-cov-2) infection. the patient improved after immunoglobulin treatment. at least four cases of guillain-barré syndrome have been reported in the literature with concurrent covid-19 illness in whom respiratory signs appeared a few days after the onset of neurological signs. with the incubation period for covid-19 respiratory symptoms believed to be up to 14 days, it is possible that neurological symptoms could develop before respiratory and other symptoms. during the current pandemic, presence of concurrent covid-19 infection needs to be considered in patients presenting with guillain-barré syndrome. the recent outbreak of covid-19 (sars-cov-2) became an international pandemic in a short space of time. the majority of patients with covid-19 infection demonstrate fever and respiratory illness. here, we report a case of a patient with covid-19 who presented with guillain-barré syndrome. we report the case of a georgian construction worker in his 30s who presented to the emergency department having developed numbness in his hands the day before, and now with hand weakness, making it difficult to squeeze a lemon, followed by subjective leg weakness. on examination, power was medical research council (mrc) grade 4/5 in his dominant left hand and was felt to be normal in both legs with downgoing plantar responses. deep tendon reflexes were not recorded. he was reviewed by the acute medical team and ct head was normal. he was discharged home, to return if needed. he returned the following day, now with pain in his forearms and calves, and increased weakness and numbness in his feet. review by the orthopaedic team found power to be of mrc grade 4/5 in bilateral wrist flexors and normal in his legs, although he had difficulty standing from sitting. deep tendon reflexes were not recorded. cervical and lumbar spine x-rays were normal. urgent mri of the cervical spine could not be performed due to a bullet in his left hand, confirmed on x-ray. he was discharged home with advice to return if required. he came for the third time to the emergency department 2 days later, day 5 of weakness, this time with cough and fever starting on day 4, unable fully to lift his arms and with difficulty standing. he was normally fit and well and was taking no medications. he had no history of recent illness, no spinal pain and no sphincter disturbance. he had experienced regular epistaxis for over 2-3 weeks which had not occurred since childhood. he lived with his partner, was an ex-smoker and had travelled to latvia for christmas 3 months before and to prague 4 weeks before, with a brief change in bowel habit. there had been no insect bites. he had already decided to stop work on the day the weakness started as he was worried there was insufficient social distancing on-site to protect against covid-19. he was worried that the weakness was due to thyroid dysfunction, of which he had a family history. examination identified a temperature of 38.3°c, blood pressure of 174/110 mm hg and heart rate of 101 beats per minute. there was no facial weakness, but there was symmetrical limb weakness, with an mrc grade of 3/5 for shoulder abduction, 4/5 for wrist dorsiflexion, 2/5 for finger extension, 3/5 for hip flexion, 3/5 for ankle dorsiflexion and 4/5 for ankle plantar flexion. he was areflexic with downgoing plantar responses. vibration, joint position sense, temperature and light touch sensation were all intact. forced vital capacity (fvc) was 4.7 l (85% predicted). he was admitted with suspected covid-19 infection and potential guillain-barré syndrome. urea and electrolytes, liver function tests, thyroid function tests and creatine kinase were normal. total white cell count and c-reactive protein were initially normal. there was lymphopaenia of 0.81×10⁹/l (reference range 1.0-4.5×10⁹/l), raised monocyte count of 1.02×10 9 /l (reference range 0.2-0.8×10 9 / l), patchy perihilar airspace shadowing on chest x-ray and covid-19 rna was positive on nasal and throat swab. his 12-lead ecg showed mild first-degree heart block of 220 ms pr interval, while echocardiogram was unremarkable. lumbar puncture yielded cerebrospinal fluid (csf) with white cell count <0.001×10 9 /l (<1/mm 3 ), protein 1.15 g/l (reference range 0.15-0.45 g/l), csf glucose 3.3 mmol/l and plasma glucose 5.3 mmol/l (normal csf glucose approximately two-thirds the plasma glucose). herpes simplex virus types 1 and 2 new disease dna, varicella zoster virus dna, enterovirus rna and covid-19 rna were not detected in csf. serum antiganglioside antibodies, antinuclear antibodies (ana), anti-neutrophil cytoplasmic antibodies (anca), hepatitis b, hepatitis c, hiv, syphilis, cytomegalovirus igm, epstein-barr virus igm, mycoplasma igm tests and lyme disease serology were negative, as were urinary legionella and pneumococcal antigen tests. stool samples were not taken. nerve conduction studies were not performed initially due to coronavirus restrictions, but were performed 4 weeks after the onset of weakness. these showed the following: ► all recorded motor responses were low in amplitude in both the upper and lower limbs, supporting axonal loss, proximal greater than distal. for example, right tibial nerve response amplitude when stimulated at the popliteal fossa was 1.0 mv and at the ankle was 2.1 mv (tibial nerve amplitude normal at ≥4 mv). ► all recorded motor conduction velocities were borderline slow, for example, the conduction velocity of the right tibial nerve segment from popliteal fossa to ankle was 39 m/sec (normal ≥41 m/sec). (normal values given will vary with age, height and temperature.) differential diagnoses included acute pathologies of the nerve roots (radiculopathies), brachial and lumbosacral plexuses, peripheral nerves, neuromuscular junctions and muscle, with conditions including guillain-barré syndrome, plexopathies, vasculitic neuropathy and lyme disease (prevalent in latvia). the sensory symptoms and normal creatine kinase pointed away from a muscle disorder. the history, the symmetry on examination and csf analysis were typical of guillain-barré syndrome or lyme polyradiculoneuritis, with albuminocytological dissociation (high csf protein with normal cells). nerve conduction studies supported a motor process affecting the axons both in the roots and nerves: a motor polyradiculoneuropathy. negative lyme serology gave a diagnosis of acute motor axonal neuropathy subtype of guillain-barré syndrome. intravenous immunoglobulins were given at 0.4 g/kg/day for 5 days. fvc and limb power were closely monitored. subcutaneous low molecular weight heparin was given, particularly important in this patient with an increased risk of thrombosis from both lower motor neurone syndrome and covid-19, which can result in a hypercoagulable state. the patient received daily physiotherapy, focusing both on respiratory and physical function. following immunoglobulin therapy, the patient showed significant improvement, with power in all limb muscle groups in the range mrc grade 4−/5 to 4+/5. he remained areflexic with no sensory nor autonomic disturbance, except for the prolonged pr interval. post-treatment fvc was 4.9 l (89% predicted). the patient was discharged from the hospital after a stay of 12 days, able to mobilise with residual weakness predominantly in his hands and feet. he chose to go straight home rather than stay in intermediate care. he was reviewed in the neurology clinic 2 weeks after discharge. power was restored except for mrc grade 4+/5 for finger extension and abduction in his non-dominant right hand, 3/5 for the left great toe dorsiflexion and 4+/5 for dorsiflexion of the left toes. he was able to stand on his toes but not on his heels, and walking was mildly affected. reflexes were now present and there remained no sensory signs. he was able to return to work 6 weeks after admission, but remained affected with intermittent chest pain and shortness of breath on going upstairs. guillain-barré syndrome is preceded by infection or other immune stimulus such as vaccination which induces an autoimmune response targeting the nervous system, 1 in this case the spinal roots and peripheral nerves. it is characterised by progressive weakness and areflexia, with pain preceding weakness in one-third of adult patients. 2 subtypes include demyelinating types, in which the affected myelin sheath causes aberrant conduction, and the axonal forms affecting the axons themselves. 3 this case highlights the difficulty of diagnosing guillain-barré syndrome as a cause of subacute weakness, when in a typical district general hospital covering 400 000 people we might expect 4-8 cases per year (1-2 per 100 000 population per year). the patient presented to the hospital three times before a diagnosis of guillain-barré syndrome was considered. there was neither facial weakness nor spinal pain to point towards the diagnosis. also highlighted is that evaluation of weakness based on loss of function can be more sensitive than physical examination: no lower limb weakness was identified on examination despite the patient having difficulty standing from a chair. it is invaluable to record one or two reflexes in both the upper and lower limbs in any patient with subjective weakness to alert the clinician to a potential upper or lower motor neurone disorder and as a baseline for future examination. recording of reflexes on prior attendances may have shortened the time to diagnosis. this case raises the issue of whether the concurrent covid-19 infection was a coincidence or could have been related to the guillain-barré syndrome. covid-19 is a disease caused by a newly emergent virus species of the betacoronavirus genus, other species of which have caused the common cold, severe acute respiratory syndrome (sars) and middle east respiratory syndrome (mers). the new virus has been called severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and has been identified as the cause of an outbreak of a respiratory illness that originated in wuhan city, hubei province, china, in december 2019. 4 the who named the disease 'coronavirus disease 2019' (covid-19) and in march 2020 declared the covid-19 outbreak a pandemic. sars-cov-2 has similar characteristics to sars and mers coronaviruses. 5 species of betacoronavirus genus are known to be potentially neuroinvasive. previously mers was found to be associated with guillain-barré syndrome in two patients. 6 neurological manifestations associated with covid-19 include stroke, impaired consciousness and encephalopathy. 7 there have been at least 12 cases reported in the literature as of 2 may 2020 linking guillain-barré syndrome with sars-cov-2 (covid-19). [8] [9] [10] [11] [12] [13] [14] [15] as with our patient, four of these cases had signs of guillain-barré syndrome at initial presentation. 8 14-17 uk-wide surveillance via notification portals identified three confirmed cases of guillain-barré syndrome reported from 2 april 2020 to 26 april 2020, of which this patient was one. 18 our patient developed signs of guillain-barré syndrome before covid-19 respiratory symptoms started on day 4 of weakness. the question is posed whether this could be a parainfectious phenomenon, due to direct neuroinvasion by the virus. or could it be postinfectious with the incubation period for respiratory symptoms overlapping that for immune-mediated neurological symptoms? guillain-barré syndrome usually follows an immune stimulus from day 1 to 4 weeks later. possible causes of the new disease case presented here are the bowel disturbance in prague 4 weeks before and the sars-cov-2 infection. it is intriguing that the length of the presymptomatic phase of sars-cov-2 before respiratory symptoms (the incubation period) is up to at least 14 days. first of all i would like to thank all nurses and doctors who took care of me in southend hospital. the whole experience was scary because obviously nothing like this has ever happened to me. i agree with what's said in the report regarding accepting and examining patients coming to a&e -i was only admitted and treated only the 3rd time i came to hospital. however, the care i received after that was brilliant and it was re-assuring to hear stories from a doctor who had suffered gbs before. he told me everything will be as it was. this was a stressful time for me and my family and i am still not 100% recovered, but i have started to go to work (around 1.5 months after first symptoms) and am expected to make full recovery. thank you again. ► consideration of function as well as physical examination of power to determine the location of weakness are important. ► examining reflexes and checking for plantar responses in any patient with weakness are also important. ► with the backdrop of the covid-19 pandemic, the presence of a concurrent covid-19 infection needs to be considered in patients presenting with symptoms and signs of guillain-barré syndrome. ► if neurological manifestations of covid-19 infection could appear before respiratory symptoms, it would be of utmost importance to use effective personal protective equipment, in particular for aerosol-generating procedures such as spirometry, in patients presenting with guillain-barré syndrome. guillain-barré syndrome guillain-barré syndrome mimics and chameleons in guillain-barré and miller fisher syndromes identification of a novel coronavirus causing severe pneumonia in human: a descriptive study novel coronavirus (covid-19) outbreak: a review of the current literature neurological complications during treatment of middle east respiratory syndrome neurologic manifestations of hospitalized patients with coronavirus disease neurological manifestations of covid-19 (sars-cov-2): a review guillain-barré syndrome associated with sars-cov-2 infection: causality or coincidence? guillain barre syndrome associated with covid-19 infection: a case report guillain-barré syndrome associated with sars-cov-2 coronavirus statement. malton, north yorkshire encephalitis society beijing hospital confirms nervous system infections by novel coronavirus covid-19 may induce guillain-barré syndrome guillain-barré syndrome following covid-19: new infection, old complication? guillain-barré syndrome associated with sars-cov-2 infection guillain-barré syndrome related to covid-19 infection neurological and neuropsychiatric complications of covid-19 in 153 patients: a uk-wide surveillance study the authors thank dr sara sotoudeh-nya, consultant in key: cord-315288-fcx4q6mp authors: hussain, mohammed hassan; siddiqui, saad; mahmood, sara; valsamakis, theodoros title: tracheal swab from front of neck airway for sars-cov-2; a bronchial foreign body date: 2020-08-27 journal: bmj case rep doi: 10.1136/bcr-2020-237787 sha: doc_id: 315288 cord_uid: fcx4q6mp we report the case of a bronchial foreign body, following a tracheostomy site swab for sars-cov-2, aiming to raise awareness and vigilance. a qualified nurse was performing a routine sars-cov-2 swab on a 51-year-old woman, fitted with a tracheostomy in the recent past following a craniotomy. this was part of the discharging protocol to a nursing home. during the sampling, part of the swab stylet snapped and was inadvertently dropped through the tracheostomy site. initial ct imaging was reported as showing no signs of a foreign body but some inflammatory changes. bedside flexible endoscopy through the tracheostomy site revealed the swab in a right lobar bronchus. this was subsequently removed by flexible bronchoscopy. this case highlights the need for clear guidance on how samples for sars-cov-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. we report the case of a bronchial foreign body, following a tracheostomy site swab for sars-cov-2, aiming to raise awareness and vigilance. a qualified nurse was performing a routine sars-cov-2 swab on a 51-year-old woman, fitted with a tracheostomy in the recent past following a craniotomy. this was part of the discharging protocol to a nursing home. during the sampling, part of the swab stylet snapped and was inadvertently dropped through the tracheostomy site. initial ct imaging was reported as showing no signs of a foreign body but some inflammatory changes. bedside flexible endoscopy through the tracheostomy site revealed the swab in a right lobar bronchus. this was subsequently removed by flexible bronchoscopy. this case highlights the need for clear guidance on how samples for sars-cov-2 are taken from patients with front of neck airways (laryngectomy/tracheοstomy) and the potential pitfalls involved. the novel covid-19, sars-cov-2, is currently a pandemic. while in most cases, only a mild illness ensues, severe disease can be complicated by acute respiratory distress syndrome, septic shock, cardiac injury and death. 1 the risk of spread of this virus has led to stringent measures being implemented both in hospitals and society in general. at our university, all admissions are being swabbed for sars-cov-2. real-time reverse transcriptase pcr (rrt-pcr) of a combined oropharyngeal and nasopharyngeal swab is used to confirm diagnosis. patients with front of neck airways, either in the form of a laryngectomy or tracheostomy stoma site, present a challenge in terms of testing for sars-cov-2. there is no current clear guidance on how these patients should be tested. in addition, questions remain around whether the exclusion of the upper airway in laryngectomy patients affects the sensitivity of rrt-pcr testing in nasopharyngeal and oropharyngeal swabs. the potential pitfalls of taking a swab from a tracheostomy site are highlighted clearly by this case. a 51-year-old woman presented with temporal lobe thrombosis complicated by haemorrhagic transformation. this required neurosurgical intervention in the form of a craniotomy and evacuation of haematoma and she was transferred to our institute with a tracheostomy tube in situ. prior to discharge to a nursing home, a swab was taken to test for sars-cov-2, as per protocol prior to transfer. a mucosal swab was attempted through the trachesotomy tube. during this process, the nurse felt the swab stylet snap with the distal end falling into the trachea, although she was not certain. the patient became momentarily unsettled with her oxygen requirements increasing to 4 l/min from 2 l/min. she quickly returned to her normal, with her oxygen saturation levels maintained at baseline levels of 88%-92% on 2 l/min of o 2 , considering her background of chronic obstructive pulmonary disease. the culture swab used at our institute is a sigma virocult, a small vial with 1.0 ml medium and a standard sigma swab (figure 1). the bud type is cellular foam. the swab's stylet length is 15 cm and this breaks into two parts with the distal part (bud end) inserted in the vial. a plain radiograph was performed (figure 2), which was unremarkable. a ct scan was then performed and initially reported as showing no signs of a foreign body, but rather signs of infective changes in the posterior segment of the right lower lobe. later, an addendum report of the ct scan raised suspicion of a foreign body as subtle signs were identified (figures 3-5). a decision had been made for a flexible endoscopy, a high-risk procedure in sars-cov-2 era, to take place. this was performed through the tracheostomy site using a disposable flexible ambu ascope 4 rhinolaryngo slim device. the swab was identified on the right side, in a lobar bronchus (video 1) and was subsequently removed by flexible bronchoscopy. accurate and prompt detection of sars-cov-2 is essential to controlling outbreaks both in hospitals and in the community. diagnosis is usually confirmed by rrt-pcr of combined nasopharyngeal and oropharyngeal swabs. 2 3 there have been recent studies into whether the sars-cov-2 virus can be detected from other tissue samples. one study which included 1070 tissue samples from 205 patients with covid-19 found that brochoalveolar lavage fluid showed the highest positive rates (93%). this was compared with 63% for nasal swabs and 32% for pharyngeal swabs. 3 there is currently no guidance on how patients with front of neck airways should be tested. the question arises as to how the biodistribution of sars-cov-2 is affected in these patients, especially in laryngectomy patients where there is an exclusion of the upper airway. the us's centers for disease control and prevention recommends a lower respiratory aspirate in special clinical circumstances such as patients on mechanical ventilation. 4 the national tracheostomy safety project's statement on considerations for trachestomy reiterates that tracheal aspirates are preferable to mucosal swabs but does not outline when tracheal aspirates should be taken. 5 the above case highlights the potential dangers of taking a mucosal swab from a trachesotomy site. hightened concerns around sars-cov-2 and wearing full personal protective equipment increase the probability of human error occurring. there is a need for clear guidance on how to test patients with front of neck airways for sars-cov-2. this will be dependent on two main factors. first, how a front of neck airway affects the biodistribution of sars-cov-2 in the mucosa of the oropharynx and nasopharynx and second, understanding of the risk of increased aerosolisation associated with taking any sample from a tracheostomy site. further studies are needed to shed light on the above. contributors mhh: conception of idea and drafting of the manuscript. ss and sm: literature review and drafting the manuscript. tv: review of the final manuscript. funding university hospitals of leicester nhs trust (866108). competing interests none declared. provenance and peer review not commissioned; externally peer reviewed. this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. mohammed hassan hussain http:// orcid. org/ 0000-0002-5988-3405 clinical management of severe acute respiratory infection (sari) when covid-19 disease is suspected: interim guidance clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china detection of sars-cov-2 in different types of clinical specimens interim guidelines for collecting, handling, and testing clinical specimens from persons under investigation (puis) for coronavirus disease ntsp. ntsp considerations for tracheostomy in the covid-19 outbreak ► there is lack of guidance on how to test patients with front of neck airway for sars-cov-2. ► mucosal tracheal swab through a tracheostomy tube carries an increased risk and appropriately designed sampling devices, which among else would be radiopaque, should be used. ► despite the sensitivity of a tracheal aspirate being higher than that of an oropharyngeal/nasopharyngeal swab, further research is needed to clarify the increased risk of aerosolisation in this cohort of patients. ► ct imaging cannot always exclude a foreign body bronchus and communicating detailed clinical information to radiology colleagues is, as always, of paramount importance if there is suspicion of a foreign body. ► visualisation of the airway should always be considered as the examination of choice in the absence of any contraindications.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-296619-uhhndp0a authors: kondo, yuki; miyazaki, shinichi; yamashita, ryo; ikeda, takuya title: coinfection with sars-cov-2 and influenza a virus date: 2020-07-01 journal: bmj case rep doi: 10.1136/bcr-2020-236812 sha: doc_id: 296619 cord_uid: uhhndp0a since december 2019, coronavirus disease 2019 (covid-19) has been an international public health emergency. the possibility of covid-19 should be considered primarily in patients with new-onset fever or respiratory tract symptoms. however, these symptoms can occur with other viral respiratory illnesses. we reported a case of severe acute respiratory syndrome coronavirus 2 and influenza a virus coinfection. during the epidemic, the possibility of covid-19 should be considered regardless of positive findings for other pathogens. since december 2019, coronavirus disease 2019 (covid-19) has been an international public health emergency. the possibility of covid-19 should be considered primarily in patients with new-onset fever or respiratory tract symptoms. however, these symptoms can occur with other viral respiratory illnesses. we reported a case of severe acute respiratory syndrome coronavirus 2 and influenza a virus coinfection. during the epidemic, the possibility of covid-19 should be considered regardless of positive findings for other pathogens. in late 2019, a novel coronavirus, known as severe acute respiratory syndrome coronavirus 2 (sars-cov-2), was identified as the cause of an outbreak of acute respiratory illness in wuhan, china. since then, there has been a rapid spread of the virus, leading to a global pandemic of coronavirus disease 2019 (covid-19). we report a case of coinfection with sars-cov-2 and influenza a virus in a patient with pneumonia in japan. the patient with both covid-19 and influenza virus infection presented similar clinical characteristics with covid-19 only. during the epidemic, the possibility of covid-19 should be considered regardless of positive findings for other pathogens. in april 2020, a 57-year-old japanese man was admitted to our hospital with an 8-day history of fever and non-productive cough. six days before admission, the patient presented first to general practitioners. the patient had a positive result for influenza a from a nasopharyngeal swab test. the patient was prescribed with laninamivir, but his symptoms did not improve. two days before admission, the patient was referred to our hospital for a prolonged fever. anteroposterior chest radiograph (figure 1a) found ground-glass opacities (ggo) in the left lung and he was treated with garenoxacin. later, real-time reverse transcription-polymerase chain reaction (rrt-pcr) of his nasopharyngeal swab returned positive for sars-cov-2. his medical history included vasospastic angina and diabetes mellitus. his medications were sitagliptin and miglitol. he worked as customer service in a restaurant. there was no history of smoking, travel or any contact with sick people. on admission, the patient reported of shortness of breath, anosmia and ageusia. vital signs were as follows: temperature, 38.8°c; blood pressure 131/74, mm hg; heart rate, 80 beats/min; respiratory rate, 20 breaths/min; and oxygen saturation, 91% on room air with desaturation on minimal exertion. complete blood count revealed white blood cells, 8.3×10 9 /l (neutrophils, 86%; lymphocytes, 8%; and monocytes, 6%); haemoglobin 144 g/l; mean corpuscular volume, 96 fl; and platelets, 199×10 9 /l. serum laboratory test results were as follows: total protein, 6.5 g/dl; albumin, 3.1 g/dl; total bilirubin, 0.6 mg/dl; aspartate aminotransferase, 103 iu/l; alanine transaminase, 161 iu/l; g-glutamyl transferase, 114 iu/l; lactate dehydrogenase, 416 iu/l; blood urea nitrogen, 11 mg/dl; creatinine, 0.8 mg/dl; sodium, 136 mmol/l; potassium, 4.6 mmol/l; chloride, 97 mmol/l; glucose, 231 mg/dl; haemoglobin a1c, 7.2%; ferritin, 1695 ng/ml; c-reactive protein, 15.7 mg/dl; and procalcitonin,<0.1 ng/ml. hepatitis b surface antigen and anti-hepatitis c virus were negative. an ecg was normal. anteroposterior chest radiography (figure 1b) revealed consolidation in the left lung. further evaluation with ct scanning of the chest (figure 2) found peripheral, bilateral, ggo with consolidation and visible intralobular lines (crazypaving appearance). sputum cultures for bacteria, fungus and acid-fast bacilli were all negative. initial considerations for this patient who presented acutely with fever and cough include infection with a common virus (rhinoviruses, non-sars-cov-2 coronaviruses and influenza virus) and communityacquired pneumonia. the rapid antigen testing and his clinical course make influenza pneumonia likely. owing to the sars-cov-2 outbreak in japan, covid-19 also needs to be considered. ciclesonide inhaler (200 μg two times per day for 14 days), favipiravir (1800 mg two times per day at day 1, followed by 800 mg two times per day for a total duration of 14 days) and broad-spectrum antibiotics (meropenem and azithromycin) were initiated. soon after hospitalisation, the patient developed progressive hypoxaemia (oxygen saturation of 91% on 2 l/min via nasal cannula). the fever continued for the first 4 days of hospitalisation, but subsequently abated. at day 7 of hospitalisation, the new disease patient's dyspnoea and hypoxaemia improved. according to discharge criteria for confirmed covid-19 cases in japan (2 negative rrt-pcr tests from nasopharyngeal swabs at 24 hours interval and clinical improvement of signs and symptoms), he was discharged home 4 weeks after hospitalisation. fortunately, because of the small number of patients with covid-19 in our area, the patient was placed in a single-patient, negative-pressure room. all healthcare workers who enter the room of the patient wore personal protective equipment. coinfection with sars-cov-2 and other respiratory viruses has been described, but the reported frequency is variable. among 5700 patients hospitalised with covid-19 in new york city, 42 patients (2.1%) had respiratory virus coinfection with enterovirus/rhinovirus (22/42), other coronavirus (7/42), respiratory syncytial virus (4/42), parainfluenza 3 (3/42), human metapneumovirus (2/42) and influenza a virus (1/42). 1 in northern california, the coinfection rate between sars-cov-2 and other respiratory pathogens was 20.7%. 2 the coinfections were enterovirus/rhinovirus (6.9%), respiratory syncytial virus (5.2%), other coronaviridae (4.3%), human metapneumovirus (1.7%) and influenza a virus (0.9%). there was no significant difference in the rates of sars-cov-2 infection in patients with and without other pathogens. the presence of a non-sars-cov-2 pathogen may not provide reassurance that a patient does not also have sars-cov-2. in wuhan, china, 5 of 115 patients (4.35%) confirmed with covid-19 were diagnosed with influenza virus infection, with 3 cases being of influenza a and 2 cases of influenza b. 3 the clinical characteristics of patients with both covid-19 and influenza virus infection were similar to those of covid-19 cases. now, the national institutes of health covid-19 treatment guidelines recommend remdesivir for hospitalised patients with severe covid-19. 4 however, at that time, no drug had been proven to be safe and effective for treating covid-19. therefore, with the consent of the patient, off-label use of ciclesonide and favipiravir was administered. in vitro studies have demonstrated that ciclesonide has good antiviral activity against sars-cov-2. 5 although the clinical effectiveness of ciclesonide in the treatment of covid-19 was reported in some cases, 6 there is no clinical trial to evaluate its antiviral activity in patients with covid-19. favipiravir is an rna polymerase inhibitor that is available in some asian countries for the treatment of influenza. in an openlabel non-randomised control study, favipiravir was compared with lopinavir/ritonavir for the treatment of non-severe covid-19. 7 a shorter viral clearance time was found for favipiravir than lopinavir/ritonavir (median, 4 vs 11 days, p<0.001). at day 14 after treatment, the improvement rates on chest ct with favipiravir were significantly higher than lopinavir/ritonavir (91.4% vs 62.2 %, p=0.004). these data support further investigation with randomised clinical trials on the efficacy of favipiravir for the treatment of covid-19. ► there was no significant difference in rates of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in patients with and without other pathogens. ► sars-cov-2 mimics the clinical characteristics of the influenza virus. ► during the epidemic, the possibility of covid-19 should be considered regardless of positive findings for other pathogens. contributors yk and sm wrote the initial manuscript and edited it. ry and ti supervised and edited the manuscript to its completion. all authors read and approved the final version of the manuscript. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. chest radiograph 2 days before admission (a) and on admission (b). chest ct on admission. presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area rates of co-infection between sars-cov-2 and other respiratory pathogens the clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in wuhan national institutes of health (nih). coronavirus disease 2019 (covid-19) treatment guidelines identification of antiviral drug candidates against sars-cov-2 from fda-approved drugs therapeutic potential of ciclesonide inahalation for covid-19 pneumonia: report of three cases experimental treatment with favipiravir for covid-19: an open-label control study competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. shinichi miyazaki http:// orcid. org/ 0000-0002-6700-7675copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-259108-16lqa84n authors: gananandan, kohilan; sacks, benjamin; ewing, iain title: guttate psoriasis secondary to covid-19 date: 2020-08-11 journal: bmj case rep doi: 10.1136/bcr-2020-237367 sha: doc_id: 259108 cord_uid: 16lqa84n nan a 38-year-old man presented with symptoms of fever and dry cough. there was a past medical history of chronic plaque psoriasis with a single active psoriatic plaque affecting the lateral aspect of the right ankle. the patient was using no regular medication and no topical therapy for psoriasis at the time of presentation with respiratory symptoms. there were no throat symptoms and pharyngeal examination was normal. severe acute respiratory syndrome coronavirus 2 (sars-cov2) rna was detected from a nasopharyngeal swab confirming covid-19 infection. at day 6 following the onset of fever, multiple erythematous lesions began to form inferior to the knee on the anterior and lateral aspect of the right lower limb. at day 22 the patient sought a dermatological opinion as these lesions had failed to improve. on examination there were multiple drop-like well circumscribed salmon pink erythematous papules with a fine scale, measuring between 4 and 12 mm in size, consistent with guttate psoriasis (figure 1). blood tests showed igg positivity for sars-cov2, with otherwise normal full blood count, c-reactive protein and routine biochemistry. antistreptolysin o titre was negative at <200 iu/ ml. treatment was commenced with topical readily diluted betamethasone 0.025% cream applied two times per day. there was significant clinical improvement on review after 2 weeks, with no new lesions and regression of those previously identified (figure 2). guttate psoriasis is known to occur after acute infection. it is associated with genetic and i initially experienced only mild symptoms of covid-19 and was recovering in self-isolation. almost a week into the illness i began to develop a new rash on my right leg that spread quite rapidly over the next few days. i have a previous history of psoriasis, which had been stable for many years so despite being a practicing physician, i did not immediately link the new rash with this problem. things continued to get worse over the next 2 weeks so i sought an urgent dermatology consultation. the rash was recognised as a flare of guttate psoriasis and i was relieved that it responded so quickly to betamethasone cream. now, around a month down the line, things are much better and my skin has almost healed. when i looked up covid-19 as a cause for guttate psoriasis, i realised this had not been previously reported, so i was keen to collaborate as a co-author to report this new association. environmental factors, and usually arises in children or younger adults. 1 it is classically associated with streptococcal infection, 2 although respiratory virus infection can also trigger psoriatic flares in the absence of concurrent streptococcal infection. 3 a possible mechanism for viral infection leading to psoriatic flare is dysregulation of innate immune response following stimulation of toll-like receptor 3 by viral rna leading to production of pathogenic cytokines/chemokines il-36-γ and cxcl8. 3 this is the first case reported of an acute guttate flare of chronic psoriasis secondary to confirmed covid-19 infection. guttate psoriasis is known to have a better prognosis than other types of psoriasis and rapid involution with long-term remission is common. 4 the quality of evidence for treatment of guttate psoriasis is very low with an absence of trials assessing the efficacy and safety of phototherapy, topical or systemic drugs. 1 we observed rapid induction of remission with readily diluted betamethasone 0.025% cream. non-antistreptococcal interventions for acute guttate psoriasis or an acute guttate flare of chronic psoriasis the role of streptococcal infection in the initiation of guttate psoriasis respiratory virus infection triggers acute psoriasis flares across different clinical subtypes and genetic backgrounds clinical course of guttate psoriasis: long-term followup study contributors kg assessed the patient and helped to draft the manuscript. bs helped to draft the manuscript. ie, the patient, took the clinical photographs, wrote the patient's perspective and revised the manuscript. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. iain ewing http:// orcid. org/ 0000-0002-7903-5243learning points ► guttate psoriasis manifests as multiple drop-like well circumscribed erythematous papules and is commonly associated with acute, particularly streptococcal, infection. ► severe acute respiratory syndrome coronavirus 2 was identified as the infective precipitant in this case and further such cases may emerge as we learn more about the clinical manifestations of the covid-19 illness. ► high-quality evidence for treatment of guttate psoriasis is lacking, but the prognosis is good and rapid involution is common.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-333998-z2zahfv9 authors: taxbro, knut; kahlow, hannes; wulcan, hannes; fornarve, anna title: rhabdomyolysis and acute kidney injury in severe covid-19 infection date: 2020-09-02 journal: bmj case rep doi: 10.1136/bcr-2020-237616 sha: doc_id: 333998 cord_uid: z2zahfv9 we report the case of a 38-year-old man who presented to the emergency department with fever, myalgia, nausea, vomiting, dry cough, breathlessness and abdominal pain. he was admitted due to hypoxaemia and was diagnosed with sars-cov-2 and was subsequently referred to the intensive care unit for intubation and mechanical ventilation. severe rhabdomyolysis and acute kidney injury developed 4 days later and were suspected after noticing discolouration of the urine and a marked increase in plasma myoglobin levels. treatment included hydration, forced diuresis and continuous renal replacement therapy. in addition to the coronavirus disease acute respiratory distress syndrome, he was diagnosed with possible sars-cov-2-induced myositis with severe rhabdomyolysis and kidney failure. the patient survived and was discharged from intensive care after 12 days, returning home 23 days after hospitalisation, fully mobilised with a partially restored kidney function. currently, there is an unprecedented surge in the demand for intensive care resources throughout the world due to the covid-19 pandemic. 1 2 little is known about rhabdomyolysis and acute kidney injury (aki) in the context of the covid-19 infection in the intensive care setting. 3 4 recent reports suggest that aki during covid-19 infection could be associated with increased mortality. 5 due to a scarcity of reports available on the subject, we decided to present the symptoms, laboratory findings, clinical course and treatment of a patient in intensive care who developed severe rhabdomyolysis and aki during the course of the covid-19 infection. a 38-year-old man with type 2 diabetes, gout and mild obesity presented to the emergency department with a 1-week history of fever, myalgia, nausea, vomiting, dry cough, breathlessness and abdominal pain. he was brought in by ambulance but was conscious. at the time of admission, his oxygen saturation was 91% and other vital signs were normal. the suspicion of sars-cov-2 infection was high at the time of admission due to the presence of the classic symptoms in combination with a history of potential sars-cov-2 exposure. the patient had no history of statin use, drug abuse, immobilisation or trauma (well-known causes of rhabdomyolysis) prior to admission. after laboratory verification of the sars-cov-2 diagnosis, the patient was transferred from a neighbouring hospital to the infectious diseases clinic. within 24 hours of admission, the patient's arterial oxygenation worsened, and he was admitted to the intensive care unit (icu) for further management. despite supplemental oxygen (15 l on reservoir mask), the respiratory rate remained high (40 per minute), and an arterial blood gas showed hypoxaemia (po 2 8.0 kpa (reference 11.1-14.4 kpa)) without hypercapnia (pco 2 5.1 (reference 4.6-6.0 kpa)). ct of the chest revealed extensive bilateral ground-glass opacities (figure 1.) following intubation and ventilation, his vital signs stabilised. cefotaxime was initiated at the time of hospital admission and was supplemented with metronidazole on day 5 due to a gingival infection. analgosedation was maintained with propofol, fentanyl and clonidine throughout. muscle relaxation was used only during the endotracheal intubation procedure. on day 4 in the icu, the urine became teacoloured, myoglobin levels gradually increased (from normal levels on admission to a peak level of >21 000 µg/l) and the kidney function deteriorated (lowest recorded relative glomerular filtration rate of 18 ml/min/1.73 m 2 ). the rhabdomyolysis was preceded by several days of very high body temperatures (39-40°c) unresponsive to treatment with paracetamol and active external cooling. continuous renal replacement therapy was initiated through a femoral central venous catheter on the fifth day and continued for 7 more days. the patient was treated for moderate acute respiratory distress syndrome (ards) and successfully weaned from the ventilator and extubated 12 days after hospitalisation. troponin t levels increased markedly on day 12 without signs of ecg abnormalities. myocarditis was suspected based on laboratory findings, but echocardiography revealed a normal heart function (ejection fraction >60%). intermittent haemodialysis following intensive care was not required, and the patient was discharged from the hospital after 23 days. several biochemical tests were performed throughout the intensive care period. see table 1 for an outline of key test results. the main differential diagnosis to the patient's rhabdomyolysis was an acute ischaemic event in the extremities. the patient was thoroughly assessed for findings that shed new light on the possible pathogenesis of a disease or an adverse effect signs and symptoms of arterial embolisation and limb ischaemia, but no such suspicion could be verified. in addition, there was serious concern regarding the sudden, unexpected and asymptomatic increase in troponin t levels (from 8 ng/l to 444 ng/l) on the days following icu discharge. on one hand, troponin t levels indicated significant myocardial damage, but diagnostic criteria for neither myocardial infarction nor perimyocarditis were fulfilled. on the other hand, troponin t levels may be falsely high in the setting of aki. the initial treatment of the patient's ards consisted of oxygen on a reservoir mask. in intensive care, endotracheal intubation followed sedation and muscle relaxation with ketamine and rocuronium, respectively. we used a lung-protective ventilation approach with a pressure-controlled mode. the patient was weaned from the ventilator using pressure-support ventilation. the patient received treatment against pulmonary and gingival infections using cefotaxime and metronidazole, respectively. throughout intensive care, nutritional support was provided both intravenously and through a nasogastric tube. when myoglobinaemia was diagnosed on the fourth day in the icu, an attempt was made to increase the diuresis to reduce the risk of aki. balanced crystalloids and albumin were administered together with furosemide, potassium canrenoate, spironolactone and mannitol. despite these efforts, plasma myoglobin and serum creatinine continued to increase and continuous venovenous haemodiafiltration was initiated on the fifth day and continued until discharge from the icu 7 days later. following discharge from the icu, the patient received physiotherapy and his muscular strength improved. on the day of the hospital discharge, the patient was completely mobile and cognitively intact with a relative glomerular filtration rate of 48 ml/min/1.73 m 2 . nine days after discharge, the kidney function had completely normalised. within 2 days of discharge from intensive care, levels of both troponin t and myoglobin rapidly normalised and testing was repeated. following the rapidly evolving novel disease of the covid-19 pandemic, new knowledge about the disease is being constantly unearthed. thus far, only a few reports on rhabdomyolysis and aki associated with covid-19 have been published. 3 4 early reports from china indicate that 25% of patients with covid-19 in critical care have aki. 6 although type 2 diabetes is common among patients hospitalised for covid-19, it does not appear to be an independent predictor for mortality or mechanical ventilation. 7 however, obesity is prevalent in critically ill patients with covid-19, and increasing body mass index is associated with an increased risk for death and mechanical ventilation. 7 rhabdomyolysis is characterised by the leakage of contents from the striped myocytes into the bloodstream. during massive rhabdomyolysis, aki and subsequent renal failure are a potentially dangerous complication, particularly in the intensive care setting where it is estimated that rhabdomyolysis accounts for 7% of all aki cases in the usa. 5 8 viral myositis and rhabdomyolysis have been associated with several viruses including the influenza a and b, coxsackie, epstein-barr, herpes simplex, parainfluenza, adeno, echo, cytomegalo, measles, varicella zoster, human immunodeficiency and dengue viruses. 8 the potential magnitude of the myositis and rhabdomyolysis caused by the sars-cov-2 virus is largely unknown. influenza a and b are the most commonly reported viruses associated with myositis. in a case series reported by the paediatric emergency department, viral myositis was a major cause of rhabdomyolysis. 9 the exact mechanism by which viruses cause muscle destruction has not been established, but two possible mechanisms have been proposed: first, muscular necrosis related to the potential direct viral invasion of myocytes and second, the toxic effect on myocytes caused by the host response (cytokine release and other immunological factors). 10 11 myoglobinuria is pathognomonic of rhabdomyolysis, and evidence suggests that myoglobin impairs the glomerular filtration through several mechanisms including intrarenal vasoconstriction, ischaemic tubule injury and tubular obstruction. 8 damage to the tubular structures is augmented by hypovolaemia and an acidic urine, both relevant to the intensive care setting. 12 treatment of rhabdomyolysis during ards is a delicate balancing act. on one hand, hydration and forced diuresis may limit kidney damage. on the other hand, overhydration could prove deleterious to pulmonary function and gas exchange. 13 thus, early detection, close monitoring and prompt treatment are key. therefore, findings that shed new light on the possible pathogenesis of a disease or an adverse effect we suggest regular screening of serum myoglobin levels in patients with covid-19 admitted to intensive care. contemporary guidelines offer weak evidence-based treatment recommendations to prevent rhabdomyolysis-induced aki. 14 the main recommendation of these guidelines includes early crystalloid-based fluid resuscitation. the routine use of diuretics, alkalinisation, mannitol, antioxidants and renal replacement therapy is not recommended. our case report is limited by the lack of a definite aetiology of the rhabdomyolysis other than previously suggested viral and host-response mechanisms. nevertheless, we believe that it is important to recognise that rhabdomyolysis could be an important complication of covid-19. further research designed to better understand the pathophysiological mechanisms behind covid-19 related rhabdomyolysis would be of great value. when i first became sick, symptoms were mild and it was like a common cold. then i experienced nausea, vomiting, and pain around my hips. after a few days at home my wife had to call for an ambulance. i was able to walk to the ambulance by myself and i remember asking the ambulance crew for some water. when the doctors told me i had corona i didn't get too worried since i am young and strong. suddenly, i required more oxygen and i had more difficulties breathing. when i came to the icu i was afraid and i didn't want to be put on the ventilator. just before they put me asleep i remember one of the doctors holding my hand telling me they would look after me, which gave me some peace of mind. when they woke me up, i got to talk with my family over the phone and that made me very happy. the hospital staff were like angels, i am very grateful that they took care of me so well. now, some weeks after i was discharged, i am working part time, and enjoying meeting people again. i am not as strong as i used to be, but i am improving every week. ► we recommend clinicians to screen for myoglobinaemia in all patients with covid-19 on admission and throughout the intensive care period. ► in the context of acute respiratory distress syndrome and pulmonary failure, the concept of hydration and forced diuresis as treatment options is likely to be undesirable. ► acute renal failure appears to be common in patients with covid-19 in intensive care, and rhabdomyolysis could be a contributing factor to this. care for critically ill patients with covid-19 critical care utilization for the covid-19 outbreak in lombardy, italy rhabdomyolysis as potential late complication associated with covid-19 rhabdomyolysis as a presentation of 2019 novel coronavirus disease kidney involvement in covid-19 and rationale for extracorporeal therapies patients with covid-19 in 19 icus in wuhan, china: a crosssectional study phenotypic characteristics and prognosis of inpatients with covid-19 and diabetes: the coronado study rhabdomyolysis and acute kidney injury acute pediatric rhabdomyolysis: causes and rates of renal failure severe rhabdomyolysis and acute renal failure following recent coxsackie b virus infection animal models of picornavirus-induced autoimmune disease: their possible relevance to human disease studies of mechanisms and protective maneuvers in myoglobinuric acute renal injury comparison of two fluidmanagement strategies in acute lung injury prevention of rhabdomyolysis-induced acute kidney injury -a dasaim/dsit clinical practice guideline the authors would like to thank www. editage. com for key: cord-337809-bxvgr6qg authors: xiong, yong; song, shihui; ye, guangming; wang, xinghuan title: family cluster of three recovered cases of pneumonia due to severe acute respiratory syndrome coronavirus 2 infection date: 2020-05-04 journal: bmj case rep doi: 10.1136/bcr-2020-235302 sha: doc_id: 337809 cord_uid: bxvgr6qg the coronavirus disease (covid-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) was first reported in wuhan, china, in late 2019 and has affected more than 1 270 000 people worldwide. the numbers of reported cases continue to rise and threaten global health. transmissions among family members are frequently observed, although the route of transmission is partially known. here we report three cases of sars-cov-2 infection within one family. sequencing of the s gene of the viral genome showed 100% identity among samples, suggesting that the same strain caused the infection. following treatment with oseltamivir and short-term methylprednisolone combined with symptomatic management, all three patients recovered within 3 weeks, as evidenced by the disappearance of their symptoms, clearance of pulmonary infiltrates and consecutive negative molecular diagnostic test findings. our observations suggest the importance of preventing family transmission and the efficacy of current integrated treatment for mild/moderate pneumonia in covid-19 cases. the coronavirus disease (covid-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2) was first reported in wuhan, china, in late 2019 and has affected more than 1 270 000 people worldwide. the numbers of reported cases continue to rise and threaten global health. transmissions among family members are frequently observed, although the route of transmission is partially known. here we report three cases of sars-cov-2 infection within one family. sequencing of the s gene of the viral genome showed 100% identity among samples, suggesting that the same strain caused the infection. following treatment with oseltamivir and short-term methylprednisolone combined with symptomatic management, all three patients recovered within 3 weeks, as evidenced by the disappearance of their symptoms, clearance of pulmonary infiltrates and consecutive negative molecular diagnostic test findings. our observations suggest the importance of preventing family transmission and the efficacy of current integrated treatment for mild/ moderate pneumonia in covid-19 cases. severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is the pathogen responsible for the ongoing outbreak of pneumonia in wuhan, china. since the first cluster of atypical pneumonia cases was reported on 31 december 2019, 1 the disease has spread with surprising speed. while much attention has been focused on viral transmission dynamics and the spectrum of clinical illness, these aspects are not yet completely understood. [2] [3] [4] [5] [6] [7] [8] this report describes the epidemiological and clinical features of coronavirus disease (covid-19) among three members of a family following sars-cov-2 infection. owing to the unavailability of effective vaccines for the prevention of sars-cov-2, most preventive measures aim to reduce the risk of infection. 9 despite several recommended drugs, including the combination of lopinavir/ritonavir, nelfinavir and interferon-beta-1b, effective treatment options are scarce. 2 hence, prevention of infection is of utmost importance. we provide evidence to support the increasing concerns regarding person-to-person transmission of sars-cov-2. on 10 and 11 january 2020, a family of three, comprising the father (65 years), the mother (61 years) and the son (38 years), were admitted to the department of infectious disease at the zhongnan hospital of wuhan university with symptoms of cough and fever. on 21 december 2019, the mother had started coughing with expectoration. five days later, the father also developed a cough; he developed fever 7 days prior to admission. he had a history of hypertension and coronary heart disease, for which he had received a stent. both had symptoms of restricted breathing. on 3 january 2020 (12 days after the mother's illness), the son developed a cough. prior to admission, all three patients experienced fatigue and intermittent fever (37.9℃-39.1℃) for at least 1 day (figure 1). they had no shortness of breath or chest pain. physical examination revealed some degree of tonsil enlargement in the father and the son. lung auscultation revealed rhonchi in the father and the mother. other examination findings were generally unremarkable. none of the patients had visited the huanan seafood wholesale market in wuhan or the surrounding area in the previous 2 weeks. they denied any contact with diagnosed patients with similar symptoms. on admission, haemograms revealed lymphocyte counts reduced by nearly 50% in the mother and near-to-low-normal in the father and the son. other parameters such as white cell count, neutrophil and blood platelet counts were near-to-low-normal, suggesting not only lymphopaenia but also a haematological regeneration abnormality following infection. moreover, all of these parameters doubled on discharge of the patients from the hospital. none of the patients had abnormal haemoglobin values. oxygen saturation values were normal. additional laboratory investigations in these three patients showed no abnormalities except for increased c reactive protein levels (table 1) . pneumonia was diagnosed based on chest ct scans. the mother's lung showed a peripheral lesion with increased intensity and bilateral patchy shadows in the outer zone of the lungs. numerous patchy or segmental ground-glass opacities were observed in both lungs of the father and the son. 10 the lung opacities started to clear after 10 days of hospitalisation (figure 2). rapid nucleic acid amplification tests for respiratory syncytial virus, adenovirus, influenza virus a new disease figure 1 body temperature (blue) and heart rate (red) values after hospitalisation. the temperature of all three patients decreased within 3-5 days. the mother experienced only occasional febrile episodes, while the son had moderate-to-high fever for 4 days after admission. (table 2) . the treatment during hospitalisation was largely supportive. the patients intermittently received supplemental oxygen through a nasal cannula at a rate of 2 l per minute. owing to the difficulties in early diagnosis, all three patients were initially treated for suspected influenza with 75 mg oseltamivir phosphate capsules two times per day for the first 5 days of hospitalisation. the patients received 80 mg of methylprednisolone sodium succinate per day for the first 3 days, followed by 40 mg per day during the following 3 days, and 20 mg per day for another 3 days before being discontinued. the father received methylprednisolone at a dose of 40 mg per day for 5 days and 20 mg per day for another 5 days. considering the possibility of bacterial coinfection, the mother and the father were administered amoxicillin sodiumflucloxacillin sodium (6 g, intravenous infusion every 12 hours) for 2 weeks. the son received ceftriaxone-tazobactam (2 g, intravenous infusion, every 12 hours) for 3 days, followed by biapenem (0.3 g, intravenous infusion every 8 hours) for another 9 days. additionally, the mother and the son were administered levofloxacin (0.4 g, intravenous infusion, daily) starting on admission day 6 until day 14. the father received moxifloxacin (0.4 g, intravenous infusion, daily) for 2 weeks starting on admission day 1. the fever disappeared in all three patients approximately 5-7 days following admission and their clinical conditions further improved thereafter. after approximately 3 weeks of hospitalisation, lung inflammation had largely resolved, as indicated by ct scans, and two consecutive throat swab samples tested negative for sars-cov-2 with the rt-pcr test performed for each new disease figure 2 chest ct scans of the three patients. the mother's lung shows a peripheral lesion with increased intensity and bilateral patchy shadows in the outer zones. multiple patchy or segmental ground-glass opacities were observed in both lungs of the father and the son. due to the initial shortage of testing kits for sars-cov-2, the cases were not diagnosed until 20 january 2020. throat swabs obtained from all three patients on admission day 9 tested positive. subsequently, throat swabs obtained from them on admission days 18 and 20 tested negative for sars-cov-2 (figure 1). the genetic sequences of the viral s gene from samples collected from each family member were identical (data not shown) to each other and also were 100% identical to the reported viral strain (whu01) currently spreading in wuhan. our results not only support human-to-human transmission but also suggest that close contact within families is a high-risk factor. effective intervention measures for the prevention of family transmission need to be adopted. ► severe acute respiratory syndrome coronavirus 2 transmission among family members was confirmed. ► the patients recovered after treatment with oseltamivir and methylprednisolone. ► prevention of family transmission is important. ► the current integrated treatment for mild/moderate pneumonia is effective in covid-19. world health organization. pneumonia of unknown cause china potential of large "first generation" human-to-human transmission of 2019-ncov epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study a familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster importation and human-to-human transmission of a novel coronavirus in vietnam transmission of 2019-ncov infection from an asymptomatic contact in germany early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia a novel coronavirus from patients with pneumonia in china potential inhibitors against 2019-ncov coronavirus m protease from clinically approved medicines clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china acknowledgements we thank all the doctors and nurses who cared for these three patients. the case report was written by yx and ss and edited by gy and xw.funding this study was funded by the medical science advancement program (clinical medicine) of wuhan university (grant number tflc2018002). patient consent for publication obtained. copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-276984-npgalqoz authors: dahl mathiasen, victor; jensen-fangel, søren; skov, karin; leth, steffen title: uneventful case of covid-19 in a kidney transplant recipient date: 2020-07-20 journal: bmj case rep doi: 10.1136/bcr-2020-237427 sha: doc_id: 276984 cord_uid: npgalqoz kidney transplant recipients have been reported at a particularly high risk of severe covid-19 illness due to chronic immunosuppression and coexisting conditions. yet, here we describe a remarkably mild case of covid-19 in a 62-year-old female who had a kidney transplantation 10 years earlier due to autosomal dominant polycystic kidney disease. the patient was admitted for 1 day; immunosuppressive therapy with tacrolimus and low-dose prednisolone was continued; and the patient recovered successfully without the use of antiviral agents or oxygen therapy. the case demonstrates that kidney transplant recipients are not necessarily severely affected by covid-19. withdrawal of immunosuppressive therapy could be associated with poorer outcomes and should not be implemented thoughtlessly. as of 1 july 2020, the novel severe acute respiratory syndrome coronavirus 2 (sars-cov-2) causing covid-19 has infected more than 11.4 million individuals, globally spreading across 188 countries. 1 while the numbers of covid-19 cases and deaths have increased vastly and rapidly, there is sparse evidence about its impact on transplant recipients. kidney transplant recipients have been reported at a particularly high risk of severe covid-19 illness due to chronic immunosuppression and coexisting conditions. 2 yet, here we describe and discuss a remarkably mild case of covid-19 in a patient with a kidney transplant. a 62-year-old female who had a kidney transplantation 10 years earlier due to autosomal dominant polycystic kidney disease was admitted to the department of nephrology with 2 days of dry cough, myalgia, fatigue and fever. she denied other complaints, including chest pain, dyspnoea, palpitations and a sore throat. there was no recent travel history or any known exposures to sars-cov-2. however, the husband had similar symptoms for 3 days. the patient had a medical history of hypertension, hypercholesterolaemia, obesity (body mass index approximately 33.5 kg/m 2 ) and recurring urinary tract infections treated with prophylactic with 400 mg pivmecillinam daily. kidney graft function was reduced with an estimated glomerular filtration rate of around 30 ml/min/1.73 m 2 , and she was on a maintenance immunosuppressive regimen with 5 mg prednisolone once a day and tacrolimus 4.5 mg two times per day, with a through level of 2.6-4.8 µg/l at presentation. mycophenolate mofetil was discontinued 6 months earlier due to the recurrent urinary tract infections. the posttransplantation period was complicated by severe diverticulitis resulting in proctosigmoidectomy and a temporary colostomy. on admission, the patient had a temperature of 38.6°c; the blood pressure was 147/90 mm hg; the heart rate was 77 beats/min; the respiratory rate was 18 breaths/min; and the oxygen saturation was 95% while she was breathing ambient air. physical examination was normal except from sparse peripheral oedemas of both legs. biochemistry was normal apart from lymphopenia (1.14×10 9 /l, reference range 1.30-3.50) and increased creatinine at usual level (174 µmol/l, reference range 45-90). chest radiograph was without infiltrates. a urinary dipstick showed discrete proteinuria (30-100 mg/ dl) and a nasopharyngeal swab tested negative for influenza. blood cultures were negative, and plasma was negative for cytomegalovirus, epstein-barr virus and bk polyomavirus dna using pcr. treatment with azathioprine 250 mg once a day for 5 days was initiated, and the patient was discharged the morning after admission with improvement of symptoms. fourteen days after admission, the patient still had discrete coughing and intermittent fever, and was referred to a covid-19 drive-in test unit for an oropharyngeal swab, which was positive for sars-cov-2 rna using pcr. as this was in the beginning of the pandemic, routine covid-19 testing was not widely implemented. subsequently, she was sent in self-isolation with unchanged immunosuppressive therapy. at recurrent phone-based follow-ups, she reported increased well-being and at 37 days after admission, she expressed total recovery. we present a case of mild covid-19 in a patient in immunosuppressive therapy due to kidney transplantation. the case demonstrates that kidney transplant recipients are not necessarily severely affected by covid-19 and warrants future studies new disease on the interaction between covid-19 and the immunocompromised host. on 17 march 2020, the first case of post-transplant covid-19 was reported in a 52-year-old chinese male kidney transplant recipient who recovered successfully. 3 the patient was discontinued on tacrolimus and mycophenolate mofetil, was reduced in dose of methylprednisolone (40 mg once a day), and treated with nebulised interferon-α and polyclonal intravenous immunoglobulin therapy. at day 9 of illness, oxygen therapy of 2 l/min was administered. throughout the course of disease, biochemistry showed more evident signs of infection although still discrete with c reactive protein of 54 mg/l (day 2) and white blood cell count 11.68×10 9 /l (day 11). in comparison, this patient was hospitalised for 13 days, while the patient in our case was only admitted for a night. to our knowledge, the patient was in good health at home a week after admission, similar to the patient in our case story. tacrolimus and prednisolone were continued in our patient, although recently published data show that immunosuppressive therapy is often discontinued in kidney transplant recipients. 4 in this study, immunosuppressive management included withdrawal of an antimetabolite among 86% (n=24/28) and of tacrolimus among 21% (n=6/28). the authors suggest that low levels of cd3, cd4 and cd8 could justify this withdrawal strategy. unfortunately, in our case, an extensive analysis of inflammatory biomarkers was not conducted. in addition, the data (n=36) suggest a very high early mortality among kidney transplant recipients with covid-19 of 28% at 3 weeks compared with 1%-5% in the overall population in the usa. 4 a similar case fatality rate of 27.8% has been reported for a heterogenous group of solid-organ transplant recipients with covid-19 in spain, also much higher than the overall population. 5 most patients in this study underwent temporary discontinuation or dose reduction of calcineurin inhibitors (55.6%, n=10/18), while 50% (n=9/18) had their antimetabolites reduced or withdrawn. an ongoing study identified 10 kidney transplant recipients with covid-19, of which 9 were hospitalised. 6 five were admitted to the intensive care unit and three patients, who required intubation, died. all hospitalised patients had their antimetabolite agent stopped. tacrolimus/sirolimus was discontinued in 30% (n=3/10). for comparison, 4% of 237 patients, in a large multicentre study, with any solid-organ transplant (n=87, kidney) and microbiologically confirmed influenza a, died at a median of 15 days after onset of symptoms. 7 as demonstrated by our case and preliminary data, covid-19 presents with a wide clinical spectrum, ranging from asymptomatic and subclinical to severe, life-threatening infection. similarly, the prognosis seems to vary considerable among the overall population and individual kidney transplant recipients, although data imply an overall high mortality in transplant recipients. [4] [5] [6] a cytokine storm triggered by sars-cov-2 has been proposed responsible for the high morbidity in covid-19, 8 and it could be speculated that withdrawal of antirejection therapy could be associated with an exacerbated systemic inflammatory response to viral infection. 4 immunosuppressive therapy was relatively modest in this case, while other risk factors favouring a severe course of covid-19, such as hypertension, chronic kidney disease and obesity, were present. 9 10 regardless, the importance of addressing sars-cov-2 infection in transplant recipients and management of immunosuppressive therapy in relation to ongoing infection seems evident. 11 so far, no significant differences between baseline immunosuppression in solid-organ transplants and covid-19 severity have been reported. 12 despite the massive quantity of covid-19 data and research worldwide, more and improved information to guide clinical management is urgently needed. larger studies should be conducted to clarify whether solid-organ transplant recipients are in fact at a higher risk of severe disease compared with immunocompetent hosts, to determine the interaction between covid-19 and the graft and to elucidate the impact of immunomodulatory therapy and antiviral agents. for now, a prudence concept should be applied with utmost precaution advised in terms of infection prevention and clinical management of solidorgan transplant recipients. case by case must be evaluated carefully and managed according to age, risk factors, severity of infection, immunosuppressive regimen, immune status and side effects. thoughts about my meeting with covid-19. one day, i had a high fever and contacted the nephrologist on duty. i was admitted and had blood samples taken among others. actually, i was okay… just a fever. the nephrologist did not see any reason to test for covid-19 as it was so early in the course, and also my temperature decreased the next morning. i was discharged! having a fluctuating fever, nausea, vomiting and immense fatigue is not the most interesting. i did not have trouble breathing or pneumonia at any point. i did, however, cough a lot and i just could not believe it kept on. i often thought, have i been infected with the virus after all? it disturbed me that my temperature remained high. as days went by, the nausea gradually disappeared, and the appetite returned. the fever stabilised. only first at this point, after 14 days of illness, i was tested positive. for weeks after covid-19, i was very fatigued, but now finally, i have again regained my strength. ► there is sparse evidence about the impact of severe acute respiratory syndrome coronavirus 2 on kidney transplant recipients. ► limited data suggest a very high early mortality in these patients. ► withdrawal of immunosuppressive therapy could be associated with poorer outcomes and should not be implemented thoughtlessly. ► each case must be evaluated and managed carefully by experts. covid-19 dashboard by the center for systems science and engineering a single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for sars-cov2 pneumonia successful recovery of covid-19 pneumonia in a renal transplant recipient with long-term immunosuppression covid-19 and kidney transplantation covid-19 in solid organ transplant recipients: a single-center case series from spain covid-19 in kidney transplant recipients outcomes from pandemic influenza a h1n1 infection in recipients of solid-organ transplants: a multicentre cohort study covid-19: consider cytokine storm syndromes and immunosuppression clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study prevalence of obesity among adult inpatients with covid-19 in france managing covid-19 in renal transplant recipients: a review of recent literature and case supporting corticosteroid-sparing immunosuppression covid-19 in solid organ transplant recipients: initial report from the us epicenter acknowledgements we want to thank professor henrik birn, md, dmsc, phd at key: cord-337878-hiylqqie authors: namasivayam, abirami; soe, than; palman, jason title: atypical case of covid-19 in a critically unwell 5-week old infant date: 2020-09-14 journal: bmj case rep doi: 10.1136/bcr-2020-237142 sha: doc_id: 337878 cord_uid: hiylqqie the effect of covid-19 by sars-cov-2 on the paediatric population remains an evolving mystery. early reports from china stated that children seem to be unharmed by its dangerous effects, yet more recently there has been evidence of a systemic inflammatory response in a small number of children who are affected. we discuss a 5-week-old male infant who presented atypically with severe covid-19 infection. to our knowledge, he is the youngest reported case in the uk to require mechanical ventilation and intensive care treatment as a direct result of covid-19 following horizontal transmission. this case has generated several learning points with regard to atypical presentations of covid-19 and identifying a potential cohort of ‘at risk’ infants. we also highlight a number of new challenges that have arisen for paediatricians and anaesthetists providing airway management for infants with sars-cov-2. the world has unfortunately entered into a new challenge by facing the global pandemic of covid-19. at the time of writing, more than 200 countries have been affected with over 16 million confirmed cases and over 650 000 deaths. 1 even 6 months from the first reported case there remain vast uncertainties surrounding the virus. there has been extensive evidence which highlights the discriminatory nature of covid-19. while the elderly, immunocompromised and black asian and minority ethnic community remain its prime victims; children seem to be largely spared by its effects. 2 why and how children have this tolerance are crucial unanswered questions. between december 2019 and february 2020, china reported a total of 31 211 cases of confirmed covid-19. 3 only nine of these cases were infants (aged 28 days to 1 year), none of whom required intensive care, mechanical ventilation or had severe complications. 3 choi et al reviewed the epidemiology and clinical presentation of coronavirus in children as of march 2020, reporting 2.4% (0-18 years) in china, 3.6% (6 months to 17 years) in singapore, 1.4% (0-18 years) in italy, 1% (0-9 years) in republic of korea and 2.8% (0-9 years) in australia. 4 a larger nationwide study investigating 134 paediatric cases across china reported that 76% cases had fever, 64.9% cases presented as acute upper respiratory tract infection, 26.9% as mild pneumonia and 1.5% cases were critical; unfortunately, the specific age groups and comorbidities were not reported. 4 5 the royal college of paediatric child health has recently released evidence of children responding to covid-19 with a systemic inflammatory response. 6 however, greater awareness and investigation for children with suspected infection is needed. we report the case of a 5-week-old male infant who presented atypically to the commonly described features and deteriorated rapidly in our district general hospital (dgh). we explore the learning points from this case. a 34-day-old 2.1 kg ex-premature male infant was brought to the paediatric emergency department (ped) with reduced feeding and lethargy; he was 37 +3 weeks corrected gestation at the time. he was born at 32 +4 weeks gestation via caesarean section due to maternal type 1 diabetes mellitus and was admitted to the neonatal unit for support of prematurity and respiratory distress. the antenatal history was unremarkable. he was the first child born to parents, both white caucasian. although maternal steroids were given, he required surfactant at 24 hours of age and mechanical ventilation for 12 hours before weaning to continuous positive airway pressure (cpap) for 4 days, and later high flow nasal cannula (hfnc). chest x-ray at day 1 of life is seen in figure 1 . he was off all respiratory support by day 17 of life and quickly established breastfeeding. he was treated with antibiotics for 48 hours with suspected sepsis. he was discharged home at day 22 of life. since being discharged from the neonatal intensive care unit (nicu), he had been breastfeeding and thriving well with no other concerns. his mother brought him to ped because he had not fed well over the last 12 hours and his activity levels were reduced. he had no fever, no increased work of breathing and no cough. on initial assessment, he was alert but quiet. his heart rate was 125 bpm, his respiratory rate was 26/min, his saturations were 80% and despite being fully dressed, he was hypothermic with an unrecordable axillary temperature. high flow facial oxygen was given which improved his oxygen saturations to above 97%. although his respiratory rate was reduced, there were no other clinical signs of respiratory distress-no grunting, no recessions and his chest was clear with good air entry. he was haemodynamically stable with capillary refill time under 2 s. intravenous access was obtained to deliver ceftriaxone and amoxicillin for suspected sepsis; his blood gas at this time showed a partially compensated respiratory acidosis (table 1) . during this period he remained alert but was particularly quiet with minimal response to the interventions being performed. shortly after achieving intravenous access, the infant unexpectedly became unresponsive and bradycardic with heart rate reducing to 40-50 bpm with minimal respiratory effort. effective bag valve mask (bvm) ventilation was established and an intravenous fluid bolus was given. the heart rate rapidly improved on warming with a bair hugger and warmed intravenous fluids. during rewarming he became increasingly alert and responsive, however, his respiratory effort gradually deteriorated with tachypnoea, grunting, nasal flaring and intercostal recession. chest auscultation remained clear, heart sounds were normal with palpable femoral pulses and no hepatomegaly. the decision for cpap escalated to mechanical ventilation as he then developed frequent apnoeas. his rapid clinical decline within a short time frame and a suspicious chest x-ray raised the likely possibility that this was all attributed to covid-19 (figure 2). as per national and local resuscitation guidelines, 7 8 minimal staff all wearing full personal protective equipment (ppe), were present during intubation. a size 3 cm endotracheal tube was used; however, ventilation was more difficult than anticipated reflecting a rapidly evolving acute respiratory distress syndrome (ards). to improve ventilation, the infant was mechanically ventilated using a bvm which maintained stable observations. haematological markers revealed thrombocytopenia; platelets 48×10 9 /l while the haemoglobin concentration was 134 g/l, white cell count 5.6×10 9 /l, neutrophils 1.7×10 9 /l and lymphocytes 3.3×10 9 /l. his renal function and electrolytes were normal; his albumin was low at 25 g/l with a raised alanine aminotransferase of 78 iu/l and raised c reactive protein (crp) of 23 mg/l. his clotting studies were normal. table 1 demonstrates his progressive blood gases. his initial chest x-ray showed bilateral consolidation of the lung parenchyma and the subsequent x-ray performed after intubation showed bilateral 'ground-glass infiltration'. the worsening radiological findings correlate to the clinical deterioration of the patient and illustrate evidence of evolving ards. his nose and throat swabs for coronavirus pcr returned after 24 hours as strongly positive for sars-cov-2 rna. the patient was transferred to a tertiary unit where he required high frequency oscillation ventilation for 48 hours with a trial of inhaled nitric oxide and intermittently kept in prone position. he was conventionally ventilated for a further 4 days before weaning to cpap and later hfnc; he was off respiratory support by day 11. he was given a 10-day course of remdesivir along with cefotaxime, clarithromycin and acyclovir and had been on ionotropic support via a peripherally inserted central catheter line. his echocardiogram was structurally normal with normal ventricular function. he unfortunately developed a femoral thrombus for which he remains on dalteparin. he has been discharged from hospital, is developing well and being regularly monitored by the local dgh. at present there are few reports of paediatric patients requiring intensive care support with confirmed covid-19. to the best of our knowledge, this is the youngest reported case of sars-cov-2 following horizontal transmission in the uk. on presentation to ped the patient had no cough or fever symptoms which have been extensively reported as common clinical manifestations of covid-19. 8 similarly, the distinguishing biochemical abnormalities associated with covid-19 positive patients, specifically leucopenia 9 and significantly elevated crp, 10 were not observed in our case. as noted in table 1, the initial blood gas of the infant demonstrates a mixed acidosis and metabolic alkalosis. a plausible explanation for this could be that the infant had been in respiratory distress prior to presentation. this may also account for his hypothermia, lethargy and subsequent apnoeas; all of which suggest some neurological involvement. this case demonstrates the need for vigilance in considering covid-19 infection in infants presenting with less discriminatory symptoms such as lethargy or reduced feeding. in adults, comorbidities such as cardiovascular disease, diabetes and hypertension are associated with significant morbidity when infected with covid-19. 9 it remains a challenge to identify the most vulnerable groups among children. dong et al report a case series of 2135 paediatric patients with confirmed and suspected coronavirus; infants (<1 year) were noted to be particularly vulnerable. thirteen cases were 'critical'-quickly progressing to ards±shock, encephalopathy, myocardial injury, heart failure, coagulation dysfunction and acute kidney injury-seven of whom were less than 1 year of age. 11 the authors did not report the patient's comorbidities. there is evidence that the respiratory tract of premature babies has an immature mucosal barrier with a reduced mucociliary clearance, increasing their vulnerability to pulmonary infections. 12 although our patient was corrected to 37 weeks at presentation, his prematurity may have contributed to the increased risk of contracting the virus and the cascading response that followed. hong et al hypothesised that the reason for the small number of infants affected by the virus was because of their low risk of unusual presentation of more common disease/injury exposure to the virus. 13 since the infant was discharged from the neonatal unit 12 days before presenting to the emergency department he was within the 2-14 day incubation period for covid-19. 14 15 we must therefore consider the possibility of exposure before discharge from the neonatal unit, especially since he had remained at home isolating with his parents following his discharge. however, it is also important to note that there is no substantive evidence for vertical transmission from covid-19 positive mothers to their baby, and therefore neonatal units are considered a low risk area to covid-19. 16 17 it would have been valuable to have identified sources of potential exposure with contact testing and tracing. it is unfortunate that at the time of presentation, the 'nhs test and trace' service had not been implemented in the uk and therefore the route of transmission and acquisition of covid-19 remains unsolved. covid-19 is highly contagious and there is a large concern for healthcare staff involved in airway management for patients with the virus. guidance released by the resuscitation council uk and cook et al is being used to maintain the safety of staff while performing high risk aerosol generating procedures including intubation 7 8 ; however, the guidance remains quite limited for infants. there are also challenging non-technical factors to consider when providing advanced airway management for an infant with suspected covid-19. these factors included designating the most appropriate person to carry out intubation, use of cuffed endotracheal tubes, the number and selection of health professions involved during intubation, and communication barriers with full ppe and designated contained areas for managing the patient. understanding the clinical course of covid-19 in the paediatric population is continually evolving. although cases of critically unwell infants remain uncommon, this particular group may be more vulnerable. an appreciation for early identification of subtle symptoms, such as reduced feeding, lethargy and hypoxia in the absence of respiratory distress, will enable prompt escalation of care and appropriate stabilisation. although there is no specific guidance on airway management for infants with suspected covid-19, it is important to keep up-to-date with local and national guidance to ensure patient and staff safety. further epidemiological reports will hopefully uncover the vast expanse of symptomology of the heterogenic covid-19 positive paediatric cohort and the optimal management of the virus. contributors an contributed to the concept, write up and literature search of the case as well has being involved in the patient's initial care. ts was the consultant involved in the patient's care. jp reviewed, revised and edited the manuscript. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. chest x-rays of the patient pre and post intubation 3.5 hours apart, showing the transition from bilateral consolidation to bilateral ground glass infiltration due to evolving ards. ards, acute respiratory distress syndrome. ► covid-19 may present as subtly as lethargy and poor feeding in infants. ► infants may present with hypoxia in the absence of respiratory distress. ► more understanding on the effects of covid-19 in infants, especially premature infants is required. world health organization. coronavirus disease (covid-19) situation report covid-19 virus and children: what do we know? novel coronavirus infection in hospitalized infants under 1 year of age in china epidemiology and clinical features of coronavirus disease 2019 in children royal college of paediatrics and child health. guidance-paediatric multisystem inflammatory syndrome temporally associated with covid resuscitation council uk statement on covid-19 in relation to cpr and resuscitation in paediatrics consensus guidelines for managing the airway in patients with covid -19 clinical, laboratory and imaging features of covid-19: a systematic review and meta-analysis hyperinflammatory shock in children during covid-19 pandemic covid-19 in children: an epidemiology study from china why are preterm newborns at increased risk of infection? clinical characteristics of novel coronavirus disease 2019 (covid-19) in newborns, infants and children the incubation period of coronavirus disease 2019 (covid-19) from publicly reported confirmed cases: estimation and application incubation period and other epidemiological characteristics of 2019 novel coronavirus infections with right truncation: a statistical analysis of publicly available case data clinical characteristics and intrauterine vertical transmission potential of covid-19 infection in nine pregnant women: a retrospective review of medical records coronavirus disease (covid-19) and neonate: what neonatologist need to know patient consent for publication parental/guardian consent obtained.provenance and peer review not commissioned; externally peer reviewed.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-276938-hv2ttwr8 authors: artru, florent; alberio, lorenzo; moradpour, darius; stalder, grégoire title: acute immune thrombocytopaenic purpura in a patient with covid-19 and decompensated cirrhosis date: 2020-07-07 journal: bmj case rep doi: 10.1136/bcr-2020-236815 sha: doc_id: 276938 cord_uid: hv2ttwr8 we report on a patient with coronavirus disease 2019 (covid-19) and decompensated cirrhosis who experienced a favourable outcome of severe immune thrombocytopaenic purpura (itp) after administration of intravenous immunoglobulin and high-dose dexamethasone. the present case suggests that it is reasonable to evoke itp in case of profound thrombocytopaenia in a patient with covid-19. we report on a patient with coronavirus disease 2019 (covid-19) and decompensated cirrhosis who experienced a favourable outcome of severe immune thrombocytopaenic purpura (itp) after administration of intravenous immunoglobulin and high-dose dexamethasone. the present case suggests that it is reasonable to evoke itp in case of profound thrombocytopaenia in a patient with covid-19. published data suggest that poor outcome of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection is related to an excessive inflammatory reaction. recent publication suggest poor outcomes in patients with coronavirus disease 2019 (covid-19) and pre-existing advanced chronic liver disease. only scarce information is available regarding the management of sars-cov-2-related haematological disorders. we report on a 38-year-old obese patient with decompensated cirrhosis (child-pugh c10) and iga nephropathy who was hospitalised on 1 april 2020 in the context of covid-19 documented by positive pcr for sars-cov-2 on nasopharyngeal swab. cirrhosis was due to alcoholic liver disease, likely aggravated by concomitant non-alcoholic steatohepatitis, and was complicated by refractory ascites since 4 months. during the 10 days preceding admission, the patient developed asthenia, fever and rapidly worsening cough associated with dyspnoea at rest. on admission, he was febrile at 39°c and had a respiratory rate of 35 per minute. the oxygen saturation was 85% while breathing ambient air and he required 6 l per minute of oxygen in the context of worsening pneumonia. chest x-ray showed the presence of bilateral peripheral airspace opacities. c reactive protein was 31 mg/l (normal range,<10 mg/l), procalcitonin 0.41 µg/l (normal range, 0.10-0.49 µg/l), ferritin 1120 µg/l (normal range, 12-300 µg/l) and d-dimers 7828 ng/ ml (normal range, <500 ng/l). the patient was treated with hydroxychloroquin (600 mg/day) and co-amoxicillin/clavulanic acid (4800 mg/day) during the first 4 days. laboratory tests performed over the next days showed a rapid decrease of platelet count from baseline values around 70 g/l (chronic moderate thrombocytopaenia due to liver disease and hypersplenism) to a nadir of 1 x10 9 /l (figure 1). because of severe epistaxis, platelet transfusions were administered, however with no response. a blood smear confirmed severe thrombocytopaenia and did not show any schistocytes; coagulation studies allowed to exclude disseminated intravascular coagulation (dic), anti-platelet factor 4/heparin antibodies were not detected, testing for viral hepatitis, hiv, cytomegalovirus, epstein-barr virus and varicella zoster virus was negative. hence, a diagnosis of likely sars-cov-2-related immune thrombocytopaenic purpura (itp) was retained. intravenous immunoglobulin (ivig) (0.4 g/kg per day for 5 days) and high-dose dexamethasone (40 mg/day for 4 days) were initiated, resulting in rapid improvement of platelet counts and cessation of epistaxis (figure 1). after a transient stabilisation, platelet counts dropped again slowly to 22 g/l on day 21. hence, a second cycle of dexamethasone (40 mg/day for 4 days) was administered and followed by a rapid increase in platelet counts to the patient's baseline values (75 g/l at day 36). of note, the patient unusual association of diseases/symptoms underwent three ascites taps. two of them were performed when platelet counts were <20 g/l, without any bleeding complication. the large volume paracenteses may have helped improving lung ventilation. the course of pneumonia was also favourable and liver as well as renal functions could be stabilised. the patient did not experience any bacterial superinfection. in line with a recent report, it is reasonable to evoke itp in case of profound thrombocytopaenia in a patient with covid-19. 1 indeed, the emergence of autoimmune diseases in the context of sars-cov-2 is increasingly reported. 2 the differential diagnosis of thrombocytopaenia in a cirrhotic patient with covid-19 includes splenic sequestration, consumption within large thrombi, dic and sepsis-induced thrombocytopaenia. indeed, severe sars-cov-2 infection is associated with coagulopathy, although thrombocytopaenia is usually moderate. 3 in this case, the kinetics of the onset of thrombocytopaenia, its depth, the absence of even a transient response to platelet transfusions, the stability of coagulation parameters and the response to treatment with ivig and dexamethasone provide reasonable evidence of an immune origin to thrombocytopaenia. 4 treatment with ivig and the two cycles of dexamethasone has likely resulted in improvement of platelet counts 4 that eventually returned to the baseline values of the patient. importantly, the patient also experienced a favourable course of covid-19 pneumonia. hence, one may speculate that ivig and dexamethasone had a beneficial impact on the excessive inflammatory reaction associated with sars-cov-2 infection, 5 contributing to the favourable clinical course of the pneumonia observed in our patient. of note, this outcome is remarkable also in light of recent data indicating an increased mortality from covid-19 in patients with pre-existing liver disease and, notably, cirrhosis. 6 however, more data are needed to validate this hypothesis and to assess the clinical course of covid-19 in patients with cirrhosis as well as the incidence of itp and the effects of its treatment in the setting of sars-cov-2 infection. immune thrombocytopenic purpura in a patient with covid-19 autoimmune and inflammatory diseases following covid-19 covid-19 and its implications for thrombosis and anticoagulation immune thrombocytopenia covid-19: consider cytokine storm syndromes and immunosuppression clinical characteristics and outcomes of covid-19 among patients with pre-existing liver disease in united states: a multi-center research network study contributors fa and gs conceived the study, performed the literature research and wrote the paper. la and dm wrote, commented and corrected the manuscript.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. grégoire stalder http:// orcid. org/ 0000-0002-0536-5418learning points ► in case of severe acute respiratory syndrome coronavirus 2 (sars-cov-2) and severe thrombocytopaenia, it is reasonable to consider a diagnosis of immune thrombocytopaenia (itp). ► treatment of itp in the context of coronavirus disease 2019 (covid-19) with high-dose dexamethasone and intravenous immunoglobulin (ivig) appears to be effective. ► treatment with high-dose dexamethasone and ivig may have promoted a favourable course of covid-19 in this decompensated cirrhotic patient.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-257691-oka9d03h authors: bogaert, kelly; christensen, kyrstin; cagliostro, matthew; ferrara, lauren title: contained aortic rupture in a term pregnant patient during the covid-19 pandemic date: 2020-09-15 journal: bmj case rep doi: 10.1136/bcr-2020-238370 sha: doc_id: 257691 cord_uid: oka9d03h aortic dissection and rupture is a rare occurrence in pregnant and postpartum patients. this case discusses the presentation and diagnosis of a patient with an acute contained thoracic aortic aneurysm rupture at 38 weeks of gestation, after presenting with throat pain and syncope during the covid-19 pandemic. the patient underwent emergent caesarean delivery for non-reassuring fetal heart tracing, following which continued syncope workup revealed an aortic aneurysm and pericardial effusion. diagnosis in this case was finalised with multimodality imaging, including transthoracic echocardiogram, and the patient underwent surgical aortic repair. aortic dissection and rupture is a rare occurrence in pregnant and postpartum patients. this case discusses the presentation and diagnosis of a patient with an acute contained thoracic aortic aneurysm rupture at 38 weeks of gestation, after presenting with throat pain and syncope during the covid-19 pandemic. the patient underwent emergent caesarean delivery for nonreassuring fetal heart tracing, following which continued syncope workup revealed an aortic aneurysm and pericardial effusion. diagnosis in this case was finalised with multimodality imaging, including transthoracic echocardiogram, and the patient underwent surgical aortic repair. aortic dissection and rupture are rare but lifethreatening conditions, particularly during pregnancy. most commonly, these conditions arise in the third trimester or postpartum period, with the most common cause of death being cardiac tamponade. 1 2 aortic dissections are stratified into two categories based on the stanford criteria, with type a involving the ascending aorta and type b not involving the ascending aorta. 3 type a aortic dissections are more common during pregnancy and postpartum, and can lead to a mortality rate as high as 50% if not treated surgically within 48 hours. [4] [5] [6] risk factors for aortic dissection include connective tissue disorders, such as marfan syndrome and loeys-dietz syndrome, congenital cardiovascular anomalies, such as bicuspid aortic valve and aortic coarctation, familial history of aortic dissection and chronic hypertension. 1 3 7 we present the case of a patient diagnosed with an acute aortic rupture at term during the covid-19 pandemic. while previous case reports have described the diagnosis and management of aortic dissection and rupture during pregnancy, this case uniquely describes the challenges of diagnosing aortic dissection and rupture during the covid-19 pandemic as well as the use of echocardiogram in determining this diagnosis. a 33-year-old female gravida 1 presented at 38 weeks of gestation to a hospital in queens, new york, after a syncopal episode. the patient had received routine prenatal care with a private physician, and her pregnancy thus far had been uncomplicated. she reported feeling well the day prior to presentation, but woke from sleep around 04:00 on the day of presentation with shortness of breath, throat pain and 'clamminess'. the patient's husband woke to her falling off the bed, having lost consciousness and subsequently hitting her head and abdomen. on waking, the patient endorsed dizziness, mild shortness of breath and throat pain. on arrival to labour and delivery triage, the patient was noted to have oligohydramnios on pelvic ultrasound with an amniotic fluid index of 1, and fetal tachycardia with minimal to moderate variability. the patient herself was tachycardic to 109 beats/ min with a blood pressure of 88/66 mm hg, vital signs that are considered within normal limits for a pregnant patient. the patient was given a bolus of intravenous fluids, and a covid-19 swab was sent in addition to standard inflammatory markers recommended in the work-up of covid-19. an ecg demonstrated sinus tachycardia with non-specific t-wave inversions in lead iii. a portable chest x-ray was obtained and demonstrated a calcification 3.5 cm below the carina with some suggestion of mediastinal widening, which was not commented on in the report (figure 1). given the non-reassuring fetal status and lack of improvement with intrauterine resuscitation with intravenous fluids and positioning, the decision was made to proceed with caesarean delivery under spinal anaesthetic as the patient was asymptomatic and hemodynamically stable. the patient underwent an uncomplicated primary caesarean section using spinal anaesthetic, delivering a viable female infant with apgar scores of 8 and 9 at 1 min and 5 min, respectively. after completion of the case, the patient's covid-19 swab had returned negative. repeat covid-19 swab was performed given the high false-negative rate. the patient's laboratory results were otherwise significant for a troponin of 0.056 ng/ml and a d-dimer of 2301 ng/ml. given the patient's history of a syncopal episode with an elevated d-dimer and troponin level, there was concern for a pulmonary embolism with right heart strain as the aetiology for her presentation. subsequently, a ct angiogram of the chest was obtained and demonstrated moderate pericardial effusion and an ascending thoracic aortic aneurysm measuring 4.5 cm in anteroposterior (ap) diameter without dissection; no pulmonary embolus was present (figures 2 and 3). the cardiology team was paged and performed a transthoracic echocardiogram (tte) at bedside with findings of a large pericardial effusion and apparent clotted blood within the pericardial space, as well as an ascending aortic root aneurysm measuring 5.2 cm without obvious dissection (figures 4 and 5). the team then discovered that the patient's father had died at age 40 from an acute aortic event. due to concern for a concealed dissection and possible need for surgical intervention, the patient was urgently transferred to a cardiothoracic surgery team at a quaternary centre. there she underwent urgent valve-sparing aortic root replacement. intraoperatively, the surgical team found significant hemopericardium with clotted blood, as noted on the tte, with a ~1 cm contained ascending thoracic aortic rupture tamponaded by the pulmonary artery in the setting of a bicuspid aortic valve and ascending aortic aneurysm. the patient's post-operative course was uncomplicated from both an obstetric and cardiothoracic standpoint and she was discharged home on postoperative day 5. as an outpatient, she subsequently underwent genetic testing and was diagnosed with loeys-dietz syndrome secondary to an smad3 mutation. aortic dissection or rupture is a rare occurrence in pregnancy and postpartum. aortic dissection during pregnancy makes up only 29 cases out of 9707 total cases documented by the international registry of acute aortic dissections over the past 20 years. 8 aortic dissection or rupture occurred in 36 out of 6.6 million pregnancies in a study by kamel et al. 9 despite the rare occurrence of this disease, pregnancy itself is a risk factor for aortic pathology. in women under 40 years old, up to 50% of aortic dissections occur during pregnancy or postpartum. 3 the incidence of aortic dissection or rupture is 5.5 per million patients during pregnancy and postpartum, as compared with 1.7 per million among non-pregnant patients. 9 in patients with aortic dissection during pregnancy, up to 62% are diagnosed with an underlying predisposing pathology. 8 the most commonly inherited and congenital conditions include marfan syndrome, bicuspid aortic valve and loeys-dietz syndrome. 8 obtaining an accurate family history can be essential in eliciting a patient's risk for this condition during pregnancy. our patient noted history of sudden death in her father around age 40 from an aortic dissection or rupture and was subsequently diagnosed with loeys-dietz syndrome. loeys-dietz syndrome is an autosomal dominant connective-tissue disorder due to genetic mutations, such as in the smad3 gene, as in our patient. 10 it confers higher risk to patients during pregnancy, including an increased risk of aortic dissection in the third trimester. 10 a thorough family history not only aids in making this rare diagnosis, but is also essential for preconception counselling in these patients. diagnosis of aortic dissection and rupture requires reliance on history, clinical examination and imaging. while the classic presentation of aortic dissection includes sharp chest pain radiating to the back and dyspnoea, syncope can be present in up to 13% of cases. 11 in case reports of aortic dissection in pregnancy, symptoms have included tearing chest pain, back pain, dyspnoea, hypertension, nausea/vomiting, syncope and seizure. [12] [13] [14] [15] the broad overlap between these symptoms and other more common complaints of pregnancy such as labour, pre-eclampsia and peripartum cardiomyopathy may confuse the clinician in diagnosing an aortic dissection. the gold standard for diagnosing aortic aneurysm and dissection is the ct angiogram. 16 if aortic disease is suspected antepartum, mri can also be used, but the use is limited to hemodynamically stable patients. 17 studies have additionally shown the utility of the echocardiogram as a tool for diagnosis given its high sensitivity and specificity. 16 transesophageal echocardiogram has a higher sensitivity and specificity for diagnosing aortic dissection than tte, but is an invasive procedure and less available in some places. 17 tte is a cost-efficient diagnostic modality that may aid in diagnosing hemopericardium, increasing diagnostic concern for aortic dissection or rupture, and allow for assessment of the aortic root size and the presence of bicuspid aortic valve. 17 the tte findings seen in this case, along with the patient's history of syncope, were the predominant clinical clues for the cardiology team to determine the diagnosis of aortic aneurysm rupture. at the time of our patient's presentation, the covid-19 pandemic both further complicated and aided in her diagnosis. up to 37% of pregnant patients with covid-19 have presented with dyspnoea. 18 during the work-up of the patient's syncope and dyspnoea, a d-dimer test was sent, a laboratory test that is frequently excluded from a dyspnoea work-up in pregnant patients given baseline elevations in d-dimer levels for healthy pregnant women. 19 during the covid-19 pandemic, however, d-dimer elevation has been associated with severe pneumonia in pregnancy and is included in the standard covid-19 panel at our hospital. 18 the elevated d-dimer and negative covid-19 testing in our patient spurred further work-up for pulmonary embolism, despite her improved symptoms, and ultimately led to her diagnosis. aortic dissection and rupture are rare occurrences in pregnant patients, and require a high index of clinical suspicion given the similarity of symptoms with other pathologies during pregnancy, particularly during the covid-19 pandemic. this case presents a rare pathology in a 33-year-old pregnant woman, in which covid-19 testing and echocardiography served to clinch the diagnosis and facilitate transfer for urgent surgical intervention. ► while the gold standard for diagnosing aortic aneurysm and dissection is ct angiogram, echocardiogram has the potential to quickly aid in diagnosis given its high sensitivity and specificity. ► maintaining a broad differential is essential to patient care during the covid-19 pandemic, as unrelated diagnoses with similar presentations to covid-19 may still affect patients. ► in pregnancy, a patient presenting with aortic dissection may have similar symptoms to more common complaints such as labour, pre-eclampsia and peripartum cardiomyopathy. ► more than half of pregnant patients with aortic dissection in pregnancy have an underlying predisposing pathology; eliciting a thorough family history is essential to care of these women. outcomes in pregnant women with acute aortic dissections: a review of the literature from 2003 to 2013 cardiac nursing pathophysiology, diagnosis, and management of aortic dissection aortic dissection in pregnancy: analysis of risk factors and outcome acute aortic dissection and pregnancy: review and meta-analysis of incidence, presentation, and pathologic substrates acute ascending aortic dissection during pregnancy glenn's thoracic and cardiovascular surgery aortic dissection related to pregnancy: the international registry of acute aortic dissection (irad) pregnancy and the risk of aortic dissection or rupture: a cohort-crossover analysis pregnancy with loeys-dietz: care informed by case series comparison of aortic dissection in patients with and without marfan's syndrome (results from the international registry of aortic dissection) dissecting aortic aneurysm during pregnancy dissecting aneurysm of the ascending aorta during the third trimester of pregnancy with cardiac tamponade aortic dissection in pregnancy acute aortic dissection in third trimester pregnancy without risk factors feasibility and accuracy of bedside transthoracic echocardiography in diagnosis of acute proximal aortic dissection guidelines for the diagnosis and management of patients with thoracic aortic disease: a report of the american college of cardiology foundation/ american heart association task force on practice guidelines, american association for thoracic surgery, american college of radiology, american stroke association, society of cardiovascular anesthesiologists, society for cardiovascular angiography and interventions, society of interventional radiology, society of thoracic surgeons, and society for vascular medicine clinical course of coronavirus disease-2019 in pregnancy large d-dimer fluctuation in normal pregnancy: a longitudinal cohort study of 4,117 samples from 714 healthy danish women we thank drs thomas marino and gaetano bello for their instrumental role in the patient's care and clinical decisions. contributors kb and kc contributed equally as first author to the paper. kb, kc and mc all participated in the patient's care. all authors contributed to the writing of the manuscript and approved the final manuscript.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. kelly bogaert http:// orcid. org/ 0000-0002-7376-7558 key: cord-285579-gvgt55o4 authors: asif, rehan; o' mahony, marcella sinead title: rare complication of covid-19 presenting as isolated headache date: 2020-10-29 journal: bmj case rep doi: 10.1136/bcr-2020-239275 sha: doc_id: 285579 cord_uid: gvgt55o4 an 18-year-old man presented with persistent isolated headache 2 weeks after recovering from acute covid-19 illness. extensive cerebral venous sinus thrombosis (cvst) was detected on ct venogram despite him having no other thrombotic risk factors. cvst can complicate covid-19. a high index of clinical suspicion is warranted as it can often have a subtle presentation with paucity of neurological symptoms. cerebral venous sinus thrombosis (cvst) accounts for 0.5% of strokes and has a wide spectrum of clinical presentation 1 ; however, headache is the most common manifestation occurring up to 90%, and sometimes it can be the only symptom. the majority of cases have a predisposing thrombotic risk factor. 1 2 covid-19 is caused by sars-cov-2 and typically presents as acute febrile illness with respiratory involvement as the most common presentation. 2 the complete clinical spectrum remains to unfold, but the association between thromboembolic events and covid-19 is increasingly recognised. we report a case of a young man developing cvst as a sequela of covid-19. a young man with no comorbidities developed acute covid-19 illness in the beginning of june 2020 with fever, cough and myalgia. he had confirmed positive throat swab pcr test in the community. the acute illness settled within a week at home, precluding hospital admission. a week later, he presented to the medical assessment unit with worsening headache. his headache was deemed to be a residual symptom of his recovery from initial covid-19 illness. he had a negative covid-19 swab test during that admission and was discharged after a period of observation. however, his headache persisted on discharge, and he re-presented to medical admissions with worsening headache for 2 weeks. his headache was global, severe in intensity and persistent with associated mild photophobia, but there was no fever, rash, visual symptoms, neck stiffness or any other neurological symptoms. he had no thrombotic risk factors and no family history of thromboembolism. on examination, he was alert and afebrile with glasgow coma scale of 15/15. his saturations were 100% on air, respiratory rate was 20/min, blood pressure was 130/70 mm hg and heart rate was 90/ min. there were no signs of meningeal irritation or any neurological deficit. rest of the examination was within normal limits. initial investigations showed normal cell counts with normal platelets. his coagulation profile, including prothrombin time, activated partial thromboplastin time and fibrinogen, was normal. c reactive protein was 30 mg/l. an initial plain ct of the brain did not show any focal parenchymal abnormality but showed hyperdense internal cerebral veins, raising the possibility of venous sinus thrombosis (figure 1). a subsequent ct venogram showed filling defects throughout the sigmoid and transverse sinuses bilaterally, extending into straight and superior sagittal sinuses (figure 2). there was no intracerebral haemorrhage. his headache was managed with simple analgesia. following discussion with the haematology and neurology teams, he was commenced on therapeutic dose of low-molecular-weight heparin and was monitored over 24 hours. he was discharged with the plan of continuing therapeutic dose of enoxaparin for 3 months and follow-up with the neurology team. the patient was followed up via telephonic consultation after 2 weeks, and he reported significant improvement in his symptoms and almost complete resolution of headache. while the clinical knowledge about covid-19 is still evolving, there is growing evidence that covid-19 predisposes to thromboembolic events and a hypercoagulable state. a multicentre dutch study comprising 184 patients with covid-19 pneumonia reported up to 49% cumulative incidence of thrombotic complications despite all patients receiving at least prophylactic anticoagulation. 3 an italian study of 388 patients reported a 21% cumulative incidence of thrombotic events. 4 however, the majority of studies showed a higher frequency of thrombotic events in patients with severe disease requiring intensive care unit (icu) admissions compared with those on general wards. 5 severe disease and icu admission seem to aggravate the pre-existing risk. cytokine-driven inflammatory immune response with subsequent endothelial damage could explain the increased risk. hypoxia is another factor driving pulmonary thrombosis in ventilated patients in icu. covid-19 has a neurotropic potential, and complications including acute cerebrovascular events, encephalitis and guillain-barré syndrome have been reported. 6 however, these are rare events, with cvst being an extremely rare complication of covid-19. it has been previously reported, but those cases had severe disease with significant neurological deficit at presentation, contrary to our case. cavalcanti et al reported three cases, all of whom have developed significant covid-19 pneumonia and severe neurological deficit. all three died of covid-19 complications. 7 hughes et al reported a case presenting with aphasia and hemiparesis with recent covid-19 infection. he also had other comorbidities including diabetes and hypertension. 8 our reported case is unique as he recovered from the initial covid-19 illness which was mild and did not even require hospital admission. headache was the only persisting symptom leading to his admission after he recovered from initial respiratory illness. he did not have other risk factors for venous thromboembolism. the extensive cvst in this case suggests that perhaps there are other unexplained factors that contribute to thrombosis in covid-19, and it is likely that the infection itself is an independent risk factor. further studies are required to explain the exact pathophysiology behind thromboembolic events in covid-19 cvst can be challenging to diagnose because headache rather than focal neurological deficit is the prominent feature. headache can also be part of acute covid-19 illness, which can further complicate the clinical picture. given the thrombotic risk with covid-19, a persistent worsening headache should be fully investigated especially in the presence of other thrombotic risk factors. this case highlights the need for continued vigilance to look out for this complication in covid-19. a missed diagnosis of cvst could potentially result in fatal consequences including raised intracranial pressure and intracerebral haemorrhage. we suggest that it should be considered in the differential diagnosis in patients presenting with worsening headache after acute or recent covid-19 infection. ► current evidence suggests a clear link between covid-19 and thromboembolic events. ► cerebral venous sinus thrombosis (cvst) can present with a wide range of clinical manifestations; however, headache can be the only presenting symptom. ► clinicians should have a high index of suspicion for cvst in covid-19, even in patients with mild illness. evaluation and management of cerebral venous thrombosis thrombosis of the cerebral veins and sinuses thrombosis risk associated with covid-19 infection. a scoping review incidence of thrombotic complications in critically ill icu patients with covid-19 venous and arterial thromboembolic complications in covid-19 patients admitted to an academic hospital in neurological and neuropsychiatric complications of covid-19 in 153 patients: a uk-wide surveillance study cerebral venous thrombosis associated with covid-19 cerebral venous sinus thrombosis as a presentation of covid-19 contributors ra was involved in the planning, literature search design and writing of the case report. msom was the consultant in change of this patient and provided oversight of the article, proof reading and review of the article. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-257884-5exwwxin authors: kumar, rajesh; kumar, jathinder; daly, caroline; edroos, sadat ali title: acute pericarditis as a primary presentation of covid-19 date: 2020-08-18 journal: bmj case rep doi: 10.1136/bcr-2020-237617 sha: doc_id: 257884 cord_uid: 5exwwxin the covid-19 pandemic is a highly contagious viral illness which conventionally manifests primarily with respiratory symptoms. we report a case whose first manifestation of covid-19 was pericarditis, in the absence of respiratory symptoms, without any serious complications. cardiac involvement in various forms is possible in covid-19. we present a case where pericarditis, in the absence of the classic covid-19 signs or symptoms, is the only evident manifestation of the disease. this case highlights an atypical presentation of covid-19 and the need for a high index of suspicion to allow early diagnosis and limit spread by isolation. the global covid-19 pandemic is caused by severe acute respiratory syndrome coronavirus 2, an enveloped single-stranded rna virus of zoonotic origin. transmission is mainly by aerosolised droplet contact, although surface fomite contact and faecal transmission are reported. symptoms of coronavirus include high-grade fever, severe cough and breathlessness. cytokine induction causes heavy neutrophilia in the alveoli, with capillaritis, fibrin deposition and thick mucositis causing respiratory failure, acute lung injury and death. conversely approximately one in eight patients are estimated to have an entirely benign course, transmitting the virus with no clinical manifestation of the disease. 1 2 chest pain in covid-19 may have cardiac causes, including acute coronary syndrome, pericarditis and myocarditis. 3 we present the first described case of acute pericarditis in the absence of initial respiratory symptoms secondary to covid-19. a 66-year-old farmer was admitted with 1-day history of acute-onset severe pleuritic chest pain, with four episodes lasting 10-15 min. the pain was worse when lying flat and relieved by leaning forward. he had no sweating nor fever. his history includes crohn's disease, hypertension and benign prostatic hyperplasia. his medications were esomeprazole, ramipril and tamsulosin. he had a 40 pack-year smoking history and a significant familial premature coronary disease. his vaccination schedule was up to date, and he had not travelled recently. on examination his temperature was 36.9°c, blood pressure was 134/83 mm hg, heart rate was 86 beats/min, respiratory rate was 16 breaths/min and an o 2 saturation of 99% on ambient air. his general, cardiovascular and respiratory examinations were normal. full blood count, urea and electrolytes, coagulation profile, and liver function tests were normal. his c reactive protein (crp) was 7 mg/l (normal <5 mg/l). high sensitivity cardiac troponin t (hs-ctnt) on admission and at 6 hours were 10 ng/l and 13 ng/l, respectively (normal <14 ng/l). his ecg showed st segment elevation in most leads with pr interval depression, and his chest x-ray (cxr) confirmed clear lungs with no abnormality (figure 1). transthoracic echocardiogram (tte) confirmed normal structure and function, although his pericardium was echo bright with no pericardial effusion (figure 2). ct of the thorax, abdomen and pelvis was normal. serum, nasopharyngeal and oropharyngeal swab specimen samples were sent for aetiological viruses associated with pericarditis. however, the patient presented in february 2020, which was early in the chronology of covid-19 in ireland and he did not have routine covid-19 screening swabs. complement levels, erythrocyte sedimentation rate and connective tissue screens were negative. nucleic acid amplification tests for influenza a and b were negative. cardiac mri (cmri) with adenosine stress perfusion showed a structurally normal heart with no effusion, fibrosis, infarction or infiltration. no inducible perfusion defects were evident during adenosine stress. his pericardium appeared mildly thickened (figure 3). differential diagnoses included myocarditis, acute coronary syndrome, pericarditis or pleuritis. a diagnosis of pericarditis was made based on typical chest pain, ecg presentation and tte. he admission ecg and chest x-ray on day 1. there is minimal st segment elevation in most leads with pr interval depression. was started on oral colchicine two times per day for 2 weeks and was discharged on day 4. the patient was readmitted on day 6 with recurrence of intermittent pleuritic chest pain and dry cough. vital signs, physical examination and blood tests were normal. cxr and ecg remained unchanged. viral serology was negative for routine viruses associated with pericarditis. a covid-19 viral pcr nasopharyngeal swab was positive. the public health team was notified and the patient was isolated. on day 8 he developed upper respiratory tract symptoms with peak temperature of 38.7°c. lymphopaenia (0.3×10 9 , normal >1×10 9 /l) with normal interleukin-6 (5.77, normal 0.09-7.26 pg/ml), crp and hs-ctnt were seen. blood culture showed no growth, and serial cxr remained normal. he recovered with symptomatic treatment and oral colchicines and was discharged on day 12. covid-19 has numerous adverse effects on the cardiovascular system. cardiac injury with troponin leak is associated with increased mortality in covid-19, and its clinical and radiographic features are difficult to distinguish from those of heart failure. [4] [5] [6] one reported covid-19 case with upper respiratory tract symptoms had haemorrhagic pericardial effusion with tamponade. 7 to our knowledge this is the first case where covid-19 presents as pericarditis, in the absence of evident respiratory or myocardial involvement. acute pericarditis is the most common disease of the pericardium and is responsible for 0.2% of chest pain-related hospitalisations. conversely 40%-85% of pericarditis cases are of unknown aetiology, probably due to difficulty in obtaining diagnostic pericardial samples. it is commonly seen in viral infections, including coxsackie, enterovirus, herpes simplex, cytomegalovirus, h 1 n 1 , respiratory syncytial virus, parvovirus b19, influenza, varicella, hiv, rubella, echovirus, and hepatitis b and c, although the viruses responsible in a given patient may be different genotypes of the same virus or different coexistent viruses. 8 9 in this patient respiratory swabs were initially negative, and viraemia first manifested with dry pericarditic symptoms, with a later diagnosis of covid-19. defining the underlying causative virus is not always possible. serological tests are only suggestive of a diagnosis of pericarditis and may yield false negative results. pericardial inflammation may prompt symptoms, yet may precede the generation of an observable pericardial effusion. tte is recommended to exclude significant effusion, although the absence of fluid does not rule out active pericarditis. cmri can describe pericardial thickening or small effusions, which are not appreciated on tte, assess for myocarditis on t2-weighted imaging, define pericardial inflammation on late gadolinium phase and quantify systolic function. 10 pericardiocentesis is the gold standard for definition of the underlying cause, providing a sufficient depth of fluid at a favourable angle is seen on tte, although this carries associated risk of serious cardiac injury and i woke up one day and i had a nagging pain in the center of my chest, which i never had or felt before, sharp like a knife and pressure on top of it as well. it was a constant nagging pain. it was relieving when i was sitting forward and back worsened as i was lying down in the bed. i felt more weak that day and had no energy. then pain got a bit worse at midday and my wife advised me to visit my doctor -general practitioner as a felt weak. after my doctor saw me, he advised me to go to the hospital and get myself check out to make sure i am not having a heart attack. i and my wife got very nervous. we came urgent to hospital emergency where a nurse examined me first, followed by a doctor and suggested they don't think that i am having a heart attack. he referred me to heart expert, who suggested that i have to be admitted in the hospital for more tests. they kept me for three days and all my tests like chest and body scans and bloods suggested that i have inflammation around the layers of heart. i was given some medication and discharged home that it will get better in a few days. i went home, the pain was there, it didn't went completely but improved slightly. it was worse with lying down in the bed. it wasn't going away despite me doing all what i was told for next few days. i came back to emergency department in 1st march as the pain wasn't settling at all with the medication. i went through all this process again. i was isolated, swabbed my nose for this new virus-covid-19. i did not had any sick contact or any other viral contact. i was nervous, and the result came positive. i was kept in separate part of hospital with no direct visitors to me and my family called me on the phone. i thought i am going to die but all the doctors and nurses reassured me. i developed slight cough and flu like illness for 2 days and then i got better next few days and i came home. i was told to follow strict isolation and precautions. no issues since discharge feeling very well. it's an unpleasant experience to be part of virus and i thought i won't make it as there was uncertainty about future events. i am greatly thankful to all the team who were involved in my care. a clinical diagnosis may be made if other supportive features are present. acute pericarditis is usually self-limiting, although it recurs in up to 30% of cases. most patients recover in 2-4 weeks with supportive measures, which would conventionally include nonsteroidal anti-inflammatory drugs (nsaids), colchicines and treating the causative disease. applying this to a patient with covid-19 requires balancing this conventional approach with an emerging understanding of pharmacotherapy in covid-19. colchicine inhibits microtubule, cell adhesion molecule and inflammasome activity, and is of use in preventing relapse in pericarditis at first presentation. 11 it is being trialled as a potential therapeutic anticytokine agent in covid-19 in italy, with one report of its use being associated with improvement. 12 conversely the use of nsaids in covid-19 may be harmful, with previously recognised increased risks of stroke and myocardial infarction (mi) with nsaids in acute respiratory infections raising concerns. no effective respiratory benefit has been seen with glucocorticoid use in covid-19, although their use in pericarditis may promote relapse. 13 14 currently, our understanding of the transmission dynamics and the spectrum of clinical illness of covid-19 is limited. cardiac involvement with various ecg presentations is possible and clinicians all across the globe need to be aware of this possibility. this case highlights the importance of recognising covid-19 infection with atypical clinical presentations such as pericarditis and non-specific ecg changes, and coordination with healthcare team regarding prompt isolation to decrease the risk of transmission of the virus and if any need of early hospitalisation. this case report is helpful in treating patients with this unique clinical presentation. twitter rajesh kumar @rajeshk33838720 and sadat ali edroos @saedroos contributors rk: treated and consented the patient, wrote the main manuscript, collected images and figures. jk: coauthored the manuscript, collected data on investigations. cd: coauthored the manuscript. sae: coauthored the manuscript. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. clinical features of patients infected with 2019 novel coronavirus in wuhan, china clinical characteristics of 3062 covid-19 patients: a metaanalysis coronavirus fulminant myocarditis saved with glucocorticoid and human immunoglobulin initial covid-19 affecting cardiac patients in china cardiac involvement in a patient with coronavirus disease 2019 (covid-19) association of cardiac injury with mortality in hospitalized patients with covid-19 in wuhan, china cardiac tamponade secondary to covid-19 viral communities associated with human pericardial fluids in idiopathic pericarditis clinical profile and influences on outcomes in patients hospitalized for acute pericarditis acute viral pericarditis without typical electrocardiographic changes assessed by cardiac magnetic resonance imaging colchicine in pericarditis covid-19 in kidney transplant recipients the anti-viral facet of anti-rheumatic drugs: lessons from covid-19 the use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (covid-19): the perspectives of clinical immunologists from china provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. rajesh kumar http:// orcid. org/ 0000-0002-8002-1551 sadat ali edroos http:// orcid. org/ 0000-0002-3267-6350 key: cord-281733-bsq0ewac authors: veyseh, maedeh; pophali, prateek; jayarangaiah, apoorva; kumar, abhishek title: left gonadal vein thrombosis in a patient with covid-19-associated coagulopathy date: 2020-09-07 journal: bmj case rep doi: 10.1136/bcr-2020-236786 sha: doc_id: 281733 cord_uid: bsq0ewac covid-19 disease is a viral illness that predominantly causes pneumonia and severe acute respiratory distress syndrome. the endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism. the exact mechanism of hypercoagulability is still under investigation, but it is known to be associated with poor prognosis. the most common thrombotic complication reported among these patients is pulmonary embolism. to our knowledge, gonadal vein thrombosis is an uncommon phenomenon that has not been reported in the setting of covid-19-associated coagulopathy. we report an unusual case of ovarian vein thrombosis and pulmonary embolism associated with covid-19 presenting with abdominal pain. to our knowledge, this is the first reported case of covid-19 with absent respiratory symptoms and presentation with venous thrombosis in an unusual location. summary covid-19 disease is a viral illness that predominantly causes pneumonia and severe acute respiratory distress syndrome. the endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism. the exact mechanism of hypercoagulability is still under investigation, but it is known to be associated with poor prognosis. the most common thrombotic complication reported among these patients is pulmonary embolism. to our knowledge, gonadal vein thrombosis is an uncommon phenomenon that has not been reported in the setting of covid-19-associated coagulopathy. we report an unusual case of ovarian vein thrombosis and pulmonary embolism associated with covid-19 presenting with abdominal pain. to our knowledge, this is the first reported case of covid-19 with absent respiratory symptoms and presentation with venous thrombosis in an unusual location. since the emergence of sars-cov-2 in december 2019, the world has faced an unprecedented public health crisis due to its high rate of transmission and the broad spectrum of the disease severity. the manifestation of the disease ranges from asymptomatic carriers to severe acute respiratory distress syndrome requiring mechanical ventilation and intensive care unit (icu) admission. the severe cases are more prone to arterial and venous thrombosis. these thrombotic events have been related to poor prognosis and linked to unexpected cardiac deaths. 1 the pathophysiology of thrombosis in covid-19 is hypothesised to be due to a hypercoagulable state from excessive inflammation, hypoxia, immobilisation and in severe cases of disseminated intravascular coagulation. 2 the most common location of thrombosis is pulmonary arteries. other reported venous thromboembolisms (vtes) include lower extremity thrombosis and catheter-associated thrombi. 3 ovarian vein thrombosis (ovt) is a rare and potentially fatal condition of postpartum period, which can act as a source of pulmonary embolism. 4 5 gonadal vein thrombosis has never been reported during this pandemic as a result of covid-19. we present a unique case which demonstrates left gonadal vein thrombosis secondary to covid-19 as the first presenting sign. a 52-year-old postmenopausal woman, with no known medical history, presented to our hospital with sudden onset of severe sharp right upper quadrant abdominal pain for 2 days. she described the pain to be unrelated to food and not associated with any other gastrointestinal (gi)-related symptoms. she denied recent fevers, cough or upper respiratory tract infection symptoms. she was afebrile (temp 97.7°f), pulse rate 93 beats/min, respiratory rate 22/min and oxygen saturation was 94% on room air, body mass index 29 kg/m 2 . her physical examination on admission was notable for shallow breathing, clear lungs and non-tender abdomen. the labs were significant for increased inflammatory markers, including ferritin (883 µg/l), c reactive protein (217 mg/l) and d-dimer was markedly elevated to 3813 ng/ml (table 1) . chest x-ray showed patchy peripheral densities seen in the upper lobe on the frontal view. on the lateral view there were patchy infiltrates posteriorly in the lower lobes suggestive of covid-19. ct of the abdomen/pelvis with contrast showed left ovt, which extended partially to the renal vein (figures 1 and 2). additionally, there was a finding of pulmonary embolism in the posterior branch of pulmonary artery in the right lower lobe (rll). pulmonary windows of the ct confirmed presence of bilateral lower lobe consolidations, ground-glass opacities in the right middle lobe and foci of consolidation in the lingula suggestive of covid-19 pneumonia. subsequent chest ct angiography confirmed the presence of an acute rll pulmonary artery thrombosis (figure 3). deep vein thrombosis (dvt) studies were negative for lower extremity venous clots. nasopharyngeal swab confirmed the diagnosis of covid-19. echocardiography showed normal biventricular systolic function in the absence of right heart strain. to further investigate secondary causes of hypercoagulability, rheumatologic panel including antinuclear antibody-extractable nuclear antigen panel, lupus anticoagulant, protein c, protein s and antithrombin iii were tested and resulted negative. tumour markers, including carcinoembryonic antigen, carbohydrate antigen 9/19 and cancer antigen-125 were negative and the initial ct scan unusual presentation of more common disease/injury of chest/abdomen/pelvis was without any evidence of malignancy. covid-19 was deemed to be the provoking cause of the thrombosis. the patient was started on therapeutic low molecular weight heparin (enoxaparin) 1 mg/kg two times per day, which resulted in significant improvement of the abdominal pain few hours after the first dose. she remained afebrile, denied any cough or shortness of breath, and oxygen saturation remained stable on room air. she was discharged after 3 days of hospitalisation on apixaban 10 mg two times per day for a week, followed by 5 mg two times per day for 3 months. during follow-up after a month, the patient reported mild abdominal pain, but remained afebrile and without any respiratory symptoms. she denied any bleeding complication. a repeat ct of the abdomen and pelvis showed resolution of thrombosis. d-dimer at the follow-up visit was 234 ng/ml. the covid-19 pandemic caused by the sars-cov-2 has affected millions of people worldwide. while a majority of the people affected by the virus remain asymptomatic, most patients admitted to the hospital present with severe respiratory illness. the most extensive published case series from china and new york report that the majority of patients present with fever, cough, fatigue and gi symptoms. 6 7 nearly 20% of these patients present with severe coagulation abnormalities. but rarely, vte may be the initial presenting feature in patients with sars-cov-2 infection. 8 concomitant vte, a potential cause of unexplained deaths, has been frequently reported in covid-19 cases. 8 9 our patient was distinctive in terms of presentation as she lacked the common respiratory symptoms, rather acute venous thrombosis in an unusual location prompted the diagnosis of covid-19. virchow's triad defined as blood stasis, endothelial injury and a hypercoagulable state leads to the pathogenesis of thrombosis. 10 patients with covid-19 usually present with dehydration and prolonged bed rest, which are risk factors for blood stasis. 11 sars-cov-2 infects ace 2 receptors, which is present on multiple organs, including the endothelial cells. in a recent study on postmortem autopsies, there was evidence of endothelitis caused by either direct viral invasion of the endothelial cells or endothelial injury derived from the inflammatory response. this possibly explains why patients with endothelial dysfunction due to pre-existing conditions are more prone to organ failure secondary to microthrombi and present with a more severe form of the illness. 12 also, the covid-19 infection can cause a severe inflammatory response, which results in the release of cytokines such as interleukin 6, tumour necrosis factor-alpha. 13 these cytokines stimulate the activation of the coagulation cascade and increase the risk of vte. 14 other proposed pathophysiology behind an increased propensity to thrombosis is the finding of antiphospholipid antibodies, which can transiently arise in patients with critical illness and various infections and potentially contribute to a hypercoagulable state. 15 16 based on the available literature, most thrombotic events in covid-19, including pulmonary embolism or dvts, develop in critically ill patients with severe pulmonary disease. 2 17 18 our case was unique as she had no respiratory symptoms and an otherwise uncomplicated clinical course; however, she still presented with a thrombotic complication in an unusual site. ovt is a rare entity that is most commonly seen in the postpartum period. other causes of ovt include pelvic unusual presentation of more common disease/injury inflammatory disease, recent gynaecological or abdominal surgery, hypercoagulable state and underlying malignancy. 5 an underlying hypercoagulable state has been reported in 50% of the cases with ovt. 19 regardless of the aetiology, rightsided ovt accounts for 70%-90% of the cases. it can likely be related to dextrotorsion of the uterus that compresses the right ovarian vein, antegrade flow and relatively more incompetent valves of the right ovarian vein. 20 the most common symptoms are fever (80%) and right-sided pelvic pain (55%). 21 our patient was unusual as she did not have a fever on presentation, and the venous thrombosis was on the left side. this condition can be fatal due to the serious life-threatening complication from thrombus extension into the systemic veins and subsequent pulmonary artery embolisation. the incidence of ovt complicated by pulmonary embolism is reported to be approximately 25%. 22 our case was diagnosed with ovt and subsequent pulmonary embolism. it is unclear if the pulmonary embolus occurred secondary to embolisation of ovarian thrombosis or a primary thrombus as a result of hypercoagulability state due to covid-19, specifically in the absence of lower extremity dvt. the treatment for ovt is anticoagulation for 3-6 months. however, no clear guideline is available about the duration of therapy, and non-vitamin k antagonist oral anticoagulants have not yet been studied in such cases. 5 20 the only widely available treatment in covid-19-associated coagulopathy is prophylactic dose of low molecular weight heparin, which should be considered in all patients (including non-critically ill) who require hospital admission for covid-19 infection. 23 use of higher-intensity, non-standard anticoagulation currently lacks efficacious evidence in covid-19. 10 a study by klok et al 2 showed a 31% incidence of thrombotic complications in icu patients with covid-19 infection despite being on prophylactic anticoagulation. considering this remarkably high incidence of vte, it is suggested to increase the intensity of anticoagulation despite the lack of randomised evidence to support the practice. current evidence suggests d-dimer, an indicator of fibrin breakdown, can be used to assess severity of clot burden and guide initiation and monitoring of therapy. 1 24 in summary, we present an interesting case with an unusual presentation of covid-19 who presented with abdominal pain and no significant respiratory symptoms and was diagnosed with thrombosis of the left ovarian vein. our case emphasises the high risk of coagulopathy in covid-19 cases, even without a severe systemic infection. evaluation and risk stratification for thrombosis with coagulation markers and d-dimer should be incorporated in the management of covid19. 25 learning points ► this is the first case report of ovarian vein thrombosis secondary to covid-19-associated coagulopathy (cac). ► cac can present with thromboembolic complications even in the absence of typical respiratory symptoms. ► cac is associated with poor prognosis and prompts prophylactic anticoagulation in all patients who require hospitalisation. ► coagulopathy is independently indicative of severe illness even in the absence of lung involvement. prothrombin time/ partial thromboplastin time/international normalised ratio, fibrinogen and d-dimer should be monitored in all patients with covid-19 requiring hospitalisation. abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia incidence of thrombotic complications in critically ill icu patients with covid-19 confirmation of the high cumulative incidence of thrombotic complications in critically ill icu patients with covid-19: an updated analysis ovarian vein thrombosis: incidence of recurrent venous thromboembolism and survival ovarian vein thrombosis: a rare cause of abdominal pain outside the peripartum period clinical characteristics of covid-19 in new york city clinical characteristics of covid-19 in china. reply prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus statement before guidelines epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study covid-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: jacc state-of-the-art review venous thrombosis and arteriosclerosis obliterans of lower extremities in a very severe patient with 2019 novel coronavirus disease: a case report endothelial cell infection and endotheliitis in covid-19 dysregulation of immune response in patients with coronavirus 2019 (covid-19) in wuhan, china bidirectional relation between inflammation and coagulation lupus anticoagulant is frequent in patients with covid-19 infectious origin of the antiphospholipid syndrome prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia high risk of thrombosis in patients with severe sars-cov-2 infection: a multicenter prospective cohort study postpartum ovarian vein thrombosis postpartum ovarian vein thrombosis: an unpredictable event: two case reports and review of the literature acute appendicitislike symptoms as initial presentation of ovarian vein thrombosis ovarian vein thrombosis in the nonpregnant woman: an overlooked diagnosis isth interim guidance on recognition and management of coagulopathy in covid-19 clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study d-dimer is associated with severity of coronavirus disease 2019: a pooled analysis contributors supervised and reviewed by ak. patient was under the care of mv. report was written by mv, aj and pp.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-263530-t9ryky6f authors: kamal, yasmine mohamed; abdelmajid, yasmin; al madani, abubaker abdul rahman title: cerebrospinal fluid confirmed covid-19-associated encephalitis treated successfully date: 2020-09-16 journal: bmj case rep doi: 10.1136/bcr-2020-237378 sha: doc_id: 263530 cord_uid: t9ryky6f the covid-19 pandemic that attracted global attention in december 2019 is well known for its clinical picture that is consistent with respiratory symptoms. currently, the available medical literature describing the neurological complications of covid-19 is gradually emerging. we hereby describe a case of a 31-year-old covid-19-positive patient who was admitted on emergency basis. his clinical presentation was primarily neurological, rather than the covid-19’s classical respiratory manifestations. he presented with acute behavioural changes, severe confusion and drowsiness. the cerebrospinal fluid analysis was consistent with covid-19 encephalitis, as well as the brain imaging. this experience confirms that neurological manifestations might be expected in covid-19 infections, despite the absence of significant respiratory symptoms. whenever certain red flags are raised, physicians who are involved in the management of covid-19 should promptly consider the possibility of encephalitis. early recognition of covid-19 encephalitis and timely management may lead to a better outcome. the covid-19 pandemic that attracted global attention in december 2019 is well known for its clinical picture that is consistent with respiratory symptoms. currently, the available medical literature describing the neurological complications of covid-19 is gradually emerging. we hereby describe a case of a 31-yearold covid-19-positive patient who was admitted on emergency basis. his clinical presentation was primarily neurological, rather than the covid-19's classical respiratory manifestations. he presented with acute behavioural changes, severe confusion and drowsiness. the cerebrospinal fluid analysis was consistent with covid-19 encephalitis, as well as the brain imaging. this experience confirms that neurological manifestations might be expected in covid-19 infections, despite the absence of significant respiratory symptoms. whenever certain red flags are raised, physicians who are involved in the management of covid-19 should promptly consider the possibility of encephalitis. early recognition of covid-19 encephalitis and timely management may lead to a better outcome. the covid-19 virus, classified as sars-cov-2, emerged in wuhan, china, and was initially identified as the new coronavirus disease. the who eventually named it as covid-19 on 11 february 2020. later on 5 june 2020, the who officially announced that covid-19 has infected 6 535 354 individuals and claimed more than 387 155 lives worldwide. 1 covid-19 is not the first coronavirus to infect humans. other human coronaviruses (hcov) include six other members designated as sars-cov, middle east respiratory syndrome-cov, hcov-hku1, hcov-nl63, hcov-oc43 and hcov-229e. 2 as described in the literature, covid-19 possesses neuroinvasive potentials, which makes the central nervous system (cns) an important target. there are multiple proposed mechanisms of cns involvement, including retrograde movement from the olfactory nerve, entry into cns via circulating lymphocytes or entry via permeable bloodbrain barrier. 3 there are several neurological manifestations that have been described in patients with severe respiratory distress. 4 but this case is unique due to the fact that the patient's symptoms were mainly neurological in nature, that was preceded with a mild, self-limiting cough. what also enhances the uniqueness of this case is the presence of a very few reported cases of established encephalitis alongside an objective evidence of the virus itself in cns. 5 6 on 10 may 2020, a 31-year-old previously healthy man, who happened to live in a particular area with uncontrolled covid-19 spread in dubai, started experiencing some mild, self-limiting cough symptoms without any episode of fever. this was not brought to medical attention and resolved spontaneously within 2 days. on 12 may 2020, he started to become physically and verbally aggressive, as stated by his acquaintances. on 14 may 2020, he presented to the emergency department in rashid hospital with an altered mental state and abnormal behaviour. the patient's acquaintances clearly stated that the patient does not suffer from unusual presentation of more common disease/injury any comorbidities and denied any history of alcohol intake or substance abuse. the patient was afebrile. his heart rate was 76/min, blood pressure was 120/80 mm hg, respiratory rate was 12/min and oxygen saturation on room air was 100%. neurological examination revealed acute confusion state associated with severe agitation and fluctuations in the level of consciousness. cranial nerves examination was unremarkable. the motor examination including tone, power in upper and lower limbs, and deep tendon reflexes was normal as well. coordination was difficult to assess at this point. no neck stiffness or other meningeal signs were evident. chest examination, including inspection, auscultation, percussion and palpation, revealed no abnormalities. abdominal examination revealed a soft abdomen and present bowel sounds, without any evidence of tenderness or organomegaly. ► brain ct without contrast revealed multiple hypodensities in the external capsules bilaterally, the insular cortex and the deep periventricular white matter of the frontal lobes bilaterally (figure 1). another brain ct was performed 48 hours after the initial one, but did not reveal any significant interval changes (figure 2). ► chest x-ray was unremarkable. ► pulmonary ct showed normal attenuation in both lungs without any appreciable air space consolidations, pneumothorax or pleural effusion. no evidence of ground glass opacities. ► pulmonary ct angiogram shows good flow of contrast of the main pulmonary trunk, right and left main pulmonary arteries, as well as the lobar, segmental and subsegmental branches without any appreciable filling defects. no evidence of pulmonary embolism. ► abdominal ct was normal ► brain mri with contrast, performed after 2 weeks to comply with our hospital's protocol that only allows covid-19-negative patient to get in contact with the mri machine, revealed abnormal signal intensity in the temporal lobe cortex bilaterally in a rather symmetrical fashion. in addition, the involvement of the parasagittal frontal lobes bilaterally was evident as well, displaying bright signals on t2-fluid attenuated inversion recovery and t2-weighted images with corresponding diffusion restriction. these findings are suggestive of encephalitis (figures [3] [4] [5] . electrophysiological studies ► electroencephalogram did not display any significant epileptic discharges. that could possibly be due to the masking effect of lorazepam that was given to the patient to manage his agitation. living in an area where there is a higher infection rate of covid-19 is a red flag by itself. given the presenting symptoms, covid-19 encephalitis should be considered, as well as acute metabolic disorders, such as renal and hepatic encephalopathies. our patient had an initially elevated bilirubin level; however, the alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase were within normal limits (table 1) . hepatitis c antibodies and hepatitis b surface antigen were negative, and abdominal ct scan was normal too. the elevated bilirubin normalised within 2 weeks, indicating that this elevation was non-specific. acute cerebrovascular accident or toxic insults should also be wisely ruled out. nevertheless, viral, bacterial, parasitic, mycobacterial and fungal encephalitis should be excluded. covid-19 encephalitis should be also considered in the differential diagnoses, particularly nowadays. such life-threatening conditions need proper screening for all the above mentioned to avoid uninvited complications. the patient was admitted in an isolated high dependency care unit. primary care was initiated, including nasogastric tube and foley's catheter insertion, oxygen supplementation by nasal cannula, as well as intravenous fluids for the purpose of hydration. the following treatment plan was decided on and was immediately started, and it included chloroquine 150 mg two times per day for 2 weeks, along with two tablets of lopinavir-ritonavir two times per day for 2 weeks. seven hundred and fifty milligrams of intravenous acyclovir sodium, three times per day, was started empirically before the cerebrospinal fluid (csf) results were obtained, addressing the possibility of herpes simplex virus (hsv) i and ii encephalitis. the decision to continue the acyclovir for a further duration of 2 weeks was made, despite of the absence of evidence of hsv in the csf, based on the fact that the patient was gradually improving, and there might be possibility of a false negative herpes simplex pcr csf test. levetiracetam 1 g two times per day was started empirically, tackling the suspicion of non-convulsive seizure as a possible cause for the altered level of consciousness. in addition, 2 mg of intravenous lorazepam and 2.5 mg of intramuscular haloperidol two times per day were given as required, whenever needed. enoxaparin 40 mg subcutaneously once a day and pantoprazole 40 mg daily were prescribed for deep venous thrombosis prophylaxis and gastrointestinal prophylaxis, respectively. for supplementation, 10 ml of calcium-magnesium-d 3 -zinc (osteocare) 150 mg-75 mg-75 unit-3 mg/5 ml syrup was given as well. after 1 week of his admission, the patient's level of consciousness improved dramatically, despite his fluctuating confusion and agitation. the same management plan was resumed, except an increment in the enoxaparin dose to 70 mg subcutaneously two times per day was made, as a result of the patient's elevated d-dimer levels of 2.6 mg/dl (table 2) . the patient eventually became fully conscious and well coherent, with a complete resolution of his psychosis and agitation. after 2 weeks, he was successfully able to resume his normal life routine. fifteen days after admission, covid-19 rna pcr test was performed again on samples from both the nasopharynx and the csf (table 3) . both results turned out to be negative. in addition, the bilirubin level improved as well. the patient was safely discharged from the hospital on 5 june 2020, retaining his normal baseline condition. on discharge, he was only prescribed vitamin c and zinc supplements. he did not require further anticoagulation as his d-dimer fell back to its normal limits and his pulmonary angiogram was unremarkable. a telephonic follow-up consultation was held with the patient, where he confirmed that he remains unquestionably in a good condition. sars-cov-2 is acknowledged to affect the nervous system and induce polyneuropathy, encephalitis and acute ischaemic strokes. 7 8 the mechanism by which coronavirus affects the cns is not yet fully understood. it is sensible to agree that the mechanism of neuroinvasion could be either the traditional viral entry into cns via circulating lymphocytes, or its entry via a permeable blood-brain barrier. 3 one would debate that the acuteness of our patient's neurological symptoms, as displayed in the symptomatology, brain imaging, as well as the elevated d-dimer, might suggest a viral influence on the vascular network of the cns. nevertheless, the possible mechanism of injury of the brain's vascular endothelium could be some disruption in the vascular structures, eventually leading to clotting and infarction. [9] [10] [11] this, however, was not suggested in the presented case. a detailed look at the mri of the brain (figures 3-5) study reveals an abnormal distribution that is symmetrical bilaterally, affecting mainly the frontal and temporal lobes. this picture highly suggests a viral pathology rather than a vascular insult. as explained earlier, the behavioural changes, acute psychosis, acute confusional state and drowsiness were the initial and main presenting symptoms in a patient with covid-19 without major respiratory symptoms, except for the self-limiting episode of mild cough that resolved spontaneously, prior to his presentation, without medical interference. the early suspicion of covid-19 encephalitis and performing the appropriate csf studies was the key to establishing the correct diagnosis and timely management. despite the absence of csf pleocytosis, the suspicion of cns encephalitis should still be considered. upadhyayula suggested that viral meningoencephalitis may occur frequently in the lack of csf pleocytosis. 12 in addition, erdem et al also suggested that the suspicion of cns infections should not be underestimated despite the lack of csf pleocytosis. 13 there are also several published case series that described patients without csf pleocytosis in relation to bacterial meningitis, herpes simplex encephalitis and enteroviral meningitis. [14] [15] [16] patients with meningoencephalitis associated with covid-19 may not present with the commonly known flu-like illness, as with the presented patient. 17 we conclude that early establishment of the diagnosis and the immediate commencement of a management plan may contribute to a better outcome. ► a red flag of the possibility of covid-19 encephalitis should be raised whenever patients present with abnormal behaviour, acute psychosis, confusion state or drowsiness. ► prompt and specific investigations to diagnose this condition should not be hindered in absence of the more common respiratory covid-19 symptoms such as anosmia, dysgeusia, flu-like symptoms, headache, and sensory or motor deficits. ► early diagnosis and management of such cases is important to avoid further undesired complications. who. coronavirus disease situation report epidemiology and clinical presentations of the four human coronaviruses 229e, hku1, nl63, and oc43 detected over 3 years using a novel multiplex real-time pcr method neuroinfection may contribute to pathophysiology and clinical manifestations of covid-19 steroid-responsive encephalitis in coronavirus disease 2019 a first case of meningitis/encephalitis associated with sars-coronavirus-2 encephalitis as a clinical manifestation of covid-19 neurological manifestations in severe acute respiratory syndrome large artery ischaemic stroke in severe acute respiratory syndrome (sars) coronavirus disease 19 (covid-19) and cardiovascular disease coagulopathy and antiphospholipid antibodies in patients with covid-19 ace2-ang-(1-7)-mas axis in brain: a potential target for prevention and treatment of ischemic stroke 1823. incidence of meningoencephalitis in the absence of csf pleocytosis central nervous system infections in the absence of cerebrospinal fluid pleocytosis cerebrospinal fluid white cell count: discriminatory or otherwise for enteroviral meningitis in infants and young children? analysis of clinical outcomes in pediatric bacterial meningitis focusing on patients without cerebrospinal fluid pleocytosis normocellular csf in herpes simplex encephalitis covid-19-associated meningoencephalitis complicated with intracranial hemorrhage: a case report we would like to thank dr raheel ahmed for his assistance in direct patient care, as well as dr maria khan, for the final review of the article. the contributors of this work include ymk for direct medical care and writing the structure of the article; ya for direct patient care, editing the article and the submission process; and aaaam for direct patient care, as well as being the most responsible physician. we would also like to express our gratitude for the infectious disease team, the psychiatry team and the nursing team in rashid hospital for helping us provide the complete medical care that the patient needs. last but not least, we are thankful to the patient for consenting to publish his case.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. yasmin abdelmajid http:// orcid. org/ 0000-0003-1920-7602 key: cord-341246-fz66z2p2 authors: bhattacharyya, pranab j; attri, pawan k; farooqui, waseem title: takotsubo cardiomyopathy in early term pregnancy: a rare cardiac complication of sars-cov-2 infection date: 2020-09-28 journal: bmj case rep doi: 10.1136/bcr-2020-239104 sha: doc_id: 341246 cord_uid: fz66z2p2 nan a 32-year-old primigravida at a 38-week gestation was initially admitted in cardiology isolation ward on referral by her local obstetrician for inferolateral st-segment elevation on ecg (figure 1a) which was obtained for complaints of new york heart association functional class ii symptoms with palpitations of a 3-day duration. except for a blood pressure of 150/100 mm hg on presentation, the rest of her physical examination, vital signs and medical history were insignificant. she was on amlodipine for gestational hypertension. a transthoracic echocardiogram (tte) demonstrated hypokinetic mid and akinetic apical left ventricular (lv) segments and hypercontractile basal segments with prominent apical ballooning typical of takotsubo cardiomyopathy (ttc) (figure 1b, arrows). two-dimensional speckle tracking echocardiography revealed lv global longitudinal strain (gls) of −13.9 and ejection fraction (ef%) of 38% ( figure 1c ). blood tests showed elevated troponin i (37.00 pg/ml, normal <26.20) and n-terminal pro b-type natriuretic peptide (nt-probnp) (1312.00 pg/ml, normal <115.00). nasopharyngeal swab reverse transcription pcr (rt-pcr) test was positive for sars-cov-2 infection. coronary angiography (cag) was deferred due to her active covid-19 status. she was further managed in the ward of our dedicated covid-19 hospital where she was started on medical therapy with bisoprolol and enoxaparin (40 mg subcutaneous two times per day for 5 days) along with oral vitamins and antibiotic as per local treatment protocol for patients with covid-19. regular maternal and fetal monitoring continued. as oxygen saturation in room air and respiratory rate were maintained within normal limits without any clinical evidence of pneumonia or respiratory failure, she did not require management in the intensive care unit for either non-invasive or invasive mechanical ventilation at any stage during her 7-day stay in the covid-19 ward. additional laboratory tests showed leucocytosis (20.48×10 9 /µl, normal 4.00-11.00), neutrophilia (85.8%, normal range 37-72), lymphopenia (9.2%, normal range 20-40), neutrophil-lymphocyte ratio (9, normal 1-3), raised levels of d-dimer (0.69 µg/ml, normal <0.05), lactate dehydrogenase (456 u/l, normal range 120-246), alkaline phosphatase (188 u/l, normal range 38-126) and globulin (3.5 g/dl, normal range 2.80-3.20), low levels of albumin (3.0 g/dl, normal range 3.50-5.00) and albumin/globulin ratio (0.90, normal 1.25-1.51) and normal levels of ferritin (116 ng/ml, normal range 11-306.8), total bilirubin (0.50 mg/dl, normal range 0.20-1.3), aspartate aminotransferase (37 u/l, normal 17-59) and alanine aminotransferase (28 u/l, normal range 4-50). on day 8, her rt-pcr test was negative and due to the onset of early labour, she was shifted to labour and delivery ward for necessary obstetrical management. subsequently on the same day, she underwent an uneventful caesarean section delivery under spinal anaesthesia for fetal distress and associated cephalopelvic disproportion. despite a diagnosis of ttc, an expedited delivery in our patient was not considered by the obstetrical unit as there was no evidence of clinical or haemodynamic worsening of maternal or fetal status. repeat tte on day 13 on transfer to the cardiology ward showed the normalisation of the lv regional wall motion abnormalities (rwma) and significant improvement of gls (−16.5) and ef% (51%) (figure 1d) further ratifying the diagnosis of ttc. subsequent cag on day 14 revealed non-obstructive coronary artery disease (cad) involving the left anterior descending artery ( figure 1e, arrows) . she was finally discharged from the cardiology ward after full recovery on day 16 with aspirin, atorvastatin and bisoprolol. as typified by this index case, ttc can mimic acute st-segment elevation myocardial infarction and is considered to be a reversible form of cardiomyopathy characterised by a complete recovery of rwma and lv function within weeks of presentation. incidental cad can be present in up to 10% cases. 1 although ttc classically affects postmenopausal women, it has been infrequently reported previously in pregnant women unrelated to sars-cov-2 infection. 2 this is the first reported case of ttc in pregnancy as a manifestation of sars-cov-2 infection during this ongoing pandemic. ttc can be preceded by emotional or physical stressful triggers. coronary artery vasospasm, coronary microvascular dysfunction, lv outflow tract obstruction and catecholamine surge have all been elucidated as potential mechanisms. as ttc has also been reported with viral infections, the more intense inflammation associated with covid-19 may contribute to its development. deranged inflammatory markers were also a notable finding in our patient described previously. whether the inflammatory response of sars-cov-2 infection and any specific markers that may portend a greater likelihood of development of ttc especially in pregnancy may be a subject matter for further study. the overall prognosis of ttc is favourable, with full recovery of lv function seen in most patients by 2 months. 3 pregnant women may be at greater risk for sars-cov-2 infection as the virus enters the cell via the ace 2 receptor, which is upregulated in normal pregnancy. 4 therefore, treating physicians dealing with the covid-19positive pregnant population need to remain vigilant towards this rare cardiac complication of sars-cov-2 infection. contributors pjb, pka, and wf were involved in patient management. pjb prepared the manuscript. pjb and pka acquired the echocardiographic images and pjb and wf performed the coronary angiogram. all authors have revised the manuscript and approved of the final draft. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. chapter 40 st-segment elevation myocardial infarction takotsubo cardiomyopathy in pregnancy takotsubo syndrome in the setting of covid-19 sars-cov-2 infection and covid-19 during pregnancy: a multidisciplinary review competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. i express my gratitude to the entire team of doctors and healthcare workers for providing me best possible care leading to my complete recovery. ► the presentation of takotsubo cardiomyopathy can mimic stsegment elevation myocardial infarction but in the absence of angiographic evidence of significant obstructive coronary artery disease. ► typical echocardiographic finding is reversible left ventricular apical ballooning (resembling the 'takotsubo' or japanese 'octopus trap') with systolic dysfunction. ► this condition can be triggered by high emotional stress with a preponderance in postmenopausal women. ► for the first time during this ongoing pandemic, this entity has been documented to occur as a cardiac complication of sars-cov-2 infection in term pregnancy. ► appropriate conservative management leads to its complete recovery.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-259250-ybfyiykz authors: korem, sindhuja; gandhi, haresh; dayag, decerie baculi title: guillain-barré syndrome associated with covid-19 disease date: 2020-09-21 journal: bmj case rep doi: 10.1136/bcr-2020-237215 sha: doc_id: 259250 cord_uid: ybfyiykz clinical manifestations of covid-19 are known to be variable with growing evidence of nervous system involvement. in this case report, we describe the symptoms of a patient infected with sars-cov-2 whose clinical course was complicated with guillain-barré syndrome (gbs). we present a case of a 58-year-old woman who was initially diagnosed with covid-19 pneumonia due to symptoms of fever and cough. two weeks later, after the resolution of upper respiratory tract symptoms, she developed symmetric ascending quadriparesis and paresthesias. the diagnosis of gbs was made through cerebrospinal fluid analysis and she was successfully treated with intravenous immunoglobulin administration. clinical manifestations of covid-19 are known to be variable with growing evidence of nervous system involvement. in this case report, we describe the symptoms of a patient infected with sars-cov-2 whose clinical course was complicated with guillain-barré syndrome (gbs). we present a case of a 58-year-old woman who was initially diagnosed with covid-19 pneumonia due to symptoms of fever and cough. two weeks later, after the resolution of upper respiratory tract symptoms, she developed symmetric ascending quadriparesis and paresthesias. the diagnosis of gbs was made through cerebrospinal fluid analysis and she was successfully treated with intravenous immunoglobulin administration. at the time of writing, there exist more than 100 000 new cases, about five million confirmed cases, and over 350 000 deaths from covid-19 worldwide according to the who. the first series of patients were reported in wuhan, china, in december 2019 and were typically diagnosed in patients with a pneumonia-like presentation. 1 there is growing evidence that covid-19 can also affect the nervous system. to date, there are only 12 published cases of covid-19-related guillain-barré syndrome (gbs). 2 we have a limited understanding of how covid-19 leads to gbs as it needs to be further investigated. we report a case of gbs in a patient with covid-19 in new jersey. gbs is an acute, autoimmune, polyradiculoneuropathy characterised by progressive ascending weakness and diminished/absent reflexes. patients may or may not have additional symptoms involving cranial nerves, sensory symptoms and autonomic dysfunction. 2 the abnormal immune response may be triggered by viral/bacterial infections, immunisations or surgery. the diagnosis is made through clinical findings, cerebrospinal fluid analysis (csf) and nerve conduction studies. treatment involves the administration of intravenous immunoglobulins, plasma exchange, continuous monitoring and supportive care. though the syndrome is rare, early diagnosis and treatment can significantly improve outcomes and avoid the need for ventilatory support. 3 our patient was a 58-year-old woman with a medical history significant for cervical spondylosis and disc herniation for which she underwent an anterior cervical discectomy and anterior interbody arthrodesis at c4-c7 3 years ago. two weeks prior to this hospital admission, she developed a fever, cough and back pain amidst the covid-19 pandemic. the patient tested positive for covid-19 and was treated with azithromycin for 5 days at home. subsequently, over the next 2 weeks, her fever and cough resolved, but the lower back pain persisted. this was characterised by a throbbing, 7/10 intensity (numeric rating scale), radiating to both the lower extremities. she then had a new onset of numbness, pins and needles sensation in the left lower extremity associated with mild weakness. these same symptoms then progressed to the contralateral lower extremity over the next 24 hours with an unstable gait. this progression triggered an emergency room visit. she had no headaches, loss of consciousness, changes in mental status, changes in vision and speech, difficulty swallowing, seizurelike symptoms or urine/bowel incontinence. she denied any history of tick bites or trauma. physical examination findings included stable vital signs and motor strength was 5/5 (oxford scale) in all four extremities, normal deep tendon reflexes in both upper and lower extremities and a negative babinski sign bilaterally. there was no defined spine sensory level and no upper motor neuron weakness findings. she was admitted to the hospital for idiopathic paresthesias with suspicion of lumbosacral radiculopathy. on the day of admission, notable laboratory findings include a white cell count of 13.5×10 9 /l, normal erythrocyte sedimentation rate, c-reactive protein, vitamin b 12 level andthyroid stimulating hormone. a ct scan of the head and radiograph of the lumbar spine was performed. the ct scan of the head showed no intraparenchymal mass or lesions, no haemorrhage and no findings of normal pressure hydrocephalus. radiograph of the spine showed multilevel degenerative changes. mri of the lumbar spine without contrast (see figure 1 ) showed moderate bilateral and moderate left-sided neural foraminal narrowing at l2-l3 and l3-l4, respectively, and unremarkable conus medullaris. because of persistent headaches, an mri of the brain was done, which showed normal findings. over the next 24 hours, a repeat covid-19 test sent came back positive. the patient developed worsening weakness with muscle strength new disease 3/5 in both lower extremities and new onset of weakness of her left upper extremity with muscle strength 4/5. additional symptoms included numbness, tingling and paresthesias of the affected extremities. now there was a change in her examination with diminished deep tendon reflexes when compared with the previous day. with the patient exhibiting ascending weakness with diminished reflexes, an urgent lumbar puncture was performed to rule out gbs. initially, a lumbar puncture was deferred as there was a low suspicion for gbs based on the patient's presentation with normal deep tendon reflexes and an unremarkable conus medullaris. csf revealed findings suggestive of albumin-cytologic disassociation with a white cell count of 2 cu/mm and protein count of 117 mg/dl. nerve conduction study was not performed, as this was not available in the inpatient setting. on the day of hospital presentation, the initial suspicion was lumbar radiculopathy in the setting of back pain with paresthesias. as studies emerged showingpatients with covid-19 often present with hypercoagulable changes including stroke, imaging of the head was performed to rule out this pathology. other differentials on admission were transverse myelitis, but the patient did not have a clear sensory level and subsequently did not have inflammatory findings on csf analysis. later as the patient exhibited clinical findings of ascending paralysis with diminished deep tendon reflexes, the diagnosis of gbs became more evident. with the initial suspicion of traditional lumbar radiculopathy, physical therapy was initiated. as the diagnosis of gbs became clearer, the patient was given 2 mg/kg intravenous immunoglobulins for 4 days and the respiratory status was monitored by checking vital capacity every 4 hours. she also received gabapentin 300 mg two times per day for neuropathic pain. fortunately, our patient had stable vital capacity throughout the stay and no signs of respiratory muscle weakness. after receiving this treatment, the patient's symptoms improved significantly and she was discharged to an acute rehabilitation facility for regular physical therapy. follow-up was established with the patient who mentioned that her symptoms improved. she had complete resolution of paresthesias and about 80% improvement in motor strength of all extremities. currently, the patient is performing daily physical therapy successfully at her rehab facility. sars-cov-2 frequently afflicts the respiratory system and gastrointestinal tracts. it shares its identity with other human coronaviruses including sars-cov and middle east respiratory syndrome coronavirus. in this group of viruses, the respiratory system is commonly affected but they have also shown the involvement of the nervous system. 4 increasing reports of neurologic manifestations of covid-19 are emerging, but only a few cases of gbs associated with this virus have been established. gbs is an immune-mediated response, likely from a recent infection, where the immune system attacks the peripheral nerves due to a molecular mimicry phenomenon. this has preceded two-thirds of the times by an upper respiratory infection or gastroenteritis. the case series by mao et al in wuhan, china, was one of the first studies that showed neurologic manifestations in patients with covid-19. they concluded that patients with more severe covid-19 illness were more likely to have neurologic symptoms. 5 in contrast, our patient's respiratory status was relatively stable. in italy, a series of five patients were diagnosed with gbs 5-10 days after a viral illness from covid-19. similar to our patient, they did not show typical mri findings of gbs including surface thickening and contrast enhancement on the conus medullaris and the nerve roots of the cauda equina. only one of the five patients had a functional recovery to the point of ambulation. we cannot yet conclude the severity of neurologic injury with covid-19-associated gbs. 6 the literature shows there is variability in the presentation of covid-19 and gbs. our case had a typical course of viral symptoms preceding gbs findings. however, two other case reports identified concurrent respiratory and neurologic symptoms. 7 8 besides, the duration from onset of viral illness to neurologic manifestations have ranged from 5 to 24 days. 9 in all cases reported, treatment with ivig was administered. however, the recovery varied from full neurologic recovery to no change in extremity function and terminal respiratory failure. [7] [8] [9] [10] [11] [12] there are several theories on how the virus attacks the nervous system. studies postulate that the virus can infect a peripheral neuron, use an active retrograde transport mechanism across the synapse onto the cell body and reach the brain. 13 other proposed mechanisms include direct damage through angiotensin converting enzyme-2ace2 receptors, cytokinerelated injury and hypoxia-related sequela. 14 it is unclear if the covid-19 itself triggers the formation of antibodies again any specific forms of glycolipids seen in some forms of gbs. 15 there guillain-barré syndrome (gbs) should be considered in patients with peripheral nervous system symptoms. ► early recognition and treatment of gbs can prevent potentially serious morbidity and mortality in patients with covid-19. ► as we evaluate and review more patients with covid-19, our understanding of neurologic and postviral complications continues to grow. early transmission dynamics in wuhan, china, of novel coronavirus-infected pneumonia assessment of current diagnostic criteria for guillain-barr syndrome guillain-barré syndrome neurological manifestations of covid-19 and other coronavirus infections: a systematic review neurologic manifestations of hospitalized patients with coronavirus disease 2019 in wuhan, china guillain-barré syndrome associated with sars-cov-2 guillain-barré syndrome related to covid-19 infection guillain-barré syndrome associated with sars-cov-2 infection covid-19 may induce guillain-barré syndrome covid-19 and guillain-barré syndrome: more than a coincidence! revue neurologique guillain-barré syndrome following covid-19: new infection, old complication? guillain-barré syndrome associated with sars-cov-2 infection: causality or coincidence? evidence of the covid-19 virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms neurologic complications of covid-19 guillain barre syndrome associated with covid-19 infection: a case report is a need for further investigation into how covid-19 is related to gbs.contributors contributions were collaboratively made by all authors. these contributions include drafting the article, conception or design of the work, critical revision of the article and final approval of the version to be published. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. sindhuja korem http:// orcid. org/ 0000-0003-4647-4968 haresh gandhi http:// orcid. org/ 0000-0002-1835-2202 key: cord-296950-9dldbs6o authors: el-zein, rayan s; cardinali, serge; murphy, christie; keeling, thomas title: covid-19-associated meningoencephalitis treated with intravenous immunoglobulin date: 2020-09-06 journal: bmj case rep doi: 10.1136/bcr-2020-237364 sha: doc_id: 296950 cord_uid: 9dldbs6o a 40-year-old man presented with altered mental status after a recenthospitalisation for covid-19 pneumonia. cerebrospinal fluid (csf) analysis showed lymphocytosis concerning for viral infection. the csf pcr for sars-cov-2 was negative, yet this could not exclude covid-19 meningoencephalitis. during hospitalisation, the patient’s mentation deteriorated further requiring admission to the intensive care unit (icu). brain imaging and electroencephalogram (eeg) were unremarkable. he was, thus, treated with intravenous immunoglobulin (ivig) for 5 days with clinical improvement back to baseline. this case illustrates the importance of considering covid-19’s impact on the central nervous system (cns). haematogenous, retrograde axonal transport, and the effects of cytokine storm are the main implicated mechanisms of cns entry of sars-cov-2. while guidelines remain unclear, ivig may be of potential benefit in the treatment of covid-19-associated meningoencephalitis. a growing body of evidence is surfacing in regard to the neuroinvasiveness of covid-19. neurologic manifestations in patients infected with sars-cov-2 have been reported such as anosmia, ageusia, ataxia, seizures, haemorrhagic necrotising encephalopathy, and guillain-barré syndrome. [1] [2] [3] the neurotropism of covid-19 remains undefined, although, previous coronaviruses have been implicated to involve the central nervous system (cns). 4 herein, we present a case of a patient with altered sensorium diagnosed with covid-19associated meningoencephalitis. a 40-year-old hispanic man with no known medical history reported fevers, cough, and generalised fatigue in early april 2020 (day 1). on day 3, he presented to the emergency department and was confirmed to have covid-19 via detection of sars-cov-2 viral nucleic acid in a nasopharyngeal swab specimen using the simplexa sars-cov-2 assay (diasorin molecular llc, cypress, california, usa). he was subsequently hospitalised for 7 days for covid-19-associated pneumonia. he completed a regimen of hydroxychloroquine (200 mg every 12 hours for 5 days). one day after discharge (day 7), he returns to the hospital with altered mental status. the patient's son reported that he was responding to questions inappropriately, having visual hallucinations, and was forgetful. neurological examination revealed confusion with orientation only to self, inability to follow commands,and no apparent focal neurological deficits. otherwise, general examination was unremarkable and vital signs were within normal ranges (blood pressure 129/84 mm hg, heart rate 104 bpm, spo 2 98% on room air and 98.5°f oral temperature). after an unrevealing ct of the head, a lumbar puncture was performed. his cerebrospinal fluid (csf) was clear and colourless with an elevated csf cell count and lymphocytic predominance suspicious for viral encephalitis (table 1). the csf glucose (70 mg/ dl) was increased and csf protein levels (19 mg/ dl) were decreased. a csf pcr panel including cryptococcus neoformans/gattii, herpes simplex virus, varicella zoster virus, streptococcus pneumoniae, neisseria meningitidis and enterovirus was negative. the sars-cov-2 csf pcr was negative; however, a high index of suspicion remained due to the temporal relationship of his current symptoms and the recent covid-19 pneumonia. due to the patient's lack of risk factors, testing for tuberculous was not pursued, especially with the absence of an elevated csf protein and decreased csf glucose concentration. also, mycoplasma studies were not performed. an empiric meningitis regimen (ceftriaxone, vancomycin, acyclovir and steroids) was initiated and he was admitted to the medical ward with the clinical diagnosis of encephalitis. blood analysis revealed an elevated ferritin (1127 ng/ml), lactate dehydrogenase (ldh) (295 u/l), and c reactive protein (10.6 mg/l). these are decreased in comparison with 2 days prior during his recent hospitalisation (ferritin 1225 ng/ml, ldh 355 u/l and crp 58.2 mg/l). d-dimer was elevated at 1.42 µg/ml, which increased from 1.06 µg/ml. one day after admission (day 8), he was transferred to the intensive care unit (icu) for progressively worsening mental status with increased agitation; a dexmedetomidine infusion was initiated. mri of the brain did not reveal any significant alterations or contrastenhanced areas within the brain and/or meninges (figure 1). a routine electroencephalogram (eeg) showed diffuse slowing in the theta range indicative of encephalopathy and lacked any epileptogenic activity. to this end, autoimmune encephalitis was less likely due to the absence of bilateral brain mri new disease findings in addition to lack of epileptogenic or focal slowing observed on eeg. the antimicrobial regimen was deescalated; the csf gram stain and culture were negative. two days after admission (day 9), he was started on intravenous immunoglobulin (ivig) (0.4 g/kg) for 5 days. for concern of delay in viral clearance, glucocorticoids were avoided. within the next 2 days, his altered mentation progressively improved; he was oriented to time and place, able to communicate, and was following commands. he could not recall recent events of the hospital admission. on the third day of treatment, the patient was back at his baseline. after completion of ivig, at discharge, 7 days after admission (day 14), neurological examination was unremarkable. two months after discharge, via a telephone follow-up encounter, the patient denied any symptoms. his son denied any further mental status changes. our report describes a case of encephalitis associated with sars-cov-2 which showed clinical improvement with ivig therapy. there are only a few cases previously reported on the neurologic involvement of covid-19 with variable presentations, diagnostics and treatments. moriguchi et al 5 described what appears to be the first case of covid-19-associated meningoencephalitis presenting with convulsions and confirmed with a positive sars-cov-2 csf pcr; their patient had abnormal mri findings of the medial temporal lobe and was treated with favipiravir. the patient remained in icu at day 15 after onset of symptoms. another report described a case of covid-19associated necrotising encephalopathy with multiple haemorrhagic rim enhancing lesions on mri. 2 they used ivig as the mainstay therapy but the outcome remained undefined. paniz-mondolfi et al 6 reported a case of covid-19-associated pneumonia in a 74 years old with parkinson's who succumbed to his illness on day 11; however, sars-cov-2 was found in the brain capillary endothelium and neuronal cell bodies on postmortem examination. large studies pertaining to the incidence, diagnostics, and therapeutics of covid-19 neurologic manifestations remain lacking. a recent retrospective study showed that approximately 55 (25%) of 214 patients with covid-19 had manifestations of cns involvement with dizziness and headache being the most common. 1 csf analysis was not performed in this cohort. in another retrospective study by li et al, the incidence of cerebrovascular events in patients with covid-19 was about 5% with a median time of stroke after covid-19 diagnosis of 12 days. 1 as previously reported, 7 a subset of patients with covid-19 could have neurologic signs and symptoms without the typical respiratory symptoms. as more reports emerge, there is a newfound interest in elucidating the mechanisms of sars-cov-2 neurotropism. lessons from the taxonomically related sars-cov 8 in the past have supported haematogenous spread and retrograde neuronal transport as the proposed routes of sars-cov-2 neuroinvasion. sars-cov-2, through its interaction with ace2, could enter the cns given that ace2 is expressed in the vascular endothelium, neurons, and glial cells of the brain. 9 under electron microscopy, sars-cov-2 viral particles have been shown to be actively budding across endothelial cells of frontal lobe brain sections. 6 the cytokine storm associated with covid-19 may alter the permeability of the blood-brain barrier, thus further allowing entry. retrograde propagation along the olfactory tract has been shown to occur by sars-cov, and thus may explain the anosmia associated with sars-cov-2. 10 once within the cns, viral-induced cytokine storm and glial cell activation may result in immunologic response and inflammatory injury leading to encephalitis in our patient. although the csf pcr was negative, this could not definitely exclude the diagnosis because sars-cov-2 dissemination is transient and its csf titre may be extremely low, as shown in cases of west nile and enterovirus infections. 11 12 our successful use of ivig corroborates reporting of its possible benefit in covid-19 13 14 ; no specific guidelines regarding its use are released as of yet. considering the aforementioned inflammatory state undermining covid-19, ivig's proposed mechanism consists of the inhibition of innate immune cells, neutralization of activated complement, modulation of b cells and regulatory t cells, and the inhibition of cytokines. 15 figure 1 brain mri demonstrating normal mri findings on t2. ► covid-19 may involve the central nervous system irrespective of pulmonary involvement. ► the cerebrospinal fluid pcr for sars-cov-2 cannot be used definitively to exclude covid-19-associated meningoencephalitis. ► intravenous immunoglobulin may be of potential benefit in covid-19-associated meningoencephalitis. caution must be taken with its increased risk of thromboembolism especially given the reports of covid-19 hypercoagulability. currently, several randomised controlled trials evaluating the efficacy of high-dose ivig therapy in severe covid-19 have been initiated (nct04350580, nct04381858 and nct04261426). twitter rayan s el-zein @rayan_elzein acute cerebrovascular disease following covid-19: a single center, retrospective, observational study covid-19-associated acute hemorrhagic necrotizing encephalopathy: imaging features guillain-barré syndrome associated with sars-cov-2 infection: causality or coincidence? human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? a first case of meningitis/encephalitis associated with sars-coronavirus-2 central nervous system involvement by severe acute respiratory syndrome coronavirus -2 (sars-cov-2) potential neurological symptoms of covid-19 detection of severe acute respiratory syndrome (sars)-associated coronavirus rna angiotensin-converting enzyme 2 in the brain: properties and future directions severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ace2 encephalitis as a clinical manifestation of covid-19 case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium effect of regular intravenous immunoglobulin therapy on prognosis of severe pneumonia in patients with covid-19 high-dose intravenous immunoglobulin as a therapeutic option for deteriorating patients with coronavirus disease 2019 pharmaco-immunomodulatory therapy in covid-19 acknowledgements the authors would like to acknowledge members of the team who cared for the patient including neurologist, dr shnehal patel; intensivists, dr lucia chowdhury and dr harvinder gill and hospitalist, dr sudhir duvuru. contributors rse, sc and tk participated in the care of the patient. report was written by rse, sc and cm. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. rayan s el-zein http:// orcid. org/ 0000-0002-1437-7082 key: cord-309236-p4c2d5y3 authors: khurram, ruhaid; johnson, franklin t f; naran, revati; hare, samanjit title: spontaneous tension pneumothorax and acute pulmonary emboli in a patient with covid-19 infection date: 2020-08-11 journal: bmj case rep doi: 10.1136/bcr-2020-237475 sha: doc_id: 309236 cord_uid: p4c2d5y3 the covid-19 pandemic has had a significant impact on the structure and operation of healthcare services worldwide. we highlight a case of a 64-year-old man who presented to the emergency department with acute dyspnoea on a background of a 2-week history of fever, dry cough and shortness of breath. on initial assessment the patient was hypoxic (arterial oxygen saturation (sao(2)) of 86% on room air), requiring 10 l/min of oxygen to maintain 98% sao(2). examination demonstrated left-sided tracheal deviation and absent breath sounds in the right lung field on auscultation. a chest radiograph revealed a large right-sided tension pneumothorax which was treated with needle thoracocentesis and a definitive chest drain. a ct pulmonary angiogram demonstrated segmental left lower lobe acute pulmonary emboli, significant generalised covid-19 parenchymal features, surgical emphysema and an iatrogenic pneumatocoele. this case emphasises the importance of considering coexisting alternative diagnoses in patients who present with suspected covid-19. the covid-19 pandemic has had a significant impact on the structure and operation of healthcare services worldwide. we highlight a case of a 64-year-old man who presented to the emergency department with acute dyspnoea on a background of a 2-week history of fever, dry cough and shortness of breath. on initial assessment the patient was hypoxic (arterial oxygen saturation (sao 2 ) of 86% on room air), requiring 10 l/min of oxygen to maintain 98% sao 2 . examination demonstrated leftsided tracheal deviation and absent breath sounds in the right lung field on auscultation. a chest radiograph revealed a large right-sided tension pneumothorax which was treated with needle thoracocentesis and a definitive chest drain. a ct pulmonary angiogram demonstrated segmental left lower lobe acute pulmonary emboli, significant generalised covid-19 parenchymal features, surgical emphysema and an iatrogenic pneumatocoele. this case emphasises the importance of considering coexisting alternative diagnoses in patients who present with suspected covid-19. the novel severe acute respiratory syndrome coronavirus 2 (sars-cov-2) was first reported in december 2019 in wuhan, china and has now had a significant effect on populations worldwide in the form of the covid-19 pandemic. as of 4 june 2020, there have been 6 416 828 confirmed cases of covid-19 reported worldwide with 382 858 deaths, with an overall case fatality rate of approximately 6% 1 ; this has therefore led to a substantial burden on health and intensive care services. the presenting features reported are general and non-specific, including dry cough, fever, malaise, difficulty in breathing, and in severe cases profound hypoxaemia and cardiorespiratory arrest. in the early part of 2020, it has been a common presenting cause of significant hypoxia to the emergency department. despite its high prevalence, clinicians must ensure not to allow themselves to be distracted by this relatively new phenomenon, and to continue to practise good history taking and examination skills to identify coexisting, alternative potential life-threatening diagnoses and to provide optimal, timely treatment to patients. we exhibit a case of a 64-year-old man with suspected covid-19 pneumonia who presented acutely to the emergency department with tension pneumothorax and acute pulmonary emboli. a 64-year-old man presented to the emergency department with intermittent fevers, dry cough and progressive shortness of breath over a 2-week period. on the day of attendance, he acutely deteriorated with increased difficulty in breathing and pleuritic chest pain. his medical history included hypertension, type ii diabetes mellitus and hypercholesterolaemia. he had no known drug allergies and was taking simvastatin 20 mg once daily, ramipril 2.5 mg once daily and metformin 1 g two times per day as his regular medications. he is a socially independent man and a lifelong non-smoker with no pre-existing respiratory conditions and no significant family history. on examination, he was significantly breathless at rest with a respiratory rate of 30 breaths/min and an arterial oxygen saturation of 86% on air. oxygen saturations were stabilised at 98% on 10 l/ min of oxygen (60% fractional inspired oxygen (fio 2 )). other vital signs measured included a heart rate of 115 beats/min, blood pressure of 125/95 mm hg and temperature of 37.0°c. his trachea was deviated to the left and he had asymmetrical chest expansion (reduced on the right). chest auscultation revealed absent breath sounds throughout the right hemithorax and widespread crepitations on the left. heart sounds were unremarkable, abdomen was soft and non-tender with no organomegaly, and calves were non-tender bilaterally with no evidence of peripheral oedema. a portable chest radiograph in the emergency department demonstrated a large right-sided tension pneumothorax with mediastinal shift and diffuse airspace shadowing throughout the left lung, which was more pronounced peripherally (figure 1). a 12-lead ecg showed sinus tachycardia at a rate of 120 beats/min. arterial blood gas performed on fio 2 of 60% showed ph 7.44, partial pressure of oxygen (po 2 ) 8.06 kpa, partial pressure of carbon dioxide (pco 2 ) 4.46 kpa, bicarbonate (hco 3 ) 23.6 meq/l, base excess −0.8 mmol/l, glucose 7.4 mmol/l and lactate 1.8 mmol/l, in keeping with type 1 respiratory failure. routine blood test results on admission were as follows: haemoglobin: 129 g/l; white cell count: 11.2×10 9 /l; platelets: 538×10 9 /l; neutrophils: following initial management for the tension pneumothorax, a repeat chest radiograph demonstrated lung re-expansion with a small residual pneumothorax, but with no mediastinal shift; peripheral ground glass airspace opacities were accentuated, in keeping with covid-19 infection (figure 2). a ct pulmonary angiogram (ctpa) was performed on the second day of inpatient admission which highlighted multiple abnormalities contributing to this patient's hypoxia. there was evidence of acute segmental pulmonary emboli in the left lower lobe alongside generalised covid-19 alveolar opacities in the lower lobes. residual right-sided pneumothorax was visible alongside surgical emphysema as well as an iatrogenic secondary pneumatocoele, likely related to the depth of the chest drain tip (figure 3). the patient had a positive reverse transcriptase (rt)-pcr nasopharyngeal swab for covid-19. on recognition of the tension pneumothorax, the patient was initially treated with needle decompression with a large-bore, 14-gauge cannula inserted in the right second intercostal space in the mid-clavicular line. this was followed with a 12-french seldinger chest drain inserted into the 'triangle of safety' on the right side to achieve definitive management. the patient received supplemental oxygen to maintain target saturations of >94% and commenced on broad spectrum intravenous antibiotics (co-amoxiclav and clarithromycin) for treatment of superadded bacterial pneumonia. treatment dose low molecular weight heparin (tinzaparin sodium) was initiated for the pulmonary emboli visualised on ctpa. the chest drain was removed on day 3 of admission following the ctpa findings of iatrogenic pneumatocoele, and a repeat chest radiograph showed significant reinflation of the right lung with no residual pneumothorax. once oxygen saturations normalised without supplementary oxygen (96% on air), the patient was discharged after a 4-day admission with a 3-month course of apixaban 5 mg two times per day and follow-up in the anticoagulation clinic. he was reviewed in the outpatient ambulatory care clinic 5 days postdischarge; at this point, he remained normoxic and a repeat chest radiograph showed complete resolution of pneumothorax. however, right basal consolidation persisted, for which he received a further 1-week course of antibiotics ( figure 4) . he is now due for routine follow-up with the respiratory team in 4-6 months' time. he was advised to remain isolated until his symptoms resolved after discharge. this case outlines the importance of timely identification and treatment of other contributory reversible causes of hypoxia on a background of covid-19 infection. to our knowledge, we have reported the first documented case of a patient with covid-19 pneumonia presenting with both spontaneous tension pneumothorax and acute pulmonary emboli. the evolution of spontaneous pneumothorax 2 3 and pneumomediastinum 4-6 with concomitant covid-19 infection, prior to ventilation procedures, are rare entities, with very few cases reported in the literature. the rupture of subpleural bullae or pneumatocoeles is the most common cause of primary spontaneous pneumothorax, and risk factors for development include pre-existing chronic lung conditions, smoking, male gender and prolonged coughing. the precise mechanism of this phenomena in the context of covid-19 is not fully understood and a coincidental association cannot be excluded. however, studies have reported the presence of pneumatocoeles and cystic lung parenchymal features in patients with covid-19, 7 which may increase the chance of developing secondary pneumothoraces. several studies have reported the increased prevalence of thromboembolic events in covid-19 infection. [8] [9] [10] the systemic inflammation associated with covid-19 and endothelial dysfunction, along with the generated hypercoagulable state, are the likely contributory factors to the pathogenesis of acute pulmonary emboli. the viscosity of blood is further increased by the hypoxia from severe pneumonia. biomarkers such as elevated d-dimer, lactate dehydrogenase and ferritin levels are associated with a worse prognosis. 11 it is essential to therefore identify and treat thromboembolic events with timely anticoagulation along with stringent prevention strategies aiming at adequate thromboembolic prophylaxis with low molecular weight heparin. the current widely accepted and implemented method for the diagnosis of covid-19 is the rt-pcr, with a pooled sensitivity in meta-analyses reported to be of 89%. 12 however, a high false negative rate poses several clinical and social challenges. ct chest imaging is a useful evaluation tool reserved for assessing disease severity, progression, coexisting pathologies and complications. the classic radiological findings on ct are bilateral, peripheral ground glass opacifications, crazy-paving pattern, bronchovascular thickening and consolidation. 13 14 atypical ct findings reported include pleural effusions, mediastinal lymphadenopathy, pneumothoraces and cavitations, which raise the suspicion of superadded bacterial infection and are often more apparent during the later courses of the disease. 15 typical ct findings have also been observed on asymptomatic patients with covid-19. 16 using ct as a diagnostic or screening tool for covid-19 alone is discouraged by many radiological societies and institutions 17 due to recent meta-analyses showing a pooled high sensitivity and low specificity of 94% and 37%, respectively, as well as a high rate of false positives. 12 furthermore, routine use of ct poses risks, for example, increased ionising radiation and usage of finite personal protective resources between patients in the event of shortage. 18 nevertheless, ct imaging in the context of our case had considerable benefit in the identification of additional diagnoses, namely pulmonary emboli, as well as an assessment of the severity of infection. the rationale for using ctpa as opposed to ct thorax without contrast was due to local data from our centre showing that 34.5% of patients who were sars-cov-2-positive were diagnosed with pulmonary embolism as an inpatient, alongside an increasingly high number of readmissions with thromboembolism in previously discharged patients. 19 the identification of an iatrogenic pneumatocoele on ct assisted in the timely removal of the chest drain. there have been noticeable changes to the structure and operation of healthcare services in the fight against this pandemic. many trusts have adopted protocols and escalation pathways for patients with covid-19, which may risk patients being given incorrect and potentially dangerous treatment in the event of other coexisting pathologies. for example, protocol-driven prompt continuous positive airway pressure treatment without appropriate assessment in our patient with profound hypoxia would have been extremely detrimental to his condition. in the current climate, it is important for clinicians to maintain an individualised, thorough approach to patients presenting with symptoms of covid-19 and to exclude additional underlying pathologies in the interest of patient-centred care. ► spontaneous pneumothorax and acute pulmonary emboli are important coexisting respiratory pathologies to consider on a background of covid-19 infection. ► it is important to maintain an individualised approach to exclude additional underlying pathologies, which can be assisted with good history taking and examination skills. ► ct chest imaging can provide assistance with the assessment of coexisting pathologies, disease severity, progression and complications. contributors rk is the lead author in this case report and played a significant role in writing the manuscript, obtaining consent and following up the patient. ftfj contributed to writing the manuscript and clerked the patient in the emergency department. rn is a clinical fellow in respiratory medicine who was involved in the care of the patient and contributed to writing the manuscript. sh is a consultant chest radiologist who provided expert opinion, supervised and contributed to writing the manuscript. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. world health organisation coronavirus disease (covid-19) dashboard tension pneumothorax in a patient with covid-19 spontaneous pneumothorax and subcutaneous emphysema in covid-19 patient: case report spontaneous pneumomediastinum in covid-19 covid-19 with spontaneous pneumomediastinum sars-cov-2 pulmonary infection revealed by subcutaneous emphysema and pneumomediastinum covid-19 with cystic features on computed tomography: a case report acute pulmonary embolism in covid-19 related hypercoagulability severe pulmonary embolism in covid-19 patients: a call for increased awareness acute pulmonary embolism associated with covid-19 pneumonia detected by pulmonary ct angiography abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia diagnostic performance of ct and reverse transcriptasepolymerase chain reaction for coronavirus disease 2019: a meta-analysis clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china relation between chest ct findings and clinical conditions of coronavirus disease (covid-19) pneumonia: a multicenter study another decade, another coronavirus chest ct findings in cases from the cruise ship "diamond princess radiology department preparedness for covid-19: radiology scientific expert review panel chest ct and coronavirus disease (covid-19): a critical review of the literature to date a matter of time: duration and choice of venous thromboprophylaxis in patients diagnosed with covid-19 competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. ruhaid khurram http:// orcid. org/ 0000-0002-6987-6698 key: cord-279989-swsxez0a authors: sokolov, elisaveta; hadavi, shahrzad; mantoan ritter, laura; brunnhuber, franz title: non-convulsive status epilepticus: covid-19 or clozapine induced? date: 2020-10-04 journal: bmj case rep doi: 10.1136/bcr-2020-239015 sha: doc_id: 279989 cord_uid: swsxez0a we present a case of non-convulsive status epilepticus in a 57-year-old woman with a schizoaffective disorder, without an antecedent seizure history, with two possible aetiologies including sars-cov-2 infection and clozapine uptitration. we discuss the presentation, investigations, differential diagnosis and management. in particular, we focus on the electroencephalogram (eeg) findings seen in this case and the electroclinical response to antiepileptic medication. we review the literature and discuss the relevance of this case to the sars-cov-2 global pandemic. we emphasise the importance of considering possible neurological manifestations of sars-cov-2 infection and highlight seizure disorder as one of the possible presentations. in addition, we discuss the possible effects of clozapine on the electroclinical presentation by way of possible seizure induction as well as discuss the possible eeg changes and we highlight that this needs to be kept in mind especially during rapid titration. we present a case of non-convulsive status epilepticus in a 57-year-old woman with a schizoaffective disorder, without an antecedent seizure history, with two possible aetiologies including sars-cov-2 infection and clozapine uptitration. we discuss the presentation, investigations, differential diagnosis and management. in particular, we focus on the electroencephalogram (eeg) findings seen in this case and the electroclinical response to antiepileptic medication. we review the literature and discuss the relevance of this case to the sars-cov-2 global pandemic. we emphasise the importance of considering possible neurological manifestations of sars-cov-2 infection and highlight seizure disorder as one of the possible presentations. in addition, we discuss the possible effects of clozapine on the electroclinical presentation by way of possible seizure induction as well as discuss the possible eeg changes and we highlight that this needs to be kept in mind especially during rapid titration. the covid-19 pandemic has had an unprecedented impact on global health. we illustrate one of the less reported possible manifestations of the sars-cov-2 infection in order to bring further awareness to one of the probable neurological implications of this infection. we describe a case of non-convulsive status epilepticus (ncse) in a 57-year-old woman, without an antecedent seizure history. we highlight seizure disorders as a possible manifestation of sars-cov2 infection and describe the complexity of these presentations in the intensive care setting, especially in the context of atypical antipsychotics such as clozapine. a 57-year-old right-handed woman presented with shortness of breath and fever in mid april 2020. the patient was lethargic and too breathless to provide a history of the events leading up to admission. a collateral history was taken from her sister who explained that she had become nonverbal in the week prior to admission and had been increasingly breathless. for the previous 18 months she had resided in a mental health hospital being treated for schizoaffective disorder. her medical history includes depression, pancreatectomy, splenectomy (for which she is on long-term antibiotics), and chronic obstructive pulmonary disease. she has a long smoking history (40 pack/years). prior to admission, she had a good exercise tolerance and despite having inhalers, rarely used them. she had a pulmonary embolism in october 2019, which was provoked after a traumatic fall sustaining multiple fractures. she had type 2 diabetes mellitus, which was managed with metformin and insulin. she had also reported episodes of mutism and unresponsiveness (lasting several days at a time). these events were considered to be related to her mental health disease. on examination at presentation, she was saturating at 91% on 40% oxygen and was unable to speak due to breathlessness. her respiratory rate was 22 breaths per minute and she was hypotensive. an arterial blood gas indicated a type 1 respiratory failure (pa02 7.2 kpa and pac02 4.0 kpa). her glasgow coma score (gcs) was seven (withdrawing and opening eyes to pain, without a verbal response). she was transferred to intensive care for intubation and ventilation the day after admission. she was treated with antibiotics to cover a community-acquired pneumonia and treated for an epstein-barr viraemia. she was nursed prone for acute respiratory distress syndrome. she developed an acute kidney injury for which she required haemofiltration. she was intubated and ventilated for one month. her sedation was gradually lightened as she was weaned off the ventilator. her gcs was 15 by the 25th of may and she was self-ventilating. she was weak in all four limbs. two days later she was less engaged, she was unable to speak or obey commands and opened her eyes only to pain. some new onset intermittent right-sided facial jerks were noted. she was diagnosed with ncse on electroencephalogram (eeg). she was commenced on levetiracetam. during the next 12 hours, her gcs improved to 14, she was opening her eyes spontaneously, and obeyed motor commands; however, was not completely oriented to time or place and a repeat eeg confirmed a resolution of the status epilepticus (figure 1). she underwent several investigations during her admission. nasopharyngeal and oropharyngeal swab specimens were obtained and real-time pcr (rt-pcr) assay was performed, which tested positive for sars-cov-2. she had a ct brain scan without contrast which demonstrated bilateral calcification of the globus pallidus in keeping with mild age-related changes. an mri brain scan was normal. these two scans were done when the findings that shed new light on the possible pathogenesis of a disease or an adverse effect patient was noted not to be waking following extubation, first as she was quadriplegic at this time and second to consider if there were any mri features known to be associated with covid-19. at day ten postextubation, she underwent an eeg. frequent (2.5-4 hz), florid bilateral, non-synchronous epileptiform discharges were seen over both hemispheres throughout most of the recording. the patient was unresponsive during this period of recording. 2mg of intravenous lorazepam was given, after which the epileptiform discharges subsided and a 6-7 hz background predominated. the patient became slightly more alert, in that she could obey some motor commands and vocalise to a small extent. the eeg findings were in keeping with ncse with clear electroclinical improvement after lorazepam administration (figure 1a). one day later, she had another eeg study to investigate whether there were residual subclinical seizures. the eeg showed a background rhythm reaching 7-8 hz, which was reactive to external stimulation. frequent multifocal epileptiform discharges were seen as well as intermittent frontotemporal theta/delta waves. there was a significant improvement compared with the first eeg study. there was no evidence to suggest ncse; however, frequent epileptiform discharges were seen over both hemispheres, without a clear focus ( figure 1b) . we consider whether the ncse was indeed precipitated by sars-cov-2 infection, or whether it may have been clozapine induced. after being diagnosed with ncse, the patient was initially loaded on levetiracetam and then continued on 500 mg twice daily. during her admission, her regular clozapine dose of 150 mg in the morning and 300 mg at night was held. this was gradually reintroduced by psychiatry in increments during the first six weeks of her stay. at the time of onset of her facial jerks and lower gcs, she was taking 100 mg in the morning and 175 mg at night. this was then reduced abruptly the following day to 125 mg at night only, and the following day, when the eeg confirmed ncse, she was prescribed clozapine 50 mg two times per day (figure 2). the patient gradually improved in that she was able to verbalise and obey motor commands. she still however had episodes of fluctuating confusion three weeks after being discharged to the neurology ward; however, she did have a concomitant urinary tract infection at that time. covid-19 is of critical concern worldwide not only for its rapid transmission but also for its relatively heterogeneous presentation. the coronaviruses including sars-cov-2 have been reported to have neuroinvasive properties. sars-cov-2 is thought to be able to access cells that display the angiotensinconverting enzyme 2 (ace-2), which is expressed on both glial cells and neurons. 1 2 various neurological presentations have been linked to sars-cov-2, including encephalitis. 3 we describe a sars-cov-2 positive case presenting with ncse and discuss the possible aetiologies. in terms of our patient's psychiatric history, her schizoaffective disorder had been stable for the past few years following the introduction of clozapine. clozapine is an atypical antipsychotic, widely used for its superior efficacy in the management of treatment-resistant schizophrenia and schizoaffective disorder. its superior efficacy over other antipsychotics has been confirmed by multiple studies 4 and it is therefore widely used despite its numerous side effects. our patient's clozapine was stopped on admission and then uptitrated, and reduced quickly when she was found to be in ncse ( figure 2) . clozapine can interact with general anaesthetics potentiating central nervous findings that shed new light on the possible pathogenesis of a disease or an adverse effect system depression and a subsequent slow emergence from anaesthesia. this may be one contributor to our patient's variable recovery post extubation. a notable adverse effect of clozapine is precipitation of seizures, which have been observed at all stages of clozapine treatment, hence the reason why her clozapine was weaned rapidly over five days at the time that the patient dropped her gcs and presented with facial jerks. at the time of detection of ncse on eeg, her dose was 50 mg twice daily and she was not toxic (figure 2). seizures have been observed at low doses during the titration phase and at high doses during the maintenance phase of clozapine. 5 6 as many as eight percent of patients taking clozapine have focal or generalised seizures; however, there is no robust evidence for clozapine-induced ncse currently in the literature. the average time to develop seizures after clozapine initiation is reportedly between 34 and 42 days. 4 it is important to note that clozapine can impact the eeg. varma et al 7 described that of 565 patients on clozapine, 347 had an abnormal eeg. there is no clear evidence describing the effects of intravenous lorazepam on clozapine-induced epileptiform discharges. however, as we generally consider these discharges to be interictal, we do not predict benzodiazepines to have a modifying effect on them, rather we would expect an abundance of fast activity. several reports have been published associating sars-cov-2 with new onset seizures. six early case reports from the covid-19 pandemic have reported seizures as a manifestation of the infection. these accounts range from single generalised tonic-clonic (gtcs) seizures, 8 9 multiple gtcs, multiple focal seizures and one case of status epilepticus, described as ongoing myoclonic activity of the right face and limbs. [9] [10] [11] [12] the average age of the patients was 49 years (range 24-78 years). two cases were from the usa, and other reports came from italy, iran, japan and germany. in five out of the six patients, there was no prior history of seizures or a family history of epilepsy. all initially developed symptoms of sars-cov-2 (including fever, dry cough, fatigue, myalgia) and subsequently had seizures during their clinical course. all six tested positive for covid-19, but only two patients had cerebrospinal fluid (csf) pcr tested for sars-cov-2, one being positive. the mri in this patient displayed the radiological features of encephalitis. 13 our patient's eeg pattern is in keeping with the salzburg criteria for ncse in that the epileptiform discharges were at a frequency of ≤2.5/s and there was electroclinical improvement with application of intravenous benzodiazepine. we conclude that the two most likely aetiologies for her ncse include either sars-cov-2 infection and/or the reintroduction and relatively rapid uptitration of clozapine. the patient did not undergo a lumbar puncture however as she was clinically improving with antiepileptic treatment and this investigation could not be clinically justified. we could not therefore demonstrate the presence of sars-cov-2 in the csf. we hypothesise that sars-cov-2 could trigger seizures through a neurotropic pathogenic mechanism and subsequently emphasise the importance of considering possible neurological manifestations, including seizure disorder of sars-cov-2 infection. in addition, atypical antipsychotics such as clozapine can induce both seizures and eeg changes and this needs to be kept in mind especially in rapid titration in the itu setting. ncse has not previously been described in the setting of clozapine uptitration and we present this as a possible alternative aetiology in this case. ► we emphasise the importance of considering possible neurological manifestations of sars-cov-2 infection. ► there is emerging evidence associating sars-cov-2 with seizure disorders. ► atypical antipsychotics such as clozapine can induce both seizures and eeg changes and this needs to be kept in mind especially during rapid titration in the intensive care unit (itu) setting. contributors all authors including es, sh, lm and fb take full responsibility for the data collection, the analyses and interpretation of the data, and the conduct of the research. all four authors listed above contributed to the data analysis and interpretation, the conduct of the research and the discussion and conclusions outlined within the article.the corresponding author (es) has full access to all of the data; and the author has the right to publish any and all data separate and apart from any sponsor. all authors and contributors have agreed to conditions noted by bmj case reports. consent forms from all participant in this study have been received and they are on file in case they are requested by the editor. the work described is consistent with the journal's guidelines for ethical publication. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. a pneumonia outbreak associated with a new coronavirus of probable bat origin evidence of the covid-19 virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms covid-19-associated mild encephalitis/ encephalopathy with a reversible splenial lesion evidence of clozapine's effectiveness in schizophrenia: a systematic review and meta-analysis of randomized trials seizures during clozapine therapy clinical review of clozapine treatment in a state hospital clozapine-related eeg changes and seizures: dose and plasma-level relationships a first case of meningitis/encephalitis associated with sars-coronavirus-2 encephalopathy and seizure activity in a covid-19 well controlled hiv patient frequent convulsive seizures in an adult patient with covid-19: a case report covid-19 presenting with seizures first case of focal epilepsy associated with sars-coronavirus-2 focal status epilepticus as unique clinical feature of covid-19: a case report provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. elisaveta sokolov http:// orcid. org/ 0000-0002-1509-9416copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-257839-kfzc4pwq authors: ferguson, katie; quail, nathaniel; kewin, peter; blyth, kevin g title: covid-19 associated with extensive pulmonary arterial, intracardiac and peripheral arterial thrombosis date: 2020-08-03 journal: bmj case rep doi: 10.1136/bcr-2020-237460 sha: doc_id: 257839 cord_uid: kfzc4pwq we describe a patient with covid-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. a 58-year-old man, without major comorbidity, was admitted with a 14-day history of breathlessness. severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection was confirmed by laboratory testing. initial imaging revealed covid-19 pneumonia but no pulmonary thromboembolism (pte) on ct pulmonary angiography (ctpa). the patient subsequently developed respiratory failure and left foot ischaemia associated with a rising d-dimer. repeat ctpa and lower limb ct angiography revealed simultaneous bilateral pte, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. this case highlights a broad range of vascular sequalae associated with covid-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation. we describe a patient with covid-19 who developed simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. a 58-year-old man, without major comorbidity, was admitted with a 14-day history of breathlessness. severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection was confirmed by laboratory testing. initial imaging revealed covid-19 pneumonia but no pulmonary thromboembolism (pte) on ct pulmonary angiography (ctpa). the patient subsequently developed respiratory failure and left foot ischaemia associated with a rising d-dimer. repeat ctpa and lower limb ct angiography revealed simultaneous bilateral pte, biventricular cardiac thrombi and bilateral lower limb arterial occlusions. this case highlights a broad range of vascular sequalae associated with covid-19 and the fact that these can occur despite a combination of prophylactic and treatment dose anticoagulation. covid-19 is the clinical syndrome associated with severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection. although respiratory failure is the most apparent feature of the disease, venous and arterial thrombosis are well-recognised sequalae. [1] [2] [3] [4] expert guidance currently recommends higher than standard doses of prophylactic anticoagulation for patients with covid-19 requiring critical care. [1] [2] [3] [4] we are not aware of any previously reported cases of covid-19 associated with simultaneous pulmonary, intracardiac and peripheral arterial thrombosis. we present this case to highlight the extensive covid-19-associated thrombotic complications that can occur, even despite periods of high-dose prophylactic and therapeutic anticoagulation. a 58-year-old man presented with a 14-day history of intermittent fever and worsening shortness of breath on exertion. no history of chest pain was reported. the patient's medical history was limited to well-controlled hypertension, obesity (body mass index of 31 kg/m 2 on admission) and a spiral fracture of the right tibia and fibula 15 years previously, with no residual indwelling prosthetic material. there was no history of angina, venous thrombosis peripheral vascular disease. pre-admission medications included amlodipine 10 mg once daily, indapamide 2.5 mg once daily and candesartan 4 mg once daily. the only family history of note was of maternal deep vein thrombosis provoked by pregnancy. the patient was an office worker but reported good functional status, regularly walking and swimming for recreation. he reported a smoking history of less than a single pack-year of cigarette consumption and approximately 24 units of alcohol per week. initial clinical examination was unremarkable except for a notable oxygen requirement. a fraction of inspired oxygen (fio 2 ) of 0.35 was required to maintain a peripheral oxygen saturation above 90%. an initial chest radiograph revealed bilateral intrapulmonary opacities consistent with covid-19 pneumonia, and sars-cov-2 infection was subsequently confirmed by reverse transcription pcr, based on a nasopharyngeal swab. initial prothrombin time (pt) and activated partial thromboplastin time (aptt) were normal and c-reactive protein (crp) was high (405 mg/l (0-10 mg/l)). d-dimer was significantly elevated at 508 ng/ml (0-230 ng/ml), prompting initiation of empirical treatment dose low molecular weight heparin (lmwh) pending ct pulmonary angiography (ctpa). this subsequently confirmed bilateral peripheral ground glass opacification (ggo), consistent with covid-19 pneumonia, and mild coronary artery calcification. no pulmonary thromboembolism (pte) was present. lmwh dosing was, therefore, reduced to a standard prophylactic regime for venous thromboembolism (vte) (enoxaparin 40 mg once daily) on day 2. on day 3, the patient developed an increasing oxygen requirement (fio 2 now 0.4) and was transferred to the high dependency unit (hdu) for consideration of continuous positive airway pressure (cpap). admission to hdu prompted an empirical increase in vte prophylaxis dose (to enoxaparin 40 mg two times per day). this was based on recently published expert opinion advocating higher dose thromboprophylaxis in patients with covid-19 perceived to be at higher vte risk, including those transferred to critical care or requiring cpap. 4 despite this, the patient developed a cold and painful left foot on day 4. on examination, dorsalis pedis and posterior tibial pulses were findings that shed new light on the possible pathogenesis of a disease or an adverse effect absent on the left. there was some loss of sensation; however, power appeared unaffected. d-dimer levels were noted to have risen to 992 ng/ml, while aptt and pt remained normal. fibrinogen and platelet counts were slightly elevated (4.5 g/l (1.70-4.00 g/l) and 441×10 9 /l (150×10 9 -410×10 9 /l), respectively) but troponin i was normal (6 ng/l (0-34 ng/l) and crp was trending down. a clinical diagnosis of arterial embolism was made, prompting a return to treatment dose anticoagulation. unfractionated heparin (ufh) was initially prescribed, followed by oral apixaban. lower limb ct angiography was not performed at this point following discussion with vascular surgery, since the limb was deemed viable and a conservative approach was felt to be optimal. the patient's respiratory function stabilised after a short period of awake proning. cpap did not need to be used. he was stepped down to the respiratory unit on day 6. by day 9, the patient still had a persistent moderate oxygen requirement (fio 2 : 0.35-0.4) and presented with a cold, painful left great toe. d-dimer levels were noted to be steadily rising (now 3449 ng/ml), but serial coagulation screens and troponin levels were normal. the platelet count fell to 219×10 9 /l. repeat ctpa and bilateral lower limb ct angiography were performed and key images are presented in figure 1 . the ctpa revealed bilateral segmental and subsegmental occlusive pte with associated right ventricular strain (right ventricle to left ventricle ratio >1), large filling defects in the right and left ventricles consistent with biventricular thrombi and increasingly dense and confluent peripheral ggo, in keeping with the diagnosis of covid-19. an echocardiogram was performed, which showed no intracardiac defect nor ventricular dysfunction. the lower limb ct angiography demonstrated a small left posterolateral endoluminal aortic thrombus, complete occlusion of the right tibioperoneal trunk extending into the proximal peroneal and posterior tibial arteries, and occlusion of the tibioperoneal trunk on the left, distal to occlusion of the popliteal artery just below the level of the knee joint. furthermore, occlusion of the left anterior tibial artery, peroneal artery and multi-level occlusion of the posterior tibial artery was also demonstrated. additional clot was observed in the left plantar arch. the most striking feature of this case is the development of multiple thromboses, despite periods of appropriate prophylactic and therapeutic lmwh. initially, ufh was initiated to treat his suspected ischaemic limb. however, a falling platelet count raised the possibility of heparin-induced thrombocytopenia (hit). this could have potentially explained the breakthrough thrombosis demonstrated on the second ctpa, but hit was quickly ruled out by antibody screen. after consultation with haematologist colleagues, warfarin was selected as definitive, long-term anticoagulation, with an elevated international normalised ratio (inr) target (2.5-3.5). the patient was successfully discharged home on day 19. a duplex scan of the left lower leg was performed 2 weeks after discharge. this demonstrated ongoing occlusions of the left distal popliteal artery and tibioperoneal trunk. the posterior tibial artery remained occluded at the level of the ankle. on a positive note, there was recanalisation of the peroneal and anterior tibial arteries. the patient was deemed a good candidate for endovascular treatment but a conservative approach will be taken at present due to the recent acute illness and reduced service capacity during the covid-19 outbreak. at telephone follow-up, 1 month following discharge, the patient is managing to walk 2 km/day, but still reports some dyspnoea when walking uphill. he has ongoing intermittent pain and paraesthesia of the left foot, but this is improving and will be followed up by the vascular team. covid-19 infection causes hypoxaemia and a significant inflammatory response. these factors combined with reduced mobility contribute to high thromboembolic risk. 5 in addition, sars-cov-2 binds to the host's ace2 receptor. this is widely expressed on vascular endothelial cells, as well as the respiratory tract, providing a direct route for vascular viral cytopathic effects and promotion of proinflammatory and procoagulant processes that could drive vascular injury, atherosclerosis and occlusion. 5 in the case described here, diffuse thromboembolic complications developed despite higher dose vte prophylaxis and periods of treatment dose anticoagulation prompted by clinical suspicion. this suggests that alternative thromboprophylaxis strategies may need to be considered to address these important complications of covid-19. d-dimers are degradation products of fibrin cross-linked by factor xiiia, and may be elevated due to thrombosis, disseminated intravascular coagulation or secondary processes, including infection, pregnancy, recent trauma, and are frequently raised in the high dependency setting. in the case described here, d-dimer levels rose steadily throughout the admission and appeared to track the evolution of diffuse thromboembolism. in recent case series, elevated d-dimer levels were reported in 43% 6 of the patients and were associated with disease severity and increased mortality. 5 6 zhou et al observed that a d-dimer level greater than 1.0 μg/ml on admission (equivalent to 1000 ng/ml) was associated with an or for mortality of 18.42 (2.64-128.55, p=0.003) compared with patients with levels below 1.0 μg/ml. 5 findings that shed new light on the possible pathogenesis of a disease or an adverse effect several case series exist which explore the incidence of venous and arterial thrombosis in patients with covid-19. in a cohort of 198 hospitalised patients with covid-19 in the netherlands, middeldorp et al describe a 21-day vte incidence rate of 59% in patients treated in the intensive care unit (icu) and 9% in patients being treated on the wards, despite vte prophylaxis. 1 no distal arterial nor cardiac thromboses are reported in this series. another dutch study, in contrast, reported ischaemic strokes in 3.7% (95% ci 0% to 8.2%) of 184 icu patients with covid-19, 2 while a small italian series reported 4 cases of acute limb ischaemia-2 of which occurred in young patients without comorbidity. 7 a separate report from italy also described an increased incidence of acute limb ischaemia (defined as the proportion of all vascular interventions that were performed for acute limb ischaemia) between january 2020 and march 2020 compared with the same period in 2019 (22/141 (16.3%) vs 3/63 (1.8%), p<0.001), and reported a higher rate of revascularisation failure in these cases which were secondary to covid-19. 8 the binding of sars-cov-2 to vascular endothelial ace2 receptors might explain the occurrence of distal arterial thrombosis in patients without preceding vascular disease via viral replication within the endothelium, inflammatory cell infiltration and development of a distinct sars-cov-2 viral endotheliitis. 9 this process might also generate virus-loaded endothelial microparticles, which could provide a vehicle for further haematogenous viral spread and the propagation of endothelial injury. our patient was independently mobile throughout his hospital stay and, therefore, had no physical therapy input. however, physical therapy input should be encouraged in this patient's group, where the risk of thromboembolism is high and hospital stays are often prolonged. the high incidence of thrombotic complications in covid-19 has prompted some groups to recommend high-dose thromobprophylaxis, for example, lmwh two times per day. [1] [2] [3] [4] this regime is supported by practices in other high-risk settings, such as orthopaedic surgery and by limited observational data using laboratory surrogates. 10 the latter includes a study of 10 icu patients with covid-19 pneumonia in whom d-dimer levels and viscoelastic measures reduced in response to increased prophylactic dosing. 10 however, it remains unproven whether such a strategy will translate into improved patient outcomes and acceptable bleeding risks. the current case highlights the importance of severe prothrombotic states in patients with covid-19 and the urgent need for randomised clinical trials testing a range of prophylactic strategies. these may include antiviral therapies, immunomodulators and agents capable of stabilising endothelial dysfunction, such as a statins and ace inhibitors. [11] [12] [13] twitter nathaniel quail @drnatquail and kevin g blyth @kevingblyth acknowledgements dr joe sarvesvaran's care and compassion were integral to this patient's journey to recovery and we would like to acknowledge his support with writing this case report, and for selecting the key images to include. contributors nq and kf contributed equally to writing this paper. kgb contributed to intellectual content of the case report and had overall supervision of the writing. pk provided support in writing the case and looked after the patient in hospital. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer reviewed. this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. i was unwell at home with flu-like symptoms and was selfmedicating with paracetamol. after much cajoling from my family, i visited hospital and was admitted. at that time, i did not feel too unwell and even when transferred to high dependency unit (hdu), i did not realise how ill i was. i was in hdu twice, saw multiple medical teams and received an exemplary level of care. i had multiple visits to the imaging department and had several ultrasound scans while in bed. i am sure that the treatment that i received saved my life. what was apparent to me was that my condition was changing rapidly and unexpectedly, and the doctors involved with my care seemed to make the correct choices and decisions at each turn. ► covid-19 is associated with high thrombotic risk. ► current prophylactic anticoagulation strategies may not confer sufficient protection. ► clinicians should be wary of false reassurance of prophylactic anticoagulation in this patient group. ► there is an urgent need for randomised control trials to test novel prophylactic strategies. incidence of venous thromboembolism in hospitalized patients with covid-19 incidence of thrombotic complications in critically ill icu patients with covid-19 venous and arterial thromboembolic complications in covid-19 patients admitted to an academic hospital in the british thoracic society. bts guidance on venous thromboembolic disease in patients with covid-19 clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study clinical characteristics of 140 patients infected with sars-cov-2 in wuhan acute limb ischaemia in two young, nonatherosclerotic patients with covid-19 acute limb ischemia in patients with covid-19 pneumonia endothelial cell infection and endotheliitis in covid-19 the procoagulant pattern of patients with covid-19 acute respiratory distress syndrome effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients angiotensin-converting enzyme inhibition improves vascular function in rheumatoid arthritis anti-tumor necrosis factor-alpha treatment improves endothelial function in patients with rheumatoid arthritis katie ferguson http:// orcid. org/ 0000-0001-9308-6875 nathaniel quail http:// orcid. org/ 0000-0002-4918-5179 kevin g blyth http:// orcid. org/ 0000-0003-2972-6641 copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-291642-xfkdxnfb authors: howley, fergal; o'doherty, laura; mceniff, niall; o'riordan, ruth title: late presentation of ‘lemierre’s syndrome’: how a delay in seeking healthcare and reduced access to routine services resulted in widely disseminated fusobacterium necrophorum infection during the global covid-19 pandemic date: 2020-10-10 journal: bmj case rep doi: 10.1136/bcr-2020-239269 sha: doc_id: 291642 cord_uid: xfkdxnfb the sars-cov-2 outbreak has disrupted the delivery of routine healthcare services on a global scale. with many regions suspending the provision of non-essential healthcare services, there is a risk that patients with common treatable illnesses do not receive prompt treatment, leading to more serious and complex presentations at a later date. lemierre’s syndrome is a potentially life-threatening and under-recognised sequela of an oropharyngeal or dental infection. it is characterised by septic embolisation of the gram-negative bacillus fusobacterium necrophorum to a variety of different organs, most commonly to the lungs. thrombophlebitis of the internal jugular vein is frequently identified. we describe an atypical case of lemierre’s syndrome involving the brain, liver and lungs following a dental infection in a young male who delayed seeking dental or medical attention due to a lack of routine services and concerns about the sars-cov-2 outbreak. the sars-cov-2 outbreak has disrupted the delivery of routine healthcare services on a global scale. with many regions suspending the provision of non-essential healthcare services, there is a risk that patients with common treatable illnesses do not receive prompt treatment, leading to more serious and complex presentations at a later date. lemierre's syndrome is a potentially life-threatening and under-recognised sequela of an oropharyngeal or dental infection. it is characterised by septic embolisation of the gramnegative bacillus fusobacterium necrophorum to a variety of different organs, most commonly to the lungs. thrombophlebitis of the internal jugular vein is frequently identified. we describe an atypical case of lemierre's syndrome involving the brain, liver and lungs following a dental infection in a young male who delayed seeking dental or medical attention due to a lack of routine services and concerns about the sars-cov-2 outbreak. fusobacterium necrophorum is an anaerobic gram-negative rod. though commonly found in the oropharyngeal flora of healthy individuals, it has potential to cause severe localised and disseminated infection, including the eponymous 'lemierre's syndrome'. 1 though no strict definition of lemierre's syndrome is agreed on, most publications agree it includes a recent oropharyngeal infection, clinical or radiological evidence of internal jugular vein (ijv) thrombosis and isolation of an anaerobic pathogen (mainly f. necrophorum). population-based studies suggest that f. necrophorum most commonly affects young, otherwise healthy individuals. 1 2 the median age of onset is 19-22 years affecting two times as many males as females. described as 'life-threatening but curable', lemierre's syndrome has a mortality rate of 4%-12%. 2 reported incidence of lemierre's syndrome has increased in recent years. [2] [3] [4] the increasing incidence of this previously 'forgotten' disease is thought to be due to antimicrobial stewardship efforts resulting in decreased antibiotic prescribing for upper respiratory tract infections, 3 while improving laboratory techniques may also be contributing to an increased detection rate. 4 with many countries imposing travel warnings, restrictions of movement and lockdowns during the sars-cov-2 pandemic, emerging data suggest a delay in patients seeking care for urgent conditions. 5 furthermore, postponement of routine outpatient visits and elective procedures risks delaying diagnostic and therapeutic interventions, with severe impact on patients' health. 6 at a time when the sars-cov-2 outbreak has disrupted the provision of routine healthcare services on a national and global scale, we describe a delayed presentation of disseminated f. necrophorum infection in an immunocompetent young male, in a case that emphasises the importance of encouraging patients to seek urgent medical care during a pandemic. a 24-year-old man presented to the emergency department during the outbreak of the sars-cov-2 pandemic. he reported a 3-week history of headache, myalgia, left lower limb weakness, abdominal pain and anorexia. he also described shortness of breath, unstable gait (requiring assistance to walk) and right elbow pain. three weeks prior to presentation, he had experienced periodontal swelling and tenderness, which he described as a 'dental abscess'. he had not sought dental services at this time, and had subsequently delayed seeking medical attention, citing concerns about attending hospital due to the risk of contracting sars-cov-2. he had no medical history of note, but had undergone extensive dental procedures as a teenager (fillings to lower molars and dental extraction). he was heterosexual with no history of high-risk sexual activity and had no history of intravenous drug misuse. on examination, he was tachypnoeic, tachycardic, normotensive and afebrile. oxygen saturations were well-maintained on room air. examination of the thorax revealed right basal crepitations with no cardiac murmurs. neurological examination revealed left lower limb weakness and dysarthric speech. the abdomen was tense with no focal tenderness. the right elbow was markedly swollen and tender, with reduced range of movement. oral examination revealed marked tooth decay of the left lower molars, with no tonsillar enlargement or pharyngitis. no neck swelling or tenderness was reported. laboratory investigations revealed a microcytic anaemia (haemoglobin 99 g/l), thrombocytopenia (104×10 9 /l) and normal white cell count with lymphopenia (0.5×10 9 /l). liver function tests were markedly deranged (aspartate transaminase 120 iu/l, alanine transaminase 103 iu/l and bilirubin 37 µmol/l) with hypoalbuminaemia (25 g/l). inflammatory markers including c-reactive protein (194 mg/l), ferritin (979 µg/l) and d-dimer (1987 ng/ml) were markedly elevated. ct of the thorax, abdomen and pelvis revealed multifocal hepatic lesions consistent with disseminated hepatic abscesses and multiple foci throughout the lungs in keeping with septic emboli ( figure 1) . ct of the brain demonstrated multiple foci of hypoattenuation in the brain parenchyma suspicious for cerebral abscesses (figure 2). transthoracic echocardiogram (tte) showed no vegetation but a patent foramen ovale was noted. sars-cov-2 swab and blood-borne viral screening were negative, while mri of the brain demonstrated multifocal abscesses in both cerebral hemispheres (figure 3). initial ct angiogram of the neck revealed bilateral dental abscesses but no neck collection or abscess, and no filling defect within the vasculature. however, a subsequent ct angiogram during the course of the admission revealed a filling defect within the left internal jugular vein (figure 4). no further filling defects were identified within the surrounding vasculature, including the lingual and tonsillar veins. a transesophageal echocardiogram was not performed given the unremarkable tte and confirmation of an alternative source of infection, coupled with hospital-wide efforts to limit aerosolising procedures during the sars-cov-2 pandemic. at the time of admission under the general medical team, differentials under consideration included infective endocarditis, sars-cov-2 infection with superimposed bacteraemia and hiv with an associated opportunistic infection. the possibility of a disseminated sexually transmitted infection, septic arthritis or an underlying malignancy was also considered. intravenous antibiotics including ceftriaxone, vancomycin and metronidazole were commenced following collection of three sets of blood cultures. intravenous fluids were administered. consultation was sought from orthopaedic and maxillofacial surgical teams, as well as infectious disease, cardiology and haematology specialists. within 24 hours, a gram-negative bacillus was confirmed in the anaerobic blood culture bottle, subsequently identified as f. necrophorum. on day 2 of admission, our patient was transferred to the intensive care unit (icu) for surveillance. on day 4, his clinical status deteriorated, developing type one respiratory failure and requiring intubation. he remained intubated for 18 days, during figure 2 ct imaging of the brain demonstrating foci of hypoattenuation in the brain parenchyma. which the time he underwent interventional radiology guided drainage of liver abscesses and dental extraction of two retained dental roots and six decayed teeth on both sides of the mouth. therapeutic dose enoxaparin was initiated following detection of the filling defect within the left internal jugular vein, before switching to apixaban prior to discharge. after 3 weeks in icu and a further 2 weeks of ward-based rehabilitation as an inpatient, our patient was afebrile, symptom-free and mobilising with one crutch. repeat imaging demonstrated marked improvement in the hepatic abscesses. he was discharged home to continue intravenous ceftriaxone and oral metronidazole via the outpatient parenteral antimicrobial programme, with plans to continue his anticoagulant therapy for 3 months. follow-up was arranged through the infectious disease clinic and repeat imaging at a 4-week interval showed resolution of hepatic abscesses, resolution of pleural effusions and airspace opacifications (figure 5), with considerable reduction in intracranial abscesses. currently, there is no universally accepted definition of lemierre's syndrome. one danish epidemiological study defined it as a septic case of f. necrophorum infection (confirmed in blood cultures), with a primary focus in the head and neck (typically of oropharyngeal origin), disseminated to nearby or remote regions. 2 some authors specify that the infection must originate in the throat (thus excluding infections arising from the ears, teeth or mastoid region), while others do not require isolation of f. necrophorum to confirm the disease. 4 the complexity of the disease and the variable clinical presentation makes a concise definition difficult. as such, it is essential that clinicians across the myriad specialties recognise the wide range of signs and symptoms that should raise suspicion of lemierre's disease. while the majority of cases are of oropharyngeal origin, lemierre's syndrome can also arise as a complication of an odontogenic infection, 7 and disseminated f. necrophorum infection has even been described following routine dental cleaning. 8 cases of metastatic spread of f. necrophorum involving the lungs, liver, meninges, endocardium, skin/soft tissue, bone, joints and even the peripancreatic tissues have all been described. 2 4 9 renal and cerebral abscess have also been reported, but are rare. 3 while the majority of cases feature pulmonary involvement, our case is unusual in that our patient presented with signs and symptoms resulting from widespread embolisation across a multitude of different organs. furthermore, brain abscesses are thought to result from retrograde intracranial extension of ijv thrombosis. 3 in our case, ct imaging identified intracranial abscess formation prior to the detection of ijv involvement, suggesting an alternative route of seeding-perhaps via the patent foramen ovale (though allowing for the possibility that ijv involvement was simply not visible on the initial ct). we also acknowledge that the non-occlusive lesion observed in the ijv on repeat ct imaging of the neck could have represented thrombosis secondary to recent catheterisation. recommended treatment typically involves antimicrobial therapy with a beta-lactam agent and metronidazole for 3-6 weeks. 3 where accessible, drainage of abscesses is also advised. 4 though some articles describe respiratory failure requiring ventilation as uncommon, 4 other studies and case reports recommend involvement of the critical care team at an early stage to ensure adequate monitoring and support, with one study reporting intubation in up to 37% of cases. 10 the role for anticoagulation in lemierre's syndrome remains unclear. 11 while anecdotal reports suggest a reduced risk of septic embolic events arising from the ijv thrombosis with anticoagulation, 3 other studies suggest that anticoagulation be reserved for patients with retrograde progression of thrombus, as most do well without. 4 in our case, given the temporal association between the ijv thrombosis and recent insertion of an intravascular catheter device, a 3-month period of anticoagulation was deemed appropriate. there was no evidence of further embolisation or seeding of infection following initiation of anticoagulation in this instance. circumstances surrounding this case-namely the global sars-cov-2 pandemic-were intrinsically linked to the course of events. the irish dental association warned that in many places, emergency care could not be provided during the sars-cov-2 pandemic due to unavailable or unaffordable personal protective equipment. 12 furthermore, the national ► this case highlights the importance of providing medical and dental services during a public health emergency or pandemic; failure to do so may result in hospital admissions with severe illnesses that might otherwise have been treatable in an outpatient setting. ► lemierre's syndrome can give rise to septic emboli involving multiple sites throughout the body, and should be considered in cases of disseminated infection of unknown origin. ► this case demonstrates the importance of considering lemierre's syndrome arising from periodontal infection, and how source control should be considered along with antimicrobial therapy and drainage of accessible collections. ► intracranial involvement should be considered and investigated in lemierre's syndrome, even in the absence of confirmed internal jugular vein thrombosis. restrictions requiring that people stay at home wherever possible may have delayed certain people who might otherwise have sought prompt medical attention. we describe a severe case of lemierre's syndrome, requiring icu admission and intubation, where presentation and initiation of treatment were delayed by the sars-cov-2 pandemic. our case is unusual in having spread from a periodontal infection, involving multiple organs, and featuring intracranial involvement, initially in the absence of radiological evidence of ijv thrombosis. this could represent intracranial seeding of septic emboli via a patent foramen ovale. initiation of anticoagulation did not result in detectable increase in embolic events, and a good clinical response was achieved with antimicrobial therapy, abscess drainage and source control. incidence, risk factors, and outcomes of fusobacterium species bacteremia lemierre's syndrome and other disseminated fusobacterium necrophorum infections in denmark: a prospective epidemiological and clinical survey lemierre's syndrome: a forgotten and re-emerging infection lemierre's syndrome: more than a historical curiosa impact of coronavirus disease 2019 (covid-19) outbreak on st-segment-elevation myocardial infarction care in hong kong the effects of the covid-19/sars-cov-2 pandemic outbreak on otolaryngology activity in italy lemierre's syndrome: a serious complication of an odontogenic infection hepatic abscess caused by fusobacterium necrophorum after a trip to the dentist fusobacterium necrophorum -beyond lemierre's syndrome lemierre's syndrome: a pain in the neck with far-reaching consequences lemierre's syndrome: what are the roles for anticoagulation and long-term antibiotic therapy? dentists in dire need of support, says dental association chief. the irish times. health contributors fh and lo composed the original draft, with fh taking the lead on the literature review, and lo compiling the case report. fh was also involved in the care of the patient during the course of their admission. nm reported on and compiled the images, reviewed the manuscript and provided critical feedback and advice with reference to the manuscript. ro was the overall supervisor of the project. she helped direct the content and structure of the manuscript, with input into the concept. ro provided critical feedback, and was also the consultant in charge of the care of the patient in question. all authors contributed to the editing and finalising of this manuscript. all authors have given final approval to the version herein attached, and agree to be accountable for all aspects of the work.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. key: cord-333227-849bm17h authors: grewal, ekjot; sutarjono, bayu; mohammed, ibbad title: angioedema, ace inhibitor and covid-19 date: 2020-09-09 journal: bmj case rep doi: 10.1136/bcr-2020-237888 sha: doc_id: 333227 cord_uid: 849bm17h sars-cov-2, the virus responsible for covid-19, binds to the ace2 receptors. ace2 is thought to counterbalance ace in the renin-angiotensin system. while presently it is advised that patients should continue to use ace inhibitors or angiotensin receptor blockers, questions still remain as to whether adverse effects are potentiated by the virus. here, we report a case of a 57-year-old man, unknowingly with covid-19, who presented to the emergency department with tongue swelling, shortness of breath and difficulty in speaking following 4 months taking benazepril, an ace inhibitor. finally, we also describe possible pathways that exist for sars-cov-2 to interact with the mechanism behind angioedema. the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) is a novel lineage b betacoronavirus that emerged at the end of 2019. 1 it was identified as the pathogen that caused acute severe respiratory illness colloquially known as covid-19. 2 sars-cov-2 binds with high affinity to human ace2 receptors, 3 possibly leading to its downregulation. 4 ace2 is expressed broadly, including in the heart, kidneys and lungs. 5 ace2-expressing cells are also found in oral tissue, especially in the epithelial cells of the tongue, 6 and it has been reported that sars-cov-2 was detected in resected tissue of the tongue and submandibular gland. 7 animal and human studies have shown that ace inhibitors and angiotensin receptor blockers (arbs) may modulate ace2 expression. 8 therefore, the implications of using these medications in a patient with covid-19 may have previously unexpected consequences. here, we report of a covid-19positive patient who was prescribed an ace inhibitor and presented to the emergency department with angioedema, a potentially life-threatening adverse drug reaction of ace inhibitors. a 57-year-old man with a medical history of hypertension and type 2 diabetes mellitus presented in the emergency department with worsening swelling of the tongue, difficulty in speaking and shortness of breath since the morning. he was given multiple doses of intramuscular epinephrine in the prehospital setting with no change in symptoms. he had no associated pain, itchiness or rash, and he denied fever, nausea, vomiting, chest pain or cough. he reported not having any allergies or eating anything outside of his regular diet. the patient stated he began taking a new blood pressure medication, benazepril, approximately 4 months ago. he had no personal or family history of facial or tongue swelling. on examination, the patient was afebrile and normotensive, with an oxygen saturation of 96% on room air. there was pronounced oedema involving the lingual mucosa and subcutaneous tissues of the perioral area without pain or pruritus. cardiac auscultation revealed tachycardia without any pathological murmurs. auscultation of the lungs revealed decreased breath sounds bilaterally with inspiratory effort, but no wheezing or crepitations. no jugular venous distention or lower limb swelling was appreciated. no urticarial eruption was noted throughout. laboratory tests revealed mild leucocytosis (10.8×10 9 /l) with lymphopenia (800×10 9 /l) and elevated high-sensitivity c-reactive protein (7.80 mg/dl), ferritin (866 ng/ml) and lactate dehydrogenase (1295 iu/l). d-dimer, c3 and c4 levels were not measured. chest x-ray showed bilateral infiltrates in lung bases (figure 1), whereas ct impressions showed multifocal alveolitis in the periphery of the upper lobes bilaterally (not shown). ct imaging of the neck showed oedema along the prevertebral and submucosal tissues of the oropharynx and hypopharynx (figure 2), as well as in the submandibular area surrounding the submandibular glands. a nasopharyngeal swab was anaphylaxis was our initial diagnosis of exclusion. without positive clinical response following epinephrine administration, delay in considering alternative diagnoses may have lead to a fatal outcome. 9 other differential diagnoses chiefly included deep space abscess and hereditary or acquired angioedema. we considered infectious processes such as a lingual abscess, 10 or ludwig's angina, a form of submandibular space infection arising from the odontogenic origin 11 ; however, without fever, pain or specific fluctuant oedema, infectious processes were mostly ruled out. trauma is a common cause of tongue swelling, particularly from epileptic tongue bites, 12 although the absence of personal history meant this was unlikely. neoplasm was also a possibility, most commonly caused by oral squamous cell carcinoma of the tongue, 13 as was lingual thyroid, an abnormal mass of ectopic thyroid tissue normally seen in the base of the tongue from defects in embryogenesis. 14 the rapidity of symptom onset did not correspond to this picture. rarer possibilities included submental haematoma, seen in anticoagulated patients, 15 and melkersson-rosenthal syndrome, which is normally accompanied by recurrent congenital facial nerve palsy. 16 alternatively, other rare causes are tuberculosis of the tongue, which manifests in immunocompromised individuals, 17 and tertiary syphilis, which has been shown to invade the tongue in patients with chronic infection. 18 angioedema is the non-pruritic swelling of the deeper layers of the skin or mucosa, which can be fatal when it obstructs the airway. 19 ultimately, in the absence of family history or repeated occurrence of angioedema, hereditary angioedema 20 was less likely. ace inhibitor-associated angioedema was our primary diagnosis due to the recent use of ace inhibitors in the last few months. however, during the height of the initial surge in new york city, we questioned whether sars-cov-2 could cause or at least potentiate angioedema. other workup showed bilateral pulmonary infiltrates and elevated inflammatory markers with lymphopenia consistent with covid-19 infection. the decision to administer tranexamic acid in our patient with ace inhibitor-induced angioedema was based on the evidence shown by a retrospective study in france. 21 fresh frozen plasma, which has been shown to have success in treating ace inhibitorinduced angioedema, 22 was prepared for the alternative measure. in the emergency department, the patient's clinical presentation improved over 3 hours once tranexamic acid was given. although the patient was able to talk, his voice was hoarse, and the decision was then made to admit the patient for airway monitoring. intravenous diphenhydramine and famotidine were given, and benazepril was withheld. the angioedema resolved within 24 hours without further oropharyngeal swelling. oxygen saturation was above 95% on room air despite suspicion for covid-19. the patient was given oral diphenhydramine and famotidine to continue at home, whereas amlodipine was prescribed for hypertension in place of ace inhibitors. he was also advised to follow-up with his primary care provider to modify his blood pressure medication. soon after discharge, the patient's pcr result for covid-19 returned positive. currently, there is one other reported case of angioedema without urticaria in an ace inhibitor user with covid-19. 23 the presentation of this case report is similar to our own: nonpitting oedema of the lower face in the absence of pruritus, leucocytosis with relative lymphopenia, elevated inflammatory markers and resolution of symptoms within 48 hours, although the marked difference is the chronic use of ace inhibitor, whereas our patient began his medication 4 months prior to admission. the rapid improvement following tranexamic acid treatment in the emergency department validated our initial assessment of ace inhibitor-induced angioedema. the development of angioedema is initiated by kallikrein, cleaving the active nonapeptide bradykinin from kininogen. bradykinin generates nitric oxide and prostaglandins, which leads to vasodilatation and increased vascular permeability, particularly the postcapillary venules. bradykinin is primarily degraded by ace, neutral endopeptidase, aminopeptidase p, dipeptidyl peptidase iv and kininase i. 24 however, approximately 11% is converted into des-arg 9 -bradykinin, which is cleaved by ace2. ace2 converts angiotensin ii to its metabolite angiotensin-(1-7), which counterbalances ace in the renin-angiotensin system, 25 opposing its effects of vasoconstriction, sodium retention and fibrosis. 26 therefore, the theoretical downregulation of ace2 by sars-cov-2 would lead to the elevated angiotensin ii, creating an environment for a heightened level of bradykinin leading to angioedema. the clinical presentation of patients with covid-19 and ace2 modulation are strikingly similar. for example, endotoxin inhalation in a mouse model causes a drastic reduction in pulmonary ace2 activity, and the extended longevity of des-arg 9bradykinin exacerbates lung inflammation, 27 with a presentation similar to acute respiratory distress syndrome (ards) as seen in patients with covid-19. an impairment of cytokine degradation, evident by an increase in the level of c-reactive protein, has been implicated as being the primary mechanism of angioedema under the use of ace inhibitor drugs, 28 which greatly resembles the dramatic release of proinflammatory cytokines caused findings that shed new light on the possible pathogenesis of a disease or an adverse effect by sars-cov-2 infection. 29 c-reactive protein also stimulates interleukin-6. 30 both c-reactive protein and interleukin-6 have been shown to be above the normal range in most patients with covid-19 31 and c-reactive protein was shown to be elevated in both cases of angioedema in patients with covid-19. patients with covid-19 also have markedly elevated plasma angiotensin ii level that is linearly associated with viral load and lung injury. 32 interestingly enough, the characteristic side effect of ace inhibitor therapy, a dry cough, closely resembles the coughing in patients with covid-19 as well. it is difficult to elucidate whether the sars-cov-2 caused angioedema in both patients. it is possible that sars-cov-2 may be the trigger for angioedema when combined with the use of ace inhibitors under a 'two-hit' mechanism. it has been documented that the addition of another medication can cause angioedema in individuals previously stable under ace inhibitors. a common trigger is non-steroidalanti-inflammatory drugs, which may account for close to 50% of all ace inhibitor-related angioedema. 33 other medications, such as dipeptidyl peptidase iv inhibitors and mtor inhibitors, are also associated with an increased incidence of angioedema with chronic use of ace inhibitors. 34 35 with the use of omapatrilat, which concomitantly inhibits ace as well as neutral endopeptidase, angioedema was observed at a rate threefold higher in comparison with enalapril during the octave trial. 36 neutral endopeptidase is the inactivating enzyme for apelin. 37 apelin, meanwhile, interacts with ace2. apelin is also normally cleaved and rendered inactivated by kallikrein. 38 thus, these are examples of multiple pathways that may be prone to modification by sars-cov-2. the existence of potential interactions creates more questions than answers. future research should focus on acquiring levels of bradykinin and des-arg 9 -bradykinin in order to determine if either of these compounds are influenced by sars-cov-2 infection. icatibant, a competitive bradykinin b2 receptor antagonist, has been used for therapeutic management of ace inhibitorrelated angioedema with early use considered in severe cases. 39 c1-esterase inhibitor concentration (c1-inh) should also be investigated for its potential mechanism that may be vulnerable to sars-cov-2 infection, as its deficiency is known to cause the hereditary form of angioedema, where increasing its concentration may prove therapeutic. 40 due to the emergent nature of ace inhibitor-induced angioedema, we recommend a broader laboratory investigation as well as an exploration of treatment utilising icatibant or c1-inh concentrates. although it is unknown whether sars-cov-2 may cause angioedema, many avenues exist for possible interaction. in accordance with current consensus, [40] [41] [42] we support the continuation of ace inhibitor and arb therapy during the pandemic and if infected with sars-cov-2. however, increased vigilance should be taken in patients who have sustained use of ace inhibitors with elevated risk factors for contracting covid-19, and we urge more research on the matter. ► ace inhibitor and angiotensinreceptor blocker therapy should be continued during the covid-19 pandemic and if infected with sars-cov-2. ► tranexamic acid and fresh frozen plasma are effective treatments for ace inhibitor-induced episodes of angioedema during an urgent setting. ► common causes of tongue swelling include anaphylaxis, angioedema, infection, trauma, neoplasm and ectopic thyroid tissue. ► sars-cov-2 has a high affinity to ace2, which counterbalances ace in the renin-angiotensin system. ► while bradykinin, which is thought to cause angioedema, is degraded by ace, a portion is metabolised to des-arg 9bradykinin, which is then degraded by ace2. clinical features of patients infected with 2019 novel coronavirus in wuhan, china joint mission report of the who-china joint mission on coronavirus disease 2019 (covid-19). world health organization functional assessment of cell entry and receptor usage for sars-cov-2 and other lineage b betacoronaviruses sars-cov-2 downregulation of ace2 and pleiotropic effects of aceis/ arbs tissue distribution of ace2 protein, the functional receptor for sars coronavirus. a first step in understanding sars pathogenesis high expression of ace2 receptor of 2019-ncov on the epithelial cells of oral mucosa sars-cov-2 detection in formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma impaired breakdown of bradykinin and its metabolites as a possible cause for pulmonary edema in covid-19 infection caution in diagnosing angioedema as anaphylaxis challenges in the diagnosis of a posterior lingual abscess, a potential lethal disorder: a case report and review of the literature fatal ludwig's angina: cases of lethal spread of odontogenic infection the diagnostic value of oral lacerations and incontinence during convulsive "seizures clinicopathologic predictors of survival in buccal squamous cell carcinoma ectopic thyroid tissue: anatomical, clinical, and surgical implications of a rare entity spontaneous submental hematoma, a pseudo-ludwig's phenomenon in 101-year-old patient: case report and literature review restoration of facial lymphatic drainage in the course of disease tuberculosis of the tongue in a patient with rheumatoid arthritis treated with methotrexate and adalimumab an unusual case of tertiary syphilis behaving like tongue squamous cell carcinoma angioedema deaths in the united states hereditary angioedema intérêt de l'acide tranexamique en traitement d'urgence de première intention des crises d'angioedème bradykinique sous iec [tranexamic acid as first-line emergency treatment for episodes of bradykinin-mediated angioedema fresh frozen plasma in the treatment of ace inhibitor-induced angioedema angioedema in covid-19 bradykinin and the pathophysiology of angioedema ace2: from vasopeptidase to sars virus receptor counterregulatory actions of angiotensin-(1-7) attenuation of pulmonary ace2 activity impairs inactivation of des-arg 9 bradykinin/bkb1r axis and facilitates lps-induced neutrophil infiltration increased c-reactive protein in ace-inhibitorinduced angioedema covid-19: consider cytokine storm syndromes and immunosuppression differential acute-phase response of rat kininogen genes involves type i and type ii interleukin-6 response elements epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study clinical and biochemical indexes from 2019-ncov infected patients linked to viral loads and lung injury recurrent severe angioedema associated with imidapril and diclofenac dipeptidyl peptidase iv in angiotensin-converting enzyme inhibitor associated angioedema increased incidence of angioedema with ace inhibitors in combination with mtor inhibitors in kidney transplant recipients omapatrilat and enalapril in patients with hypertension: the omapatrilat cardiovascular treatment vs. enalapril (octave) trial angiotensin-converting enzyme 2 metabolizes and partially inactivates pyr-apelin-13 and apelin-17: physiological effects in the cardiovascular system plasma kallikrein cleaves and inactivates apelin-17: palmitoyl-and peg-extended apelin-17 analogs as metabolically stable blood pressure-lowering agents a randomized trial of icatibant in ace-inhibitorinduced angioedema angiotensin-converting enzyme inhibitor-associated angioedema treated with c1-esterase inhibitor: a case report and review of the literature latest data support continued use of ace inhibitors and arb medicines during covid-19 pandemic national institutes of health. considerations for certain concomitant medications in patients with covid-19. nih: covid-19 treatment guidelines key: cord-311232-hhfdqhx1 authors: yang, yunfei; qidwai, umair; burton, benjamin j l; canepa, carlo title: bilateral, vertical supranuclear gaze palsy following unilateral midbrain infarct date: 2020-11-04 journal: bmj case rep doi: 10.1136/bcr-2020-238422 sha: doc_id: 311232 cord_uid: hhfdqhx1 a 60-year-old man recently admitted for bipedal oedema, endocarditis and a persistently positive covid-19 swab with a history of anticoagulation on rivaroxaban for atrial fibrillation, transitional cell carcinoma, cerebral amyloid angiopathy, diabetes and hypertension presented with sudden onset diplopia and vertical gaze palsy. vestibulo-ocular reflex was preserved. simultaneously, he developed a scotoma and sudden visual loss, and was found to have a right branch retinal artery occlusion. mri head demonstrated a unilateral midbrain infarct. this case demonstrates a rare unilateral cause of bilateral supranuclear palsy which spares the posterior commisure. the case also raises a question about the contribution of covid-19 to the procoagulant status of the patient which already includes atrial fibrillation and endocarditis, and presents a complex treatment dilemma regarding anticoagulation. cerebrovascular accidents (cva) comprise the second leading cause of death worldwide and the third leading cause of disability, with approximately 80% of all stroke being ischaemic in origin, 10% due to haemorrhage, 5% due to subarachnoid haemorrhage and the remainder due to other causes of stroke. 1 it can manifest in a variety of presentations depending on location of the defect. vertical gaze palsy describes a conjugate bilateral limitation of upgaze and/or downgaze. it primarily affects the saccadic eye movement pathway but can also affect smooth pursuit or optokinetic movements, and can be considered as a supranuclear, nuclear or infranuclear problem of origin. three key anatomical centres are most important in the vertical gaze centre: (1) the rostral interstitial nucleus of the medial longitudinal fasciulus (rimlf) in the midbrain for control of vertical and torsional saccades, (2) the interstitial nucleus of cajal (inc), the neural integrator of vertical and torsional gaze and (3) and the posterior commisure (pc) in the dorsal aspect of the superior end of the cerebral aqueduct. vertical gaze palsies are recognised in a variety of syndromes not limited to parkinsonismplus syndromes (progressive supranuclear palsy and corticobasilar syndrome), storage disorders (niemann-pick type c) or parinaud's syndrome, but should also be recognised as a result of autoimmune, malignant, drug-induced and traumatic causes. vascular causes of supranuclear gaze palsy typically localise to the midbrain or the thalamus. this case combines an interesting unilateral lesion causing bilateral symptoms, an awareness of the multifactorial aetiology of strokes and a lesson in managing the risk-benefit of anticoagulation in the context of both ischaemic and haemorrhagic risk factors. a 60-year-old male patient with a background of hypertension, diabetes, chronic obstructive pulmonary disease and atrial fibrillation, for which he was taking rivaroxaban, and a diagnosis of transitional cell carcinoma of the bladder 5 years prior (undergoing chemotherapy and cysto-prostatectomy), presented with rapidly-progressive bilateral ankle oedema (progressing to upper legs in 2 days), back pain, reduced appetite and intermittent fever. x-ray of the lungs were clear, but an echocardiogram detected mitral vegetations and subsequent blood cultures grew streptococcus sanguinis, a common oral commensal bacterial. he had no history of dental work. roughly 10 days after admission, he developed a new dry cough and tested positive for sars-cov2 rna, improving with oxygen support. one week later, he developed a non-st elevated myocardial infarction. during the last phase of isolation for covid-19, he developed sudden onset of vertical diplopia, lightheadedness, vertigo and unsteady gait. on examination, there was restricted bilateral upward gaze movements with mild limitation for abduction in the right eye and inability for bilateral convergence, without limitation for downward gaze on either side (video 1). the vertical vestibulo-ocular reflex (vor) was preserved (video 2). pupils were equal and reactive to light directly and indirectly. diffusion-weighted mri (figure 1) showed an acute, small left-sided paramedian midbrain infarct without thalamic involvement, and t2* (echo gradient) imaging showed a couple of small, chronic microhaemorrhages in the parietal and temporal lobes, secondary to long-standing asymptomatic amyloid angiopathy. he had no history of transient neurological attacks, seizures, dysaesthesia, hemiataxia, diplopia or hemiparesis. almost simultaneously, he also developed a sudden onset of black patch obstructing his central and superior field of view and could only manage to see hand movement from the right eye, which was suggestive of a branch/ hemi-retinal artery occlusion and later confirmed using optical coherence tomography. also, single embolus in the inferior branch of the retinal artery was clearly visible (figure 2), confirming the occlusion of branch or hemi-retinal artery. the patient never complained of either headache, temperature changes or recent history of weight loss. c reactive protein and erythrocyte sedimentation rate were mildly elevated; however, there was no evidence of temporal arteritis. autoantibody testing, in the form of anti-nuclear antibodies, antineutrophil cytoplasmic antibodies, membrane p3 and c4/d3 were all negative and thus incompatible with an autoimmune cause. it was felt that these inflammatory reactants were more likely linked to active covid-19 infection and bacterial endocarditis. coagulation, full blood count and lipid profile were all in normal range. d-dimer was 348. he was diagnosed with bilateral supranuclear gaze palsy secondary to a left paramedian midbrain infarct and a right branch retinal artery occlusion. treatment with high-dose aspirin (300 mg/day) was given for 1 week, followed by apixaban for long-term secondary prevention of strokes. he also continued antibiotic treatment for endocarditis, with gradual improvement. a repeat sars-cov2 rna test was positive after 2 weeks of the initial result; however, the patient was asymptomatic at the time. ► ct and mri of the brain. ► echocardiogram. ► blood investigations including antibody testing for sars-cov2. ► ct carotid arteries. ► a 24-hour tape was not requested as the patient was already known to have atrial fibrillation. the acute onset of vertical diplopia was suggestive of an ischaemic event; however, the cause for the acute onset of bilateral vertical gaze palsy was not obvious. a normal vor confirmed the supranuclear nature of the condition. ischaemic events have been reported to cause bilateral supranuclear vertical gaze palsy, but they are not common. other differential diagnoses considered were metastasis or a primary brain tumour, causing downward compression of the midbrain (and on the upward gaze centres). an mri confirmed a midbrain infarction. we considered various causes for infarction, as for the embolic branch retinal artery occlusion, including atrial fibrillation, bacterial endocarditis, previous neoplastic disorder and a persistently positive sars-cov2, which appears to have a procoagulant effect. the patient was treated with aspirin 300 mg initially, then changed to apixaban for secondary prevention of cardioembolic events. he was also treated with antibiotics for bacterial endocarditis. the patient has continued to make a good recovery in the ward, with gradual improvement of eye movements and is due for follow-up by the stroke team 6 weeks after initial presentation, by neurology 2 months later and cardiology in 6 weeks following discharge. he has continued to make good functional recovery. premotor control of vertical gaze depends on the integrity of the pc, inc and the rimlf. neurons for upward saccades innervate both ipsilateral and contralateral oculomotor and trochlear nerve nuclei whereas those that mediate downward saccades innervate the oculomotor and trochlear nerve nuclei ipsilaterally only. the rimlf and inc are thought to work together to generate ipsilateral torsional eye movements 2 and the pc is involved in vertical gaze as well as pupillary reflexes. supranuclear pathways for vertical saccades travel from both frontal eye fields to innervate the rimlf on each side. vertical saccades require simultaneous activation of both frontal eye fields. from both a clinical and radiological point of view, the patient had involvement of the rimlf and inc, but neither of the pc nor of the nucleus of edinger-westphal. the supranuclear nature of the palsy was confirmed by a preserved vertical vor. there was no evidence of pupillary dysfunction (no fixed and dilated pupil due to parasympathetic damage), ruling out involvement of the edinger-westphal nucleus. the left, unilateral paramedian ischaemic lesion damaged the pathways involved in vertical gaze before they decussate (figure 3), resulting in a bilateral supranuclear gaze palsy. as seen in figures 1 and 3, the infarction does not involve the pc. in most cases, isolated dysfunction of vertical eye movements localises to a midbrain lesion affecting the rimlf, inc, pc or periaqueductal grey matter. unilateral infarction precipitating bilateral vertical gaze palsy are rare and earliest case reports focused on thalamic involvement, with the earliest case 3 described as that of a patient with midbrain and thalamic involvement. further cases reported paramedian thalamic infarction without midbrain involvement, usually secondary to an artery percheron 4 (a variant branch of posterior cerebral artery trunk providing bilateral input to the paramedian thalami and rostral midbrain) infarct resulting in bilateral paramedian thalami infarct, those that presented with a coexisting midbrain lesion. 5 buttner-ennever et al 6 reported a case of vertical gaze palsy secondary to rimlf involvement. bogousslavsky et al 7 described a histologically confirmed case of vertical gaze palsy due to selective unilateral infarction of rimlf. vertical gaze palsies without pc involvement are even rarer. a unilateral rimlf and inc lesion but sparing pc tract causing complete upward case report but partial downward vertical gaze palsy was first reported in 1988. 8 further reports have been reported in japan, 9 turkey 10 and belgium, 11 and iatrogenically secondary to cerebral digital subtraction angiography; 12 in all the cases, there was inc and rimlf involvement with sparing of the pc, with no evidence of pupillary dysfunction. only in the belgian iatrogenic case was there both upward and downward gaze palsy, but vor was also impaired unlike in our case. evidence for vertical one-and-a-half syndrome was sought, but no evidence was found. this phenomenon was first described in 1983 following a thalamomesencephalic infarction 13 and again in 2012. 14 the patient had vertical gaze disorder associated with ipsilateral downward gaze palsy and only contralateral upward gaze palsy. this is an important differential diagnosis to consider in any patient with an acute onset of bilateral upward gaze palsy. in such cases, apart from the upward gaze palsy, there is also ipsilateral downward gaze palsy. as seen in video 1, the patient did not have downward gaze palsy. the aetiology and long-term management of the ischaemic stroke in this case also warrants further discussion. the patient not only had a history of small vessel disease in the context of cerebral amyloid angiopathy (caa) but also had a history of atrial fibrillation controlled with rivaroxaban as well as s. sanguinis endocarditis. acute ischaemic stroke is the most common neurological manifestation of infective endocarditis, reported in up to 40% of cases and classically affecting the middle cerebral artery 15 and the vegetation affecting mitral valve. cerebral microbleeds are also a common complication of infective endocarditis and there is no evidence to support the use of anticoagulants or antiplatelet drugs in acute stroke due to infective endocarditis. 16 this patient also had caa, which is one of two cerebral small vessel diseases that cause the majority of non-traumatic haemorrhagic stroke, the risk-benefit analysis of anticoagulation is more complicated. caa results from an age-related deposition of beta-amyloid protein in the leptomeningeal and cortical cerebral vessels. 17 a major prospective cohort study of 1490 participants, the clinical relevance of microbleeds in stroke trial (cromis-2), 18 compared the rate of symptomatic intracranial haemorrhage in patients with electrocardiogram-confirmed non-valvular atrial fibrillation who presented with transient ischaemic attack or ischaemic stroke and who were candidates for direct oral anticoagulants (doac). the main findings were that those who had a symptomatic intracranial haemorrhage had a higher prevalence of diabetes, vitamin k antagonist use (as opposed to doac) or cerebral microvascular bleeding (which confirmed a three times higher hazard ratio). therefore, had the patient solely had caa, anticoagulation would be avoided due to the risk of intracranial bleeding. however, acutely, the patient also presented with covid-19. covid-19 is caused by the sars-cov-2, the seventh known variant of coronavirus that affects humans. cellular entry is primarily through ace-2 receptors. the exact mechanism of central nervous system entry has not been elucidated but both haematogenous spread from systemic to cerebral circulation and dissemination though cribriform plate and olfactory bulb are considered. a recent systematic review reported a prevalence of 34.6% of neurological symptoms across 214 patients, 19 with those with more severe systemic presentations more likely to have neurological symptoms. several case reports in the literature have also reported an association of covid-19 and stroke but the overall prevalence reported is rare. the earliest description was in a single centre retrospective analysis in china 20 which reported a stroke prevalence of 5% among those hospitalised at a median of 12 days from initial covid-19 diagnosis and a mean age of 71.6 years and classically with multiple cardiovascular risk factors. a much higher prevalence was found among cohort of 725 patients from italy, with a reported prevalence of 31% of ischaemic stroke. 21 the link with systemic risk factors was reinforced in a case series involving covid-19 patients with large vessel stroke under the age of 50 years, with three of them having vascular risk factors (diabetes, dyslipidaemia and hypertension). 22 'sepsis-driven coagulopathy', and the hypercoagulability and vascular endothelial dysfunction it confers is thought to be the main mechanism driving ischaemic stroke. however, other factors include the presence of lupus anticoagulant 23 and the high d-dimers during the course of the disease. 24 cases of ischaemic strokes have occurred even with previous long-term anticoagulation 25 and thromboprophylaxis is advised in all patients with covid-19. ischaemic stroke management in the long term usually involves the use of long-term anticoagulation. in this patient, who has atrial fibrillation, anticoagulation also becomes more important given the fivefold increased risk in these patients for ischaemic stroke, contributing to 30% of ischaemic strokes. 26 this patient had strong cardiac risk factors (atrial fibrillation and established infective endocarditis) but could potentially have a long-standing procoagulant disposition following his persistently positive covid-19 status. such complex situations warrant multidisciplinary input from neurologists, cardiologists and neuroradiologists in assessing risk-benefit, 27 as although direct oral anticoagulants have been reported to carry a lower risk of intracranial haemorrhage, other options, such as left atrial appendage, may avoid long-term anticoagulation. for this situation, a switch to apixaban after initial treatment with aspirin 300 mg was preferred because it presents the least risk for secondary bleeding in a patient with chronic caa microhaemorrhages, while reducing the risk of cardioembolism due to atrial fibrillation. 28 29 learning points ► acute onset of supranuclear gaze palsy may likely be a presenting sign of a midbrain infarction. in such cases, an mri is required, as a ct will not suffice to detect a lesion. ► posterior commissure involvement, as described in parinaud's syndrome, is not always necessary to cause vertical gaze palsy. ► unilateral midbrain infarction can lead to bilateral supranuclear palsy, vertical one-and-a-half syndrome or halfand-a-half syndrome. ► the apparent pro-coagulant effect of covid-19 is not negligible and must be considered a vascular risk factor. contributors yy and cc composed the first draft of the manuscript. bjlb and uq reviewed and edited the manuscript and reviewed the patient in the clinic for disc imaging and follow-up for the retinal artery occlusion. cc conceived the project, was involved in the direct patient contact, history-taking and consent for the project. cc created figure 3 as an original image. all authors reviewed and gave final approval of the version to be published. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer-reviewed. this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, the global burden of cerebrovascular disease graefe's arch clin exp ophthalmol paramedian thalamic and midbrain infarct: clinical and neuropathological study vertical gaze palsy due to acute bilateral thalamic infarct without midbrain ischemia unilateral thalamic infarction and vertical gaze palsy: cause or coincidence? vertical glaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus vertical gaze palsy and selective unilateral infarction of the rostral interstitial nucleus of the medial longitudinal fasciculus (rimlf) palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations vertical gaze palsy caused by selective unilateral rostral midbrain infarction unilateral midbrain infarction causing upward and downward gaze palsy conjugate downward and upward vertical gaze palsy due to unilateral rostral midbrain infarction bilateral vertical gaze palsy after cerebral digital subtraction angiography due to unilateral midbrain infarction upgaze palsy and monocular paresis of downward gaze from ipsilateral thalamo-mesencephalic infarction: a vertical "one-and-a-half" syndrome vertical 'half-and-a-half' syndrome: figure 1 acute ischemic stroke treatment in infective endocarditis: systematic review when the heart rules the head: ischaemic stroke and intracerebral haemorrhage complicating infective endocarditis cerebral amyloid angiopathy: emerging concepts cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (cromis-2): a multicentre observational cohort study neurologic manifestations of hospitalized patients with coronavirus disease 2019 in wuhan, china acute cerebrovascular disease following covid-19: a single center, retrospective, observational study imaging in neurological disease of hospitalized covid-19 patients: an italian multicenter retrospective observational study large-vessel stroke as a presenting feature of covid-19 in the young coagulopathy and antiphospholipid antibodies in patients with covid-19 high risk of thrombosis in patients with severe sars-cov-2 infection: a multicenter prospective cohort study acute ophthalmic artery occlusion in a covid-19 patient on apixaban cerebral amyloid angiopathy: diagnosis, clinical implications, and management strategies in atrial fibrillation the clinical dilemma of anticoagulation use in patients with cerebral amyloid angiopathy and atrial fibrillation risks and benefits of direct oral anticoagulants versus warfarin in a real world setting: cohort study in primary care elderly bleeding risk of direct oral anticoagulants in nonvalvular atrial fibrillation: a systematic review and meta-analysis of cohort studies non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. yunfei yang http:// orcid. org/ 0000-0002-7130-9801 key: cord-297693-lqyc49t6 authors: samec, matthew j; khawaja, ali; patel, ashokakumar m; dugani, sagar b title: 80-year-old man with dyspnoea and bilateral groundglass infiltrates: an elusive case of covid-19 date: 2020-05-27 journal: bmj case rep doi: 10.1136/bcr-2020-236069 sha: doc_id: 297693 cord_uid: lqyc49t6 covid-19 is a novel viral infection caused by severe acute respiratory syndrome-coronavirus-2 virus, first identified in wuhan, china in december 2019. covid-19 has spread rapidly and is now considered a global pandemic. we present a case of a patient with minimal respiratory symptoms but prominent bilateral groundglass opacities in a ‘crazy paving’ pattern on chest ct imaging and a negative initial infectious workup. however, given persistent dyspnoea and labs suggestive of covid-19 infection, the patient remained hospitalised for further monitoring. forty-eight hours after initial testing, the pcr test was repeated and returned positive for covid-19. this case illustrates the importance of clinical vigilance to retest patients for covid-19, particularly in the absence of another compelling aetiology. as covid-19 testing improves to rapidly generate results, selective retesting of patients may uncover additional covid-19 cases and strengthen measures to minimise the spread of covid-19. covid-19 is a novel viral infection caused by severe acute respiratory syndrome-coronavirus-2 virus, first identified in wuhan, china in december 2019. covid-19 has spread rapidly and is now considered a global pandemic. we present a case of a patient with minimal respiratory symptoms but prominent bilateral groundglass opacities in a 'crazy paving' pattern on chest ct imaging and a negative initial infectious workup. however, given persistent dyspnoea and labs suggestive of covid-19 infection, the patient remained hospitalised for further monitoring. forty-eight hours after initial testing, the pcr test was repeated and returned positive for covid-19. this case illustrates the importance of clinical vigilance to retest patients for covid-19, particularly in the absence of another compelling aetiology. as covid-19 testing improves to rapidly generate results, selective retesting of patients may uncover additional covid-19 cases and strengthen measures to minimise the spread of covid-19. in december 2019, a novel virus, severe acute respiratory syndrome-coronavirus-2 (sars-cov-2), was identified in wuhan, china. initially thought to be comparable to influenza, our understanding of covid-19, caused by sars-cov-2 is evolving daily. it has caused a global disturbance due to its high transmission rate. who officially labelled covid-19 as a pandemic on 11 march 2020, with the disease having spread to >190 countries. as of 07 april 2020, there were more than 1 400 000 confirmed cases with over 80 000 deaths. 1 sars-cov-2 is a non-segmented, positive sense rna virus that was first isolated from people who had visited the huanan seafood market in wuhan, china. 2 coronaviruses are naturally found in bats, which were postulated to be the primary reservoir for zoonotic transmission to humans in prior cases of coronavirus infection. 3 4 this is, expectedly also true for sars-cov-2 as genetic studies have identified more than 96% similarity in the whole genome sequencing of sars-cov-2 and a bat sars-related coronavirus (ratg13) in china. 5 in addition, pangolins have also been identified as potential reservoirs of coronavirus. 6 sars-cov-2 binds the ace2 receptor located on type ii alveolar cells and intestinal epithelia. this is the same receptor used by the severe acute respiratory syndrome coronavirus-1 (sars-cov-1), hence the technical name for covid-19 being sars-cov-2. 7 8 the clinical presentation for sars-cov-2 varies from being asymptomatic to developing mild upper respiratory tract infection to severe pneumonia resulting in acute respiratory distress syndrome. 9 this has posed challenges in halting the transmission via droplets due to asymptomatic carriers as well as identifying patients who can potentially decompensate later in the clinical course. as we learn more about covid-19, we need to adapt and identify the means of early diagnosis, its management and most importantly, its prevention. we present a case of an 80-ear-old man who posed a diagnostic dilemma and the thoughts behind our decision-making process which could be useful to other clinicians managing patients with covid-19. an 80-year-old man presented to the emergency department with dyspnoea and nausea. his comorbidities included atrial fibrillation requiring cardioversion currently receiving anticoagulation with apixaban, non-ischaemic cardiomyopathy causing biventricular heart failure and left bundle branch block requiring cardiac resynchronisation therapy-defibrillation placement with most recent ejection fraction of 54%, hyperlipidaemia, gastrooesophageal reflux disease and pseudogout. he was a remote smoker having quit more than 50 years ago, worked as a financial planner and denied any concerning exposures. his dyspnoea was primarily with exertion and had gradually progressed over the preceding 6-8 weeks. his primary residence was in tennessee but he travelled extensively for work, most recently to new york, almost 4 weeks prior to his presentation. he did not have any known sick contacts. in the week prior to presentation, the patient had an acute change in exertional dyspnoea that resulted in difficulty climbing a flight of stairs. this acute change correlated with new onset nausea and loss of appetite. notably, he did not have fevers, cough, sputum production, haemoptysis, chest pain, orthopnoea, lower extremity oedema or weight gain. he initially sought recommendations from his local primary care provider a week prior to presentation who temporarily increased the patient's dose of furosemide. however, this did not alleviate his dyspnoea. in the emergency department, he was afebrile and normotensive with mild tachypnoea and oxygen saturation of 92% on room air. on examination, he new disease figure 1 chest x-ray with bilateral patchy airspace opacities (left), ct chest with bilateral groundglass opacities and crazy-paving pattern. was well appearing, had bibasilar rales with a systolic murmur likely from known tricuspid regurgitation, but without significant jugular venous distension or lower extremity oedema. the remainder of his physical examination was unremarkable. laboratory workup revealed normocytic anaemia with haemoglobin 119 g/l, normal white cell count of 7.5×10 9 /l with reduced absolute lymphocyte count of 0.76×10 9 /l, n-terminal pro brain natriuretic peptide (nt-pro bnp) 1722 pg/ml (normal 5-128 pg/ml), d-dimer 1392 ng/ml (normal ≤500 ng/ml), c-reactive protein (crp) 82.6 mg/dl (normal ≤8 mg/dl), high sensitive troponin t 26 ng/l (normal ≤15 ng/l) without significant change after 2 hours, aspartate aminotransferase 61 u/l (normal 8-48 u/l) with otherwise unremarkable liver function tests and a normal renal function panel. a 12-lead ecg showed a paced rhythm without significant changes from prior readings. chest radiograph revealed new patchy airspace opacities bilaterally. due to an elevated d-dimer and progressive dyspnoea, a chest ct scan with pulmonary angiogram was obtained. ct chest with pulmonary angiogram was negative for pulmonary embolism but demonstrated diffuse bilateral patchy groundglass opacities predominantly in the mid to lower lung zones, which were consistent with crazy paving pattern (figure 1). these findings were new compared with a scan obtained 12 months prior, which showed an unremarkable pulmonary parenchyma. he was admitted to the inpatient medicine service for further workup under modified contact and droplet isolation (use of gown, gloves, surgical mask and eye shield). influenza and respiratory syncytial virus pcr were negative. due to the covid-19 pandemic, his travel history and reports of community transmission within the usa, a nasopharyngeal swab for sars-cov-2 pcr was obtained, which returned negative. the pulmonary medicine team was consulted for consideration of bronchoscopy for further diagnostic workup. due to high suspicion of infection, haemodynamic stability and immunocompetent status, testing with an extended respiratory pathogen panel and repeat sars-cov-2 pcr was recommended. both tests were negative 24 hours after the initial sars-cov-2 pcr. the case was reviewed with the institutional infection prevention and control team who recommended repeating sars-cov-2 pcr 48 hours from the initial test. this was subsequently obtained and was positive, consistent with covid-19 infection. importantly, due to high clinical suspicion, modified contract and droplet precautions were maintained while the sars-cov-2 pcr tests were pending. the differential diagnosis of his clinical presentation was broad and included viral or atypical infection including pneumocystis pneumonia, inflammatory/interstitial lung disease such as eosinophilic pneumonia, non-specific interstitial pneumonitis or hypersensitivity pneumonitis and heart failure exacerbation. heart failure exacerbation was less likely due to a stable echocardiogram, normal cardiac device interrogation a week prior to presentation, stable weight and absence of volume overload on examination or imaging. the patient was subsequently transferred to a dedicated medicine service caring for patients positive for covid-19. due to reports of sudden acute decompensation in older patients with covid-19, 10 he was observed in the hospital for a longer duration despite being haemodynamically stable. his inflammatory markers down-trended (table 1) which correlated with symptomatic improvement and he was discharged in stable condition after a total of 8 days of hospitalisation. this case illustrates the importance of clinical suspicion and supplemental diagnostics including ct chest imaging and laboratory data to diagnose covid-19. the primary symptoms in patients hospitalised with covid-19 infection are fever (88.7%), cough (67.8%), fatigue (38.1%), dyspnoea (18.7%), myalgia (14.9%) and chills (11.5%). nausea or vomiting (5.0%) and diarrhoea (3.8%) were less common. common radiological findings included ground-glass opacities (56.4%) and bilateral patchy shadowing (51.8%). no radiological or ct findings were found in 17.9% of patients with non-severe disease and in 2.9% with severe disease. on admission, lymphocytopenia (83.2%), thrombocytopenia (36.2%) and leucopenia (33.7%) were noted. elevations in serum crp, d-dimer, creatine kinase, alanine aminotransferase and aspartate aminotransferase were reported in some cases. 11 a recent study in china retrospectively reviewed the initial chest ct of patients with covid-19 and found ground-glass opacity (61.3%) ground-glass opacity with consolidation (35.5%), crazy-paving pattern (25.8%), rounded opacities (25.8%) and air bronchograms (22.6%). 12 'crazy paving' is a non-specific chest ct finding produced by the amplified density of lung parenchyma that manifests as a ground glass appearance superimposed on reticular thickening of the inter and intralobular septae. 13 this can be seen in sarcoidosis, drug induced pneumonitis, pneumocystis jirovecii pneumonia, pulmonary proteinosis, interstitial lung disease, pulmonary adenocarcinoma, pulmonary haemorrhage, cryptogenic organising pneumonia and bacterial pneumonia. 13 to provide care for patients with 'crazy paving' on chest ct, a thorough investigation into the different causes should be undertaken but covid-19 should remain high on the differential due to its increasing prevalence. nasopharyngeal swabs remain the primary confirmatory test for covid-19. as suggested by the us centers for disease control and prevention, negative results should not be the sole determinant to rule out covid-19 infection. the optimum specimen type and peak viral levels have not been determined, and to detect the virus, multiple specimens at different time points may be required. false negatives may also occur if a specimen is improperly collected or processed or if an inadequate number of organisms are present. ultimately, the positive and negative predictive values of the test are dependent on prevalence of the disease. 14 there have been three published case reports of initially negative covid-19 pcr tests in patients subsequently new disease determined to have covid-19 infection. 15 16 other sites of collection were recently tested in confirmed cases of covid-19 with bronchoalveolar lavage specimens showing the highest positive results (93%) followed by sputum (72%), nasal swabs (63%), faeces (29%), blood (1%) and urine (0%). 17 even though bronchoalveolar lavage and sputum have higher positive results, these should be avoided due to the possibility of aerosolisation of the virus and potential exposures to healthcare workers in the setting limited healthcare resources. this patient had several laboratory abnormalities that have been associated with worse outcomes including a serum neutrophil/lymphocyte ratio >3, 18 d-dimer >1000 ng/ml 19 and total lymphocyte count <0.8 (table 1) . 19 it is important to draw labs on presentation and periodically monitor throughout hospitalisation to project a patient's trajectory. when a patient is ultimately able to return home, quarantine is essential to preventing further spread of the virus. a test-based strategy is currently recommended to clear the patient from isolation which involves fulfilling all criteria including resolution of fever without antipyretics, improvement in respiratory symptoms and two negative covid-19 pcrs at least 24 hours apart. 20 this strategy may change based on the effectiveness of contact tracing and transmission of covid-19 prior to onset of symptoms or isolation. 21 at present, quarantine and negative covid-19 pcr confirmation remains the cornerstone in preventing transmission. finally, this case presents important public health considerations including how to allocate scarce critical care resources in a public health emergency. previously straightforward conversations with patients regarding their resuscitation status will change in a public health emergency. the act of performing cardiopulmonary resuscitation (cpr) on a patient with covid-19 potentially increases viral transmission to healthcare providers and requires use of scare personal protective equipment that could be used on patients with a higher chance of recovery. it has been suggested that attending physicians, during this covid-19 pandemic and a public health emergency, may withhold cpr from patients with or without covid-19 if they deem cpr to not be medically appropriate, even at the dissent of the patient or their representative. 'medically appropriate' is a term that takes into account the risk to healthcare workers performing cpr, the patient's prognosis if cpr was successful and that the patient would remain a priority to continue receiving critical care resources following cpr. 22 creation of an independent triage team with allocation criteria for intensive care admission and ventilation based on likelihood of long-term survival may also become important. this type of framework provides the greatest amount of help to the greatest number of people. 23 ultimately, if we are faced with a public health emergency and triage of scare resources, we will need to employ effective crisis leadership skills. these skills include being adaptable, empathetic, prepared, resilient, transparent and trustworthy. leadership during a crisis includes making decisions not based on reputation but rather based on the values of the group, organisation and community that the provider represents. 24 world health organization. coronavirus disease (covid-19) pandemic outbreak of pneumonia of unknown etiology in wuhan, china: the mystery and the miracle bats are natural reservoirs of sars-like coronaviruses detection of group 1 coronaviruses in bats in north america a pneumonia outbreak associated with a new coronavirus of probable bat origin probable pangolin origin of sars-cov-2 associated with the covid-19 outbreak tissue distribution of ace2 protein, the functional receptor for sars coronavirus. a first step in understanding sars pathogenesis structural basis of receptor recognition by sars-cov-2 clinical features of patients infected with 2019 novel coronavirus in wuhan, china coronavirus disease 2019 in elderly patients: characteristics and prognostic factors based on 4-week follow-up case report fellows may re-use this article for personal use and teaching without any further permission. become a fellow of bmj case reports today and you can: have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com. visit casereports coronavirus disease 2019: initial chest ct findings chest imaging using signs, symbols, and naturalistic images: a practical guide for radiologists and non-radiologists centers for disease control and prevention division of viral diseases. cdc 2019-novel coronavirus (2019-ncov) real-time rt-pcr diagnostic panel a patient with covid-19 presenting a false-negative reverse transcriptase polymerase chain reaction result false-negative results of real-time reverse-transcriptase polymerase chain reaction for severe acute respiratory syndrome coronavirus 2: role of deep-learning-based ct diagnosis and insights from two cases detection of sars-cov-2 in different types of clinical specimens neutrophil-to-lymphocyte ratio predicts severe illness patients with 2019 novel coronavirus in the early stage clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study centers for disease control and prevention. discharging hospitalized patients feasibility of controlling covid-19 outbreaks by isolation of cases and contacts guidance for decisions regarding cardiopulmonary resuscitation during the covid19 pandemic ? q= content/ model-hospital-policyallocating-scarce-critical-care-resources-available-online-now 6 critical components of effective crisis leadership contributors supervised by sbd. patient was under the care of ms, ak, amp and sbd. report was written by ms, ak, amp and sbd.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. patient consent for publication obtained.provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. matthew j samec http:// orcid. org/ 0000-0002-4736-6582 key: cord-327370-zo0n8wf6 authors: vadukul, prakash; sharma, deepak s; vincent, paul title: massive pulmonary embolism following recovery from covid-19 infection: inflammation, thrombosis and the role of extended thromboprophylaxis date: 2020-09-13 journal: bmj case rep doi: 10.1136/bcr-2020-238168 sha: doc_id: 327370 cord_uid: zo0n8wf6 covid-19 is the infectious disease caused by a recently discovered sars-cov-2. following an initial outbreak in december 2019 in wuhan, china, the virus has spread globally culminating in the who declaring a pandemic on 11 march 2020. we present the case of a patient with an initial presentation of covid-19 pneumonitis requiring mechanical ventilation for nearly 2 weeks and total admission time of 3 weeks. she was given prophylactic dose anticoagulation according to hospital protocol during this time. following a week at home, she was readmitted with acute massive pulmonary embolism with severe respiratory and cardiac failure, representing the first such case in the literature. our understanding of covid-19 continues to evolve as the disease remains a global public health emergency. a plethora of research has been conducted to investigate the disease process and the optimal treatment modalities but there still remain many unknowns. infection with sars-cov-2 is often asymptomatic but leads to deregulated immune responses with multiorgan failure and critical illness in a minority of patients. 1 this case examines aspects of covid-19 emphasising the increased thrombogenicity seen during infection and the potential need for extended anticoagulation following recovery particularly in those patients with severe illness and pre-existing risk factors. a 52-year-old woman with a background of obesity and undiagnosed type 2 diabetes mellitus was admitted to intensive care with breathlessness preceded by a week-long viral prodrome. admission chest radiography revealed diffuse bilateral infiltrates (figure 1) associated with severe type 1 respiratory failure (pao 2 /fio 2 ratio 75 mm hg prior to mechanical ventilation). after a 24-hour trial of continuous positive airway pressure, she deteriorated with tiredness, increased work of breathing and fluctuating conscious level. a confirmatory nasopharyngeal swab detected sars-cov-2 rna. following endotracheal intubation and mechanical ventilation, she underwent intensive care treatment for 2 weeks including airway pressure release ventilation, multiple sessions of prone positioning, antimicrobial therapy for secondary bacterial infection and continuous renal replacement therapy for 5 days. she gradually improved and after 11 days was successfully liberated from respiratory support without requirement of reintubation or tracheostomy. her condition continued to improve with rigorous physiotherapy and after step-down to the ward, she was successfully discharged home after a total 3-week inpatient stay. during her hospitalisation she received consistent doses of prophylactic low molecular weight heparin (lmwh) adjusted to her weight (101 kg, body mass index (bmi) 42) according to standard hospital protocol for venous thromboembolism (vte) prophylaxis. initially 60 mg of enoxaparin was administered subcutaneously once daily, increased to 40 mg two times per day after 4 days to reflect updated local anticoagulation protocols for those seriously affected by the disease. she was stepped down to ward from the intensive care unit and later at the time of discharge to home she was given insulin and antihypertensive medication to take away. lmwh was discontinued in keeping with standard hospital protocol predating any specific covid-19 guidance. one week later at 22:00 hours, she was brought to the emergency department by ambulance with severe breathlessness. she reported 2 days of rightsided chest pain with progressive dyspnoea culminating in syncope prior to presentation to the emergency department. on arrival the patient was conscious but unable to complete sentences. initial examination demonstrated a diaphoretic and agitated patient with unremarkable chest auscultation. the respiratory rate was 40/min and oxygen saturations were 85% on 15 l via a non-rebreathe device with a partial pressure arterial oxygen of 7.5 kpa. her systolic blood pressure was 80 mm hg with a heart rate of 130 beats/minute and cold peripheries. although alert she was confused and unable to give a clear history. she was apyrexial with unremarkable abdominal and lower limb examinations. electrocardiography demonstrated a sinus tachycardia and right heart strain suggested by subtle s-waves in lead i associated with q-waves and subtle t-wave inversion in lead iii. findings that shed new light on the possible pathogenesis of a disease or an adverse effect urgent ct pulmonary angiography (ctpa) was undertaken after initial management revealing bilateral pulmonary emboli with saddle component and right heart strain. bedside echocardiography after subsequent admission to intensive care revealed a dilated, impaired right ventricle and a 'd-shaped' left ventricle with pronounced left-ward septal deviation, more pronounced during systole indicative of pressure overload. during the initial presentation d-dimer levels were 1.2 fibrinogen equivalent units (feu) mcg/ml (normal range in our institution 0.0-0.50 feu mcg/ml). d-dimer levels at the time of her second admission were 8.1 feu mcg/ml. the clinical instability and refractory hypoxia warranted emergency rapid sequence induction and endotracheal intubation with intermittent boluses (10-100 μg) of epinephrine required to support her increasingly labile blood pressure. despite intubation, hypoxia persisted even after maximal oxygen delivery (fio 2 1.0), recruitment manoeuvres and optimisation of ventilation and patient position. urgent ct was arranged while thrombolysis was considered. other considerations during the initial patient assessment included secondary bacterial infection, atypical pnuemonia, cardiogenic pulmonary oedema and pulmonary embolism (pe). with the overall lack of clarity over the cause of her presentation and the uncertain nature of covid-19 with its unknown potential for relapse, confirmatory imaging was sought to confirm the diagnosis. with persistent severe hypoxia and hypotension, an urgent decision regarding administration of thrombolysis was required. intensive care personnel reviewed the images (figures 2 and 3) immediately after performance of the scan. we were able to accurately identify pulmonary emboli (subsequently confirmed on formal reporting an hour later), and this enabled immediate initiation of intravenous thrombolysis with tissue plasminogen activator (10 mg bolus of alteplase with subsequent 90 mg infusion over 30 min as per our trust protocol) within minutes of completion of ctpa, while still within the scanning room. she was admitted to intensive care to continue ventilation and inotropic support. overnight she was sedated, ventilated and required an epinephrine infusion (maximum dose 15 μg/min) to maintain an adequate mean arterial blood pressure. she made a rapid recovery. an initial fio 2 of 1.0 was required for 3 hours following endotracheal intubation likely due to significant shunt and deadspace ventilation with the large volume bilateral pe. however following thrombolysis there was a brisk improvement in her clinical condition with no requirement for vasopressors or inotropes at 12 hours post presentation and an fio 2 requirement of 0.5. she was successfully liberated from mechanical ventilation 16 hours later with no immediate neurological sequelae. after step-down to the ward long-term anticoagulation therapy was initiated after multidisciplinary discussion followed by discharge after 5 days. risk factors for thrombosis are numerous but are generally considered to contribute by three key mechanisms (virchow's triad); endothelial injury, reduced flow/stasis and hypercoagulable state. 2 although there are many unknowns with regard to this novel disease, increasing experience suggests that patients with severe covid-19 infection have elements of all three. 2 following initial discharge our patient was also noted to have reduced mobility and difficulty exercising with easy fatigability. allied to her obesity, a risk factor for vte, 3 this illustrates a picture of thromboembolic risk. pulmonary emboli has been reported frequently in covid-19 and are often noted in patients with covid-19 without other standard risk factors, suggesting that it is an independent risk factor for vte. 4 data from early french experiences revealed pe prevalence of 23% in patients with severe covid-19 infection. requirement for mechanical ventilation was also strongly linked to the presence of pe on imaging. 5 there is no current evidence to define the incidence of pe following recovery. at readmission this patient had little evidence of persistent infection with resolution of the majority of ground glass changes seen in prior imaging or other symptoms such as cough or fever. the duration of the prothrombotic state associated with covid-19 and therefore the optimal management strategy is unclear. 6 this case report aims to review the current literature regarding thromboprophylaxis in patients with covid-19 and highlights the potential for patient readmission after critical illness. with regard to the emergent management of pe, guidelines recommend thrombolysis where there is persistent haemodynamic compromise, evidence demonstrating survival benefit and improved long-term outcomes. 7 thrombolysis without cardiovascular compromise is controversial. 8 furthermore refractory hypoxia is not considered a typical indication for thrombolysis which is not without risk; reported rates of intracerebral haemorrhage of 1.7%. 7 however case reports and studies do suggest patients with profound respiratory failure may benefit from clot lysis. 8 9 it is worthwhile to note that while we administered thrombolysis for hypotension, there was marked improvement in gas exchange to go with stabilised blood pressure. sars-cov-2 is a single-stranded rna coronavirus. 10 common symptoms include fatigue, fever, headache, dyspnoea and myalgia. although advanced age and comorbidity (eg, hypertension, diabetes mellitus) are risk factors for developing serious illness, young and otherwise healthy patients can become critically unwell. 11 data from populations affected by the covid-19 demonstrate abnormal activation of the clotting cascade. 12 markers such as d-dimer concentration are associated with deleterious patient trajectory and increased incidence of mortality. 9 while covid-19 is typically associated with pneumonia, a multisystem inflammatory disorder and deregulated coagulation are at play leading to poor outcomes in those worst affected. 13 many pathways have been postulated to explain these extreme derangements in clotting. a syndrome of hyperinflammation is seen in those worst affected and it appears that parts of this cascade are responsible for coagulopathy. 14 it is widely accepted that the general endpoint of the inflammatory process is thrombosis. 15 thus immune system activation and subsequent inflammatory processes are intrinsically linked to clotting. common laboratory investigation abnormalities include a lymphopaenia, elevated c-reactive protein, ferritin, interleukin-6 (il-6, an inflammatory cytokine) and dramatically elevated d-dimers. 16 coagulation tests commonly reveal a prolongation of the prothrombin time and international normalised ratio alongside shortened activated partial thromboplastin times and ratios. 16 studies have implicated elevated expression of il-6 as a potential cause of endothelial dysfunction leading to thrombosis, 17 reinforced further by research implicating il-6 as a contributor to thrombotic risk in inflammatory conditions such as psoriasis. 18 initial data suggest that patients with complicated covid-19 infection have nearly three times the concentration of il-6 compared with those exhibiting less severe disease. 19 this highlights the importance of ongoing work examining the efficacy of il-6 inhibitors as an immunomodulatory therapy. 20 obesity in isolation is a risk factor for vte. the increased risk for vte is thought to be in part a result of the background chronic inflammatory state found in obese patients. hypertrophic adipose tissues lend to the over production of inflammatory cytokines such as tnf-a, interferon-g and il-6. these cytokines induce an inflammatory state the endpoint of which is an increase in procoagulant factors, increased tissue factor expression and augmented platelet activation. 3 patients with severe covid-19 infection are at risk of mortality and this risk is compounded by the presence of comorbidity including cardiovascular disease, diabetes mellitus and chronic obstructive pulmonary disease. obesity is additionally recognised as lending to poor outcomes in covid-19. 21 it appears possible that the obesity-related inflammation exacerbated by covid-19 mediated effects could lead to excess thrombosis in this group partly explaining the poorer outcomes seen in obese patients. thromboprophylaxis can take many forms, however a study by tang et al demonstrated a clear survival benefit in patients with covid-19 receiving lmwh as part of their treatment. severe covid-19 with either high d-dimers or high likelihood of sepsis-induced coagulopathy were shown to have improved rates of mortality when treated with lmwh at prophylactic doses. 22 appropriate use of lmwh may therefore have a central role to play in managing the sick population with covid-19. although classically considered an anticoagulant, heparin does have secondary properties which may have utility in the treatment of covid-19. its effects may have a role in disruption of clot production as well as ameliorating the inflammatory effects of thrombin. 23 heparin has been shown to have direct antiinflammatory properties including the antagonism of cytokines and sequestration of acute phase proteins. 24 the international society for thrombosis and haemostasis suggests that prophylactic treatment with lmwh is prudent in all patients with covid-19, particularly with severe disease or findings that shed new light on the possible pathogenesis of a disease or an adverse effect extreme derangements in clotting parameters. 25 regular monitoring of clotting parameters during admission with severe disease was also strongly recommended. the american college of cardiology suggests implementing extended courses of thromboprophylaxis in patients with covid-19 with other risks factors for vte for example, reduced mobility, pre-existing comorbidity or malignancy. d-dimer levels, greater than two times the upper limit of normal at point of discharge, have also been suggested as a guide for the initiation of prolonged anticoagulation treatment. 26 the british society of haematology advocates the use of lmwhs in the management of covid-19. 2 hospital-acquired vte is defined as any thrombotic event occurring within 90 days of hospital admission even after discharge. 2 compared with other populations, patients with covid-19 appear to have higher incidences of vte particularly with deranged clotting markers, critical care admission or reduced mobility. 2 reports from france and the netherlands revealed a high burden of thrombotic complications (primarily pe) despite routine prophylactic lmwh. 27 28 there were strong recommendations towards the use of vte prophylaxis for all patients requiring intensive care management and a low threshold for more aggressive anticoagulation strategies given the development of thrombotic complications in approximately one third of patients in intensive care despite prophylactic anticoagulation. 28 emerging antithrombotic guidance highlights the potential benefits of extended thromboprophylaxis beyond hospital admission. 29 several risk factors were identified including the presence of a d-dimer level twice the upper limit of normal at the time of potential discharge. 29 suggested regimens described courses of up to 45 days for adequate protection. other identified risk factors included patients over 60 years old, those with a past history of vte, active malignancy, reduced mobility, bmis>30 and recent stay in critical care. 29 these recommendations have subsequently been reflected in local guidelines produced shortly after our case. contributors pav and dss helped in conception or design of the work. prv performed data collection. prv and dss helped in drafting the article. pav, prv and dss performed critical revision and provided final approval of the version to be published. the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer reviewed. this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. deepak s sharma http:// orcid. org/ 0000-0001-7449-0346 learning points ► the case presented illustrates the wide reaching and prolonged sequelae of critical illness following covid-19 with complications occurring despite recovery from the acute phase of the illness. ► reduced mobility, easy fatigability and weakness in recovered patients are also likely to contribute to morbidity and mortality. ► given the still uncertain nature of covid-19 and its long-term effects on patients, there will be much to learn in the coming weeks and months regarding subsequent management of patients after the acute phase of the disease. ► further work may better characterise the thrombotic risks and identify appropriate management strategies. the role of thromboprophylaxis for mild cases of covid-19 in patients with significant risk factors remains unclear. these patients may be advised to self-isolate with resulting reduced levels of physical activity. ► it is also uncertain how long the proinflammatory/ prothrombotic state associated with covid-19 persists for after apparent resolution of the disease with regard to physical symptoms for example, oxygen requirement, fever. there are few recommendations for extended thromboprophylaxis but this case supports subsequent early guidance, which suggests it is beneficial in at-risk populations. we would advocate the use of a structured approach on a patient-to-patient basis, balancing thrombotic and bleeding risks. epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study practical guidance for the prevention of thrombosis and management of coagulopathy and disseminated intravascular coagulation of patients infected with covid-19 mechanisms of thrombosis in obesity acute pulmonary embolism and covid-19 pneumonia: a random association? acute pulmonary embolism associated with covid-19 pneumonia detected with pulmonary ct angiography scientific and standardization committee communication: clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with covid-19 esc guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the respiratory failure as an indication for thrombolysis in pulmonary embolism? thrombolysis in pulmonary embolism: are we under-using it? covid-19 infection: origin, transmission, and characteristics of human coronaviruses are patients with hypertension and diabetes mellitus at increased risk for covid-19 infection? abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia clinical predictors of mortality due to covid-19 based on an analysis of data of 150 patients from wuhan, china facing covid-19 in the icu: vascular dysfunction, thrombosis, and dysregulated inflammation blood coagulation in immunothrombosis-at the frontline of intravascular immunity coagulation abnormalities and thrombosis in patients with covid-19 interleukin 6 and haemostasis interleukin 6 regulates psoriasiform inflammationassociated thrombosis interleukin-6 in covid-19: a systematic review and metaanalysis sars-cov-2 and covid-19: is interleukin-6 (il-6) the 'culprit lesion' of ards onset? what is there besides tocilizumab? sgp130fc features of 20 133 uk patients in hospital with covid-19 using the isaric who clinical characterisation protocol: prospective observational cohort study anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy the versatile heparin in covid-19 more than an anticoagulant: do heparins have direct anti-inflammatory effects? isth interim guidance on recognition and management of coagulopathy in covid-19 covid-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: jacc state-of-the-art review high risk of thrombosis in patients with severe sars-cov-2 infection: a multicenter prospective cohort study incidence of thrombotic complications in critically ill icu patients with covid-19 emergence of institutional antithrombotic protocols for coronavirus 2019 key: cord-269703-d3yv9mcl authors: hori, arinobu; takebayashi, yoshitake; tsubokura, masaharu; kim, yoshiharu title: ptsd and bipolar ii disorder in fukushima disaster relief workers after the 2011 nuclear accident date: 2020-09-17 journal: bmj case rep doi: 10.1136/bcr-2020-236725 sha: doc_id: 269703 cord_uid: d3yv9mcl the global threat posed by the covid-19 pandemic has highlighted the need to accurately identify the immediate and long-term postdisaster impacts on disaster-relief workers. we examined the case of a local government employee suffering from post-traumatic stress disorder (ptsd) and bipolar ii disorder following the great east japan earthquake. the complex and harsh experience provoked a hypomanic response such as elated feelings with increased energy, decreased need for sleep and an increase in goal-directed activity, which allowed him to continue working, even though he was adversely affected by the disaster. however, 3.5 years later, when he suffered further psychological damage, his ptsd symptoms became evident. in addition to treating mood disorders, trauma-focused psychotherapy was required for his recovery. thereafter, we considered the characteristics of mental health problems that emerge in disaster-relief workers, a long time after the disaster, and the conditions and treatments necessary for recovery. the global threat posed by the covid-19 pandemic has highlighted the need to accurately identify the immediate and long-term postdisaster impacts on disaster-relief workers. we examined the case of a local government employee suffering from post-traumatic stress disorder (ptsd) and bipolar ii disorder following the great east japan earthquake. the complex and harsh experience provoked a hypomanic response such as elated feelings with increased energy, decreased need for sleep and an increase in goal-directed activity, which allowed him to continue working, even though he was adversely affected by the disaster. however, 3.5 years later, when he suffered further psychological damage, his ptsd symptoms became evident. in addition to treating mood disorders, trauma-focused psychotherapy was required for his recovery. thereafter, we considered the characteristics of mental health problems that emerge in disaster-relief workers, a long time after the disaster, and the conditions and treatments necessary for recovery. disasters continue to affect people not only in the moment of a disaster but also throughout the long-term recovery process. post-traumatic stress disorder (ptsd) and depression significantly impair the social functioning of those affected and are often recognised as the most visible mental health effects on survivors, as was the case with the great east japan earthquake (geje) of 2011. [1] [2] [3] [4] in the present study, however, we would like to focus on manic and hypomanic episodes that occurred in the victims of the geje. 5 6 while bipolar disorder requires medical treatment, social functioning of the patient tends to be maintained during the hypomanic episode. hypomanic patients show symptoms such as elated feelings with increased energy, decreased need for sleep and an increase in goaldirected activity. they could continue to contribute to the community as disaster-relief workers in the disaster-recovery process, which delays the recognition of their treatment needs by healthcare providers. the geje, which was followed by the nuclear accidents, left the affected areas severely damaged and required the victims to contribute as disaster-relief workers for a long period. 7 therefore, after the geje, not a few of the people involved may have continued to work as disasterrelief workers while exhibiting hypomania. in the general postdisaster context, relief workers are considered to be a group vulnerable to mental health problems 8 and have a higher incidence of late-onset ptsd. 9 this may be partly due to the fact that there are many opportunities for relief workers to come into contact with the misery of victims of disasters or adverse situations. in the case of the chernobyl disaster, the long-term effects on the mental health of the population who lived through the events are known. 10 11 the risk of mental disorder was particularly high among the workers involved in the clean-up efforts after the disaster because they were in constant fear of being exposed to radiation. [10] [11] [12] from this, one can infer the magnitude of the burdens borne by those engaged in the work of providing support to a community during any disaster. in the geje, the risk of mental disorder was also shown to be higher among disaster-relief workers, such as local government employees and tokyo electric power company officials. [13] [14] [15] in this case, being the target of blame and attacks from victims was a major factor contributing to increased risks. 14 15 in this study, we observed the emergence of bipolar ii disorder and symptoms of ptsd in a local government employee who experienced almost all the events of the geje disaster. even after the acute phase of the disaster, he continued to work diligently as a local government employee for more than 3 years. while he was forced to deal with social conflict caused by aspects of his job, he came across reports of floods in other parts of japan. consequently, he began experiencing symptoms of ptsd and major depressive episodes. the covid-19 pandemic is, at the time of writing, wreaking havoc around the globe in what is a major health disaster. during the pandemic, many people, including healthcare workers, are expected to work in appalling conditions for extended periods. therefore, understanding how the experience of a long-term, complex and severe disaster affects the mental health of essential responders (who are engaged in essential services) is important in guiding future policies and practices. the patient was a male in his 40s when he first visited our clinic. he was born and grew up in a town in fukushima prefecture (within 20 km of the nuclear power plant). after he graduated from a college in another city, he returned to his hometown and started working in a town office. he has no medical history of note. after the accident at the nuclear power plant in 2011, an evacuation global health order covering his hometown was issued. the order was lifted in july 2017. he was working at the town office at the time of the earthquake. later, while conducting a tour of the coastal area to check for earthquake damage and to ensure that people had evacuated, he experienced the tsunami near his childhood home. he and his colleague evacuated the lower floor of the house, moved upstairs with his family and watched as the surrounding houses were swept away, fearing that, along with his family and his colleague, he would also be swept away at any moment. eventually, the water receded, but the area around the house was flooded, preventing any movement. mobile phone services collapsed. in the evening, he carried his grandmother on his back and waded through the waters to take refuge on a nearby hill, where about 40 people had gathered. he barely slept during the night. at daylight the next day, he was rescued-along with the other people who were with him-by a self-defence forces helicopter. on the afternoon of the second day, he began engaging in relief work throughout the area. among the tasks and efforts he undertook was aiding the local fire brigade and he was involved in housing the corpse of a man whom he had known since childhood. he would go on to help recover six or seven bodies in half a day. with nowhere to go, he slept that night wrapped in a blanket by his desk in his office. he heard a rumour of a nuclear power plant being in danger and fell asleep in a daze. by the morning of the third day, it was clear that the nuclear power plant was in danger. evacuation orders for everyone within a 5 km radius, followed by a 10 km radius, from the nuclear power plant, were conveyed. on the night of the fourth day, the town office was closed. on the morning of the fifth day, he told his family to flee, although he decided to stay and aid in the relief work being carried out. on the morning of the seventh day, 200-300 people-taking refuge at a junior high schoolwere transported to another prefecture aboard seven or eight buses. there were only three staff members remaining, including himself. initially, he felt a strong sense of urgency and was in high spirits. he carried on working for 3 months with the local authorities, which included visiting evacuees. one of the evacuees once made him kneel for 2 hours, scolding him and saying, 'you're here too late'. even after he returned to his hometown, he continued to work as a local government employee. he was involved in a lot of heartbreaking work-such as catching and slaughtering the growing number of untended or escaped cattle and pigs within the evacuation area. in august 2014, after watching the news of the flood damage in another area of japan, he experienced flashbacks of scenes from the tsunami during the geje; these flashbacks made him anxious and made sleeping difficult. this affected his work severely. at that time, he was working in a department of the town and frequently attended briefings in his hometown. he notes that there was a lot of shouting at these briefings. in the same month, he visited a clinic in the city and was diagnosed with ptsd and depression. he was given leave from the time of his initial visit for a duration of about 8 months. his symptoms subsequently improved, and he decided to discontinue treatment. during this time, while taking antidepressant medication, he experienced an uptick in his mood and spent a lot of money on mail order goods besides elated feelings with increased energy, decreased need for sleep and an increase in goal-directed activity. two-and-a-half years later, he became depressed again and visited another psychiatric hospital in the city. this visit began a second leave of absence from his work; he returned to work after 4 months. three months later, he took a third leave of absence after suffering a worsening of his anxiety and depression. his physician, at the time, determined that he needed specialised treatment for ptsd and referred him to our clinic for the purpose of implementing trauma-focused psychotherapy. his first visit to our clinic was 7 years and 7 months after the geje. although outwardly he appeared well groomed, his speech was sluggish. his alcohol consumption increased after the disaster, but he had been abstaining from alcohol for a month and a half before his visit, so we told him to continue. the previous doctor's prescriptions were escitalopram (20 mg), mirtazapine (30 mg), ethyl loflazepate (4 mg) and diazepam (10 mg). although we considered this prescription inappropriate for a bipolar patient, we continued this treatment first then started to taper it down. after two general outpatient meetings, a total of 10 sessions of trauma-focused psychotherapy were conducted twice a week. weekly outpatient visits continued for a month. whenever he heard news about an earthquake on the tv, he became anxious; however, he had learnt to respond by practising breathing techniques. the psychotropic drugs were gradually reduced. he returned to work the next month, on a half-day basis, and began working full time after 3 weeks. at that time, he was still taking escitalopram (10 mg) and ethyl loflazepate (1 mg). we conducted prolonged exposure therapy. 16 17 in the first session, we listened in detail to comprehend all aspects of his trauma. because he had experienced multiple traumatic events, we asked him to evaluate the degree of subjective distress he felt about the different events. he expressed the following: (1) on the tsunami: 'i feel like blaming nature, wondering why this once-in-a-thousand-year event happened at this time'; (2) in reference to the harsh complaints emanating from residents after the disaster: 'it's not just my fault' and 'there's only so much i can do'; and (3) concerning the scene where corpses were taken: 'why did it have to be this way?' in the second session, he expressed survivors' guilt: 'there was some fear in the trauma part, but i wondered if the loss of an acquaintance was greater. the village where i was born and raised was gone. the person i told immediately after the earthquake to "get out of here fast" also died. i am wondering why i didn't tell them more forcefully. images of the disaster and [the sound of] sirens on fire trucks and ambulances trigger my anxiety. there were other times when we were all talking about the disaster and everyone was normal, and i was the only one who froze'. in the third session, he recalled that he was near his childhood home soon after the earthquake when the tsunami hit and how he had escaped by taking shelter on the second floor. he further recalled that he was left with others on high ground until the following day. in the fourth session, he described the first few days in detail. the moment the tsunami came, he was told: 'there's a tsunami coming, run away quickly'. he recalled that 'the waves were really black, and [that] the water was extremely powerful', and that he 'was rescued by a helicopter with [his] colleagues and [that he] went back to the town office crying'. in addition, on the afternoon of the 12 th , he was tasked with helping recover the deceased; the first person he found and carried was a fire brigade worker who he knew. in the fifth session, he remembered that, after recovering bodies on the afternoon of the 12th, he received the news that the nuclear power plant was in danger. in addition, after the evacuation order was issued, he had to help evacuate local residents while his family was evacuated to another area. there were times when he was subjected to abuse. he stated that: 'there's so much going on, so much work, it makes me just laugh'. in the sixth session, he was asked to explain, in detail, the scenes when the lifeless body of someone he knew was recovered. he had received a call from the fire brigade, telling him that a body had been found; subsequently, he was sent to pick it up. on recognising the corpse as someone he knew, he thought, 'i could have been dead, that could well have been me rather than him'. in the seventh session, he could recall and express his memories more easily than previously. he said, 'it's over, but why did it take so long?' in the eighth session, we dealt with the tsunami scene again and he recalled the episodes in greater detail. in the ninth session, he was asked to speak about his recollections of the first 3 months after the earthquake and how he lost 15 kg of weight during that period, resulting in a colleague telling him that he looked completely different. in the tenth session, he was asked to repeat his recollections of those first 3 months. he responded by saying that 'it's great that i've been able to organize the memories in my head. before, they were all jumbled up. i have been able to cut out some of the worst traumatic experiences, organize others, and accept the result. so, i've come to understand that it's all in the past'. the patient continued his visits to the outpatient clinic as well as his medication-mainly the mood stabiliser lamotrigine (25 mg: in japan, the dosage of each psychotropic drug is usually set lower than in western countries) used for the treatment of bipolar disorder. he voluntarily practised coping techniques, such as breathing exercises, in situations where he felt stressed. every year, emotional instability emerged around 11 march, the day the earthquake struck. in october 2019, the area where the disaster occurred suffered from flooding and water damage due to a major typhoon. he was involved in the management and operation of the evacuation centre that was set up at that time, but later became unwell and needed to take a leave of absence for about a month. trauma-focused psychological interview sessions were conducted following this event, and two traumatic memories were treated, which were left unaddressed in the prolonged exposure method interviews conducted. one recollection concerned the times when he was angrily abused by some evacuees during the period after the geje. the second was about the scene when he was verbally abused at his job. after the two sessions, he recovered and has returned to work and continues to be well. the covid-19 outbreak, which began in january, has caused intense and extensive fear and anxiety. the patient has reported that the outbreak has brought back memories of the geje, as well as that of the atmosphere of the people at the time, causing him to experience some heightened emotions of fear. he has also realised, however, that for a long time he was too absorbed in and preoccupied by his geje experiences; because of this awareness and acceptance, he was mindful not to be like that this time round. how do the complex and harsh experiences of the geje disaster and its aftermath affect disaster-relief workers? the geje was a complex disaster that involved an earthquake, tsunami and nuclear power plant accident, followed by a series of compulsory evacuations. what are the crucial aspects of the trauma caused by complex disasters? what kind of response does such trauma provoke in the short term and what are the long-term consequences? what kind of measures should be taken to deal with mental health problems caused by complex disasters, including nuclear disasters? important characteristics of the traumatic events experienced by disaster-relief workers in complex disasters, including nuclear accidents, and as demonstrated throughout this case, are as follows: 1. they intermittently experience multiple traumatic events over an extended period. 2. the impact of being caught up in social conflicts over nuclear power and radiation exposure is significant, as is receiving strong condemnation and attacks from residents. 14 15 considering these two points, two further observations can be made: 3. in addition to the magnitude of the trauma or loss experienced, there may be a mildly manic reaction to dealing with persistent crisis situations in the community at large. in this psychological defence reaction, there is a risk that mental health problems, such as depression and ptsd, would appear or develop a few years after the disaster. 4. anxiety concerning the health effects of radiation exposure, which is generally considered to be a problem following nuclear disasters, 8 10 18 19 might be neglected. this patient experienced the geje as a local government employee and had an extremely harsh and traumatic time in the months following the disaster. these included the recovery operations, a fear of exposure to radiation, harsh living conditions following the evacuation, separation from his family, and strong condemnation and reprimands as a result of postdisaster social strife and conflicts. despite this strong psychological burden, this individual continued to work diligently for the recovery and reconstruction of the community, which illustrated the strength of his resilience. it is believed that participation in the altruistic activity of contributing to the recovery of the community boosted that resilience. 20 at the same time, it is worth noting that in the present case, the patient demonstrated a hypomanic state. the hypomanic state is pathological, as it involves the avoidance of realistic anxiety. 21 denial of self-damage or fatigue can make selfcare more difficult to implement. however, in the short term, it produces desirable effects by maintaining social activity, which can protect people from being overwhelmed by practical challenges in a disaster situation. this may be an adaptive response which enhances resilience. we would like to draw attention to the fact that the patient did not complain of anxiety concerning the adverse health effects of radiation exposure, which is generally expected in mental health problems associated with nuclear disasters. 8 10 18 19 as in the present case, this may be due to the fact that residents who choose to live in relatively close proximity to the accident site can be seen as a biassed group that does not take the possible global health damage of radiation exposure seriously. it is also possible to think that a manic avoidance of anxiety 21 may be at work here. alternatively, it could be an outcome of the risk communication 22 that took place after the disaster. people living in the area had learnt that the levels of radiation that they were exposed to while living in close proximity to the plant were not the kind that would actually have serious consequences. three years and 5 months after the disaster, the ptsd symptoms-including flashbacks-suddenly flared up after the patient was exposed to news of another disaster in japan. in addition, during this period, the patient endured a situation in which he was required to negotiate, as a representative of the local government (being an employee himself), with residents who were affected by the nuclear accident. however, communication and negotiations did not go well, resulting in strong admonishment. in the case of an elderly woman with symptoms of ptsd caused by the tsunami, as reported by hori et al, the recurrence was also caused by being involuntarily blamed for being involved in a severe conflict among residents in the communal dwelling where she was living. 23 although our patient recovered from his mood disorder by using medication, he had two repeated flare-ups which led to the implementation of prolonged exposure therapy 16 17 -a psychotherapy focused on ptsd. north and pfefferbaum have argued that less invasive treatments should be prioritised in the immediate aftermath of a disaster as an intervention for post-disaster ptsd, and specialised trauma-focused treatments should be provided only when depression and ptsd symptoms persist. 24 our treatment is consistent with this argument. the actual psychotherapy process involved sorting out a situation in which multiple traumatic events were intricately intertwined, in addition to habituation through the recall of traumatic memories. we also discussed the destruction of his hometown and the loss of his relatives and acquaintances. 16 although improvement was observed following the treatment described previously, emotional instability was sometimes caused by increased stress in daily life; as such, it was necessary to continue the outpatient treatment, including the prescription of lamotrigine (25 mg). we also provided psychological education about stress coping. although trauma reactions and feelings of depression may intensify on the anniversary of the geje, he gradually became able to care for himself. in addition, we discussed his tendency to be manically uplifted in crisis situations and overly immersed in his community contributions. however, the traumatic experience of receiving strong condemnation from residents 14 15 -that could not be addressed in the initial ptsd treatment-necessitated additional psychotherapeutic interviews later on. on the other hand, we should not rely solely on improving the coping skills of patients. because experiencing multiple disasters would increase the suicide rate, 25 the same person should not be repeatedly burdened as a relief worker. the following lessons can be drawn from this case: 1. the recovery and reconstruction of the community, including a medical system that allows general psychiatric treatment, such as treatment for mood disorders, should be ensured as quickly as possible after a disaster. 2. it is not easy for those who have an important role in the affected community to reduce their responsibilities in the community during the postdisaster phase. there is also a prejudice against psychiatric issues. awareness-raising activities related to mental health, including psychoeducation about symptoms of mood disorders and ptsd, should be carried out widely in the community, even though this could be difficult after the disaster. the medical facilities where the cur-rent treatment was provided also existed in the areas affected by the disaster. 26 27 3. a system that allows access to specialised treatment focused on ptsd should be developed 16 17 23 when necessary. 4. the public should be made aware that they should refrain from unwarranted severe criticism of local government officials in the wake of a disaster, 14 15 as it would increase the risk of mental health problems for those who are criticised. â�º for the victims of the great east japan earthquake who experienced the earthquake, tsunami, nuclear accident and subsequent evacuation, there are two highly significant points: (1) the persistence of the crisis situation over a long period (weeks, months or even years) and (2) the emergence of social conflicts over radiation exposure from an early stage. â�º in particular, disaster-relief workers are at a high risk of mental health problems because they are repeatedly exposed to other victims' tragic situations and are prone to be strongly criticised or attacked, even though they themselves are victims of the disaster. â�º with respect to postdisaster mental health, both depression and hypomania may emerge. since hypomania is a partial disavowal of difficult realities, decrease in anxiety and increasing physical activity can represent an adaptive response to difficult situations arising after a complex disaster, including a nuclear disaster where the threat is invisible. â�º exposure to radiation after a nuclear accident can damage mental as well as physical health, both or either of which may not manifest for some considerable time after the initial disaster, or which may appear following various trigger events. â�º in postdisaster patients, mood disorders that are combined with post-traumatic stress disorder (ptsd) may not be controlled without ptsd-focused treatment. psychological distress after the great east japan earthquake and fukushima daiichi nuclear power plant accident: results of a mental health and lifestyle survey through the fukushima health management survey in fy2011 and fy2012 severe psychological distress of evacuees in evacuation zone caused by the fukushima daiichi nuclear power plant accident: the fukushima health management survey mental health and psychological impacts from the 2011 great east japan earthquake disaster: a systematic literature review psychiatric outpatients after the 3.11 complex disaster in fukushima mental disorders that exacerbated due to the fukushima disaster, a complex radioactive contamination disaster newly admitted psychiatric inpatients after the 3.11 disaster in fukushima report from minamisoma city: diversity and complexity of psychological distress in local residents after a nuclear power plant accident a systematic review of health outcomes among disaster and humanitarian responders occurrence of delayed-onset post-traumatic stress disorder: a systematic review and meta-analysis of prospective studies mental health consequences of the chernobyl disaster a 25 year retrospective review of the psychological consequences of the chernobyl accident mental health and alcohol problems among estonian cleanup workers 24 years after the chernobyl accident factors related to the fatigue of relief workers in areas affected by the great east japan earthquake: survey results 2.5 years after the disaster longitudinal effects of disaster-related experiences on mental health among fukushima nuclear plant workers: the fukushima news project study the longitudinal mental health impact of fukushima nuclear disaster exposures and public criticism among power plant workers: the fukushima news project study emotional processing of fear: exposure to corrective information efficacy of prolonged exposure therapy for a patient with late-onset ptsd affected by evacuation due to the fukushima nuclear power plant accident longitudinal associations of radiation risk perceptions and mental health among non-evacuee residents of fukushima prefecture seven years after the nuclear power plant disaster changes in risk perception of the health effects of radiation and mental health status: the fukushima health management survey 6 keys to resilience for ptsd and everyday stress coping styles of outpatients with a bipolar disorder building risk communication capabilities among professionals: seven essential characteristics of risk communication enhancement of ptsd treatment through social support in idobata-nagaya community housing after fukushima's triple disaster mental health response to community disasters: a systematic review suicidality risk and (repeat) disaster exposure: findings from a nationally representative population survey hospital staff shortage after the 2011 triple disaster in fukushima, japan-an earthquake, tsunamis, and nuclear power plant accident: a case of the soso district mental health crisis in northeast fukushima after the 2011 earthquake, tsunami and nuclear disaster acknowledgements we thank all those who contributed to the recovery from the great east japan earthquake.contributors ah was the main therapist of the case and wrote the initial manuscript. yt and mt critically revised the manuscript. yk supervised the case. all authors contributed to the refinement of the paper and approved the final manuscript. key: cord-331193-33cyvidx authors: mawhinney, jamie a; wilcock, catherine; haboubi, hasan; roshanzamir, shahbaz title: neurotropism of sars-cov-2: covid-19 presenting with an acute manic episode date: 2020-06-14 journal: bmj case rep doi: 10.1136/bcr-2020-236123 sha: doc_id: 331193 cord_uid: 33cyvidx a 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. he was sexually disinhibited with pressured speech and grandiose ideas. his behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (sars-cov-2). neuroimaging and a lumbar puncture were normal. initial screening for sars-cov-2 in the cerebrospinal fluid was negative although no validated assay was available. the patient’s mental state remained abnormal following stepdown from intensive care. psychiatric assessment found features consistent with acute mania, and he was detained under the mental health act. this case indicates the need to consider covid-19 in a wider series of clinical presentations and to develop a validated assay for sars-cov-2 in the cerebrospinal fluid. a 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. he was sexually disinhibited with pressured speech and grandiose ideas. his behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (sars-cov-2). neuroimaging and a lumbar puncture were normal. initial screening for sars-cov-2 in the cerebrospinal fluid was negative although no validated assay was available. the patient's mental state remained abnormal following stepdown from intensive care. psychiatric assessment found features consistent with acute mania, and he was detained under the mental health act. this case indicates the need to consider covid-19 in a wider series of clinical presentations and to develop a validated assay for sars-cov-2 in the cerebrospinal fluid. covid-19 is an acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (sars-cov-2). 1 the virus was identified as the cause of an outbreak of pneumonia in hubei province, china, in december 2019 and has spread globally, so far responsible for over 2 million cases and 150 000 deaths worldwide. 2 sars-cov-2 is the seventh coronavirus known to infect humans and is a member of the orthocoronavirus subfamily. 3 it appears to be principally transmitted via respiratory droplets and contact with surfaces conveying the pathogen. 3 entry into the host cells is reportedly via the ace-2 receptor. 4 the most common initial symptoms of covid-19 are fever, dry cough, fatigue and myalgia. 5 the primary complication is acute lung injury resulting in type 1 respiratory failure, with a significant proportion requiring intensive care unit admission. 6 7 however, in addition to these respiratory features, the disease affects multiple organs including the cardiovascular system and gastrointestinal system. 4 6 8 there have been few case reports of primarily neurological presentations of the disease. [9] [10] [11] [12] this article outlines a case of covid-19 presenting with an acute manic episode necessitating emergency intubation and discusses potential mechanisms for the development of neuropsychiatric disease. a 41-year-old man with no significant medical history other than congenital nystagmus presented to the emergency department in the early hours of the morning. he had woken at night restless, agitated and reported feeling like his 'brain was racing'. he told his wife that he felt like he was 'going to die'. he also confessed to numerous hitherto undisclosed homosexual encounters and other sexual behaviours described as uncharacteristic by his wife. this acute presentation was preceded by a 1-day history of severe occipito-parietal headache, described as the 'worst headache ever', and a 10-day history of a dry cough and fever. his wife also reported similar but milder symptoms. he did not report anosmia. he had no significant smoking or alcohol history and denied any illicit drug use. he did however report a severe transient mood reaction with some possible paranoid features to cannabis in 2004 with no further use since then. his sister had a previous episode of postpartum psychosis and was subsequently diagnosed with bipolar disorder. physical examination revealed fine bibasal inspiratory crepitations and a nystagmus in all directions. neurological examination was otherwise normal. his mental state examination however was abnormal. he was loud and highly aroused with sexual disinhibition and overfamiliar behaviour, inappropriately questioning and touching members of staff. his speech was pressured, and his mood subjectively and objectively elevated. his thoughts were grandiose with persecutory elements, and he had persistent strong religious ideas, manifestations of which included attempts to anoint fellow patients with water. he also obsessively wrote down every personal interaction and bodily sensation. he said he found this experience 'liberating'. he did not report visual or auditory hallucinations. this abnormal behaviour worsened while in the emergency department to the point where it was deemed necessary for him to be transferred to intensive care for sedation and mechanical ventilation despite no respiratory indication. a nose and throat swab taken on admission subsequently tested positive for the presence of sars-cov-2 viral rna and chest x-ray showed features consistent with a covid-19 pneumonitis. bloods results during admission are shown in table 1. his crp and neutrophils were raised initially but new disease settled shortly after admission, as did his mild lymphopaenia. liver function tests were initially normal, but he developed a mild transaminitis soon after admission. thyroid stimulating hormone, b12 and folate were normal. serological screening was negative for hiv antigen and antibody, hepatitis b surface and core antigen, hepatitis c igg antibodies and treponema pallidum antibodies. no common autoantibodies were found in the serum, apart from mildly raised hep2 antinuclear antibodies of uncertain significance. a coeliac screen was also negative, as were n-methyl-d-aspartate receptor (nmda) and voltage-gated k+ channel autoantibodies. ct and mri brain showed no acute intracranial pathology or evidence of encephalitis. a lumbar puncture with normal opening pressure demonstrated gin-clear cerebrospinal fluid (csf) and no erythrocytes, leucocytes or other organisms. glucose level in the csf has 4.8 mmol/l (plasma glucose 8.4 mmol/l) and protein level 0.19 g/l. the sample was also was negative for herpes simplex virus dna, varicella zoster virus dna, enteroviorus rna and parechovirus rna not detected. initial screening for sars-cov-2 in the csf were also negative, although a validated assay was not yet available making interpretation difficult. empirical antimicrobial and antiviral treatment to cover for bacterial meningitis, community-acquired pneumonia and viral encephalitis were commenced but ceased after 48 hours in the absence of any evidence of ongoing infection on clinical and biochemical investigation. the patient was extubated after less than 24 hours of mechanical ventilation and moved to a level one ward environment. the patient's respiratory symptoms settled within 2 days of step down, but his mental state remained abnormal. an addenbrokes cognitive examination scored 90/100 with 18/18 in attention tasks and 25/26 in memory tasks while a frontal assessment battery scored 14/18 losing points for inhibitory control and lexical fluency and motor assessment. by day 8, his behaviour had escalated further culminating in a security call and emergency sedation for the safety of himself, the ward staff and other patients. he was subsequently detained under section 2 of the mental health act 1983, transferred to an acute inpatient psychiatric hospital and commenced on regular olanzapine. during this admission, he continued on regular antipsychotics and benzodiazepines for sedation. he required transfer to the emergency department while still an inpatient where he was investigated for severe left-sided chest pain. a ct pulmonary angiogram confirmed ongoing inflammatory changes consistent with covid-19 pneumonitis but no other pathology. as the ambulance came, i confessed to my wife that i had sex with men (most of which before marriage), although i am heterosexual. i felt that i was incapable of lying or hiding the truth and thought i was dying. i was in hospital for a total of 20 days with psychosis and mania, which i experienced as fascinating. this may seem strange from an outside perspective, but i was, in my mania, trying to help the doctors as much as i could, while at the same time trying to make sense of my condition. i began to think that i was part of a tv show, in which i was sent back from the future to save the nhs, and i was curious to see how this would end. for my family and friends it was frightening. luckily, they had a lot of support from each other, and from the great team of doctors at st. thomas hospital. ► covid-19 manifests in a number of ways affecting multiple systems including the central nervous system (cns). ► the neuroinvasive potential of the severe acute respiratory syndrome coronavirus 2 (sars-cov-2) (neurotropism) has been reported, but the pathophysiology remains unclear with uncertainty over its long-term consequences. ► there are multiple effects of sars-cov-2 virus on the cns, and currently, there are no specific treatment options available particularly for the neurotropic sequelae. ► further research is needed to develop a validated assay for sars-cov-2 in the cerebrospinal fluid. his mania improved on return to the psychiatric unit, and he was discharged 12 days after instigation of the section 2 order. his medications on discharge included olanzapine 10 mg daily with a plan to reduce this to 7.5 mg within the next week and 1 mg twice daily of clonazepam also to be weaned in the community. at follow-up 23 days from the original presentation, he was well at home, and he and his wife reported that he was now at his baseline level of function. this report outlines a rare case of acute mania associated with sars-cov-2 infection. this was particularly severe, necessitating emergency intubation and subsequent inpatient psychiatric admission. although this may represent a first episode of a primary psychiatric condition such as bipolar disorder, it is also important to consider other organic disease given the simultaneous diagnosis of covid-19. although it is not yet possible to confirm here due to the lack of a validated csf-pcr assay, previous reports have implicated sars-cov-2 in the development of viral encephalitis, and this remains an important differential. 9 12 in one of the initial reports on patient presentations and outcomes from wuhan, confusion accounted for 9% of reported symptoms, although the nature of these episodes was not expanded on. 7 in addition to this, there are further reports of covid-19 causing acute haemorrhagic necrotising encephalopathy and acute inflammatory neuropathy in guillain-barre syndrome. 10 11 an acute delirium was also considered, although the absence of a fluctuating course and inattention as key features made this less likely. neurotropism of sars-cov-2 has been tentatively reviewed in the literature. the entry of sars-cov-2 into human host cells is mediated mainly using ace-2 as a receptor, and although the lungs and the gastrointestinal tract are the principle sites of expression of ace-2 in the body, the protein is also expressed throughout endothelial cells in the brain providing a theoretical route of entry into the central nervous system. 13 14 more specifically, the amygdala, which has key functions in emotional intelligence as well as those related to sexual arousal, has been demonstrated to express ace-2 in animal models thus providing a focus to which the spike proteins of the virus may bind. 15 it has also been hypothesised that the virus may enter via peripheral nerve terminals. 16 neurological invasion of the virus therefore may represent another potential aetiology for this acute illness in absence of any other biological, psychology or social precipitating factors. this is, to the best of our knowledge, the first report of an acute episode of mania or psychosis as a result of sars-cov-2 infection. the pathophysiology of this is yet to be discerned, but given the temporal relation, we are led to assume that viral infection mediated this presentation. the ideal treatment modality for neuropsychiatric manifestations of covid-19 and the long-term prognosis of such cases remain to be seen. this case indicates the need to consider testing for and diagnosis of covid-19 in a wider series of clinical presentations including new onset psychiatric and neurological disorder. more research is required to look at the neurological manifestations of covid-19, as well as a need to develop a validated assay for sars-cov-2 in the csf in order to determine the neuroinvasive potential of the virus. pathological findings of covid-19 associated with acute respiratory distress syndrome world health organisation. who covid-19 dashboard the epidemiology and pathogenesis of coronavirus disease (covid-19) outbreak covid-19 and the cardiovascular system clinical characteristics of coronavirus disease 2019 in china clinical features of patients infected with 2019 novel coronavirus in wuhan, china epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in wuhan, china: a descriptive study covid-19 and the gastrointestinal tract: more than meets the eye neurological complications of coronavirus disease (covid-19): encephalopathy permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission. become a fellow of bmj case reports today and you can: have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com. visit casereports.bmj guillain-barré syndrome associated with sars-cov-2 infection: causality or coincidence? covid-19-associated acute hemorrhagic necrotizing encephalopathy: ct and mri features a first case of meningitis/encephalitis associated with sars-coronavirus-2 tissue distribution of ace2 protein, the functional receptor for sars coronavirus. a first step in understanding sars pathogenesis evidence of the covid-19 virus targeting the cns: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central mas receptors the neuroinvasive potential of sars-cov2 may be at least partially responsible for the respiratory failure of covid-19 patients contributors all authors were the acute medical team managing the patient. jam wrote the manuscript and cw, hh and sr reviewed the manuscript and provided insight into further research in the field.funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.competing interests none declared. patient consent for publication obtained.provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. orcid id jamie a mawhinney http:// orcid. org/ 0000-0002-7851-7953 key: cord-300183-z3fwtwqb authors: ahmed, taha; lodhi, samra haroon; kapadia, samir; shah, gautam v title: community and healthcare system-related factors feeding the phenomenon of evading medical attention for time-dependent emergencies during covid-19 crisis date: 2020-08-25 journal: bmj case rep doi: 10.1136/bcr-2020-237817 sha: doc_id: 300183 cord_uid: z3fwtwqb the current covid-19 crisis has significantly impacted healthcare systems worldwide. there has been a palpable increase in public avoidance of hospitals, which has interfered in timely care of critical cardiovascular conditions. complications from late presentation of myocardial infarction, which had become a rarity, resurfaced during the pandemic. we present two such encounters that occurred due to delay in seeking medical care following myocardial infarction due to the fear of contracting covid-19 in the hospital. moreover, a comprehensive review of literature is performed to illustrate the potential factors delaying and decreasing timely presentations and interventions for time-dependent medical emergencies like st-segment elevation myocardial infarction (stemi). we emphasise that clinicians should remain vigilant of encountering rare and catastrophic complications of stemi during this current era of covid-19 pandemic. the current covid-19 crisis has significantly impacted healthcare systems worldwide. there has been a palpable increase in public avoidance of hospitals, which has interfered in timely care of critical cardiovascular conditions. complications from late presentation of myocardial infarction, which had become a rarity, resurfaced during the pandemic. we present two such encounters that occurred due to delay in seeking medical care following myocardial infarction due to the fear of contracting covid-19 in the hospital. moreover, a comprehensive review of literature is performed to illustrate the potential factors delaying and decreasing timely presentations and interventions for time-dependent medical emergencies like st-segment elevation myocardial infarction (stemi). we emphasise that clinicians should remain vigilant of encountering rare and catastrophic complications of stemi during this current era of covid-19 pandemic. a dramatic and perplexing drop in st-segment elevation myocardial infarction (stemi) admissions has been observed during the current covid-19 crisis. anecdotal evidence suggests that the principal reason behind this is patient's anxiety to avoid seeking medical care at hospitals and overwhelmed healthcare systems due to the pandemic. 1 patients are less inclined to visit hospitals with fear of acquiring covid-19. many patients with risk factors of stemi may dismiss their angina symptoms as benign relative to this fear. this attitude of medical care avoidance has led to delay in hospital presentations, with dire consequences. 2 furthermore, the covid-19 pandemic has impacted the healthcare system's maintenance of operational integrity of high-acuity patients. 3 herein, we chronicle two cases of delayed presentations of stemi with rare complications that we encountered at our centre in the month of april 2020. both patients belonged to the cuyahoga county of the state of ohio, usa. they avoided medical care for a timedependent medical emergency, despite having good social and financial support and easy access to tertiary percutaneous coronary intervention (pci) capable healthcare facilities. 4 their dramatic presentation of stemi with a complicated clinical course and outcomes could have been prevented by an early referral to emergency medical services. this was the time period when the cuyahoga county was one of the most severely affected regions of ohio with the most covid-19 fatalities reported across the state. 5 patient 1 is a 62-year-old caucasian woman who presented to the emergency department (ed) with shortness of breath and dizziness for 1 day. she stated having nausea and diarrhoea for 2 weeks, associated with intermittent chest pain. she was hesitant getting medical attention and her symptoms got complicated with shortness of breath and dizziness. her medical history is significant for lifelong cigarette smoking, obesity (bmi of 38 kg/ m 2 ) and untreated hyperlipidaemia. on presentation, she had a blood pressure of 96/69 mm hg, heart rate of 89 beats per minute (bpm), temperature of 98.7°f and respiratory rate of 14 breaths/ minute. physical examination showed an anxious woman with cold extremities, tachycardia with no murmurs and increased effort of breathing with a benign abdominal examination. while in the emergency room, patient became haemodynamically unstable and her rhythm converted to ventricular tachycardia (vt) requiring successful cardioversion on three subsequent occasions following which she was transferred to the intensive care unit (icu) for vt storm. ecg revealed a wide complex tachycardia at a rate of 200 bpm (figure 1a), high sensitivity troponin t (tnt) was 1151 mg/l (normal <12 mg/l) and probnp of 34 430 pg/ml (normal <125 pg/ml). covid-19 testing with nasopharyngeal swab was negative and chest x-ray revealed bilateral opacities. complete blood count showed leucocytosis, serum lactate 6.6 mmol/l (normal 0.5-2.2 mmol/l), alanine aminotransferase 6497 u/l (normal 7-38 u/l) and aspartate aminotransferase 14 739 u/l (normal 13-35 u/l). synchronised cardioversion with three successive shocks were performed for vt storm, with global health conversion to sinus rhythm with repolarisation changes in inferior leads (figure 1b). she was intubated and transferred to icu on infusion of amiodarone and lidocaine. over the next hour, she became progressively hypotensive with cold extremities requiring vasopressor support. a transthoracic echocardiogram (tte) revealed severely reduced biventricular function. patient was transferred to the cardiac catheterisation laboratory, left and right heart catheterisation (lhc/rhc) performed. rhc revealed the patient to be in cardiogenic shock (table 1) . lhc revealed total occlusion of the mid-distal right coronary artery (rca) and 90% stenosis of the left anterior descending artery (lad) (figure 2a and b). during an attempt to cross the rca lesion with a guidewire, patient became asystolic. advanced cardiac life support was instituted with return of spontaneous circulation in 3 min. a temporary pacemaker was implanted and three drug eluting stents were placed in the rca with timi 2 flow post-revascularisation. due to small diameter iliac arteries, an intra-aortic balloon pump was favoured over an impella device for haemodynamic support for cardiogenic shock. patient was transferred to the icu with an augmented systolic blood pressure of 70 mm hg. she became progressively acidotic despite haemodynamic support and her lactate climbed to 9.1 mmol/l, indicating worsening cardiogenic shock. haemodynamic support was escalated to venoarterial extracorporeal membrane oxygenation (va-ecmo). patient remained on va-ecmo for 6 days and was successfully decannulated on day 7. repeat tte revealed mildly decreased systolic function with an left ventricular ejection fraction (lvef) of 50%. patient is currently recovering on the regular medical floor. patient 2 is an 82-year-old caucasian woman who presented to the ed with worsening shortness of breath and leg swelling for 2 days. her history included coronary artery disease (cad) with remote angioplasty in 1995, peripheral vascular disease, hypertension, hyperlipidaemia, gastro-oesophageal reflux disease and chronic smoking. she reported waking up with chest pressure followed by vomiting 12 days prior to presentation. she was reluctant to visit the ed in ongoing viral pandemic and instead visited her primary care physician's office. ecg during the office visit was unremarkable, her symptoms were considered atypical and she was sent home on pantoprazole. however, new onset worsening shortness of breath prompted her to report to the ed. on presentation, she had a blood pressure of 116/77 mm hg, heart rate of 97 bpm, temperature of 97.1°f and respiratory rate of 21 breaths/minute. physical examination revealed a systolic murmur in the third intercostal space along the left sternal border and crackles in the lung bases. ecg revealed st-segment elevations in leads v2-v6 with q waves in leads i, avl, v5-v6 (figure 3). tnt was elevated to 0.718 ng/ml (normal 0-0.029 ng/ml) and probnp was 13 346 pg/ml. patient was administered aspirin 325 mg and clopidogrel 300 mg and started on a heparin infusion. an emergent tte revealed severely decreased lv function with an ef of 30%, right ventricular systolic pressure of 57 mm hg and a muscular ventricular septal rupture in the mid anteroseptal wall (figure 4). patient underwent combined lhc/rhc with saturation study. rhc was significant for a pulmonary capillary wedge pressure of 28 mm hg and lhc revealed acute total occlusion of the proximal lad, diffuse 40% stenosis in the lcx, 70% stenosis of ramus intermedius and 40% stenosis of mid-rca (figure 5a-c). a left ventriculogram confirmed a muscular ventricular septal rupture (vsr) ( figure 5d ). there was oxygen step up in the right ventricle and pulmonary artery and the qp/qs was 1.56 (table 2) . conservative management of the cad was pursued of concerns for reperfusion injury of infarcted myocardium. patient was discharged home on dual antiplatelet therapy, high-intensity statin, beta-blocker and daily furosemide. on a follow-up visit, 1 week after discharge, patient reported worsening shortness of breath at rest. the symptoms were deemed secondary to increased shunting across the vsr. her ecg showed q waves in the inferior leads with residual st-segment elevations. a cardiac mri showed a small defect in the mid-anteroseptum (figure 6). patient underwent percutaneous closure of vsr and tolerated the procedure well. currently, the patient is recovering on the medical floor with no symptoms of angina or heart failure. there is a delay and decrease in presentations and timely interventions for medical emergencies like stemi during the current era of covid-19 crisis. there is a resultant increase in mechanical and arrhythmogenic complications of stemi as a presenting encounter, a rarity in the age of primary ppi (ppci). healthcare providers need to be vigilant in identification and management of late presentations of stemi and its complications. acute stemi is the major cause of mortality globally. it is well established that early diagnosis and immediate reperfusion with ppci are the most effective to improve outcomes by lowering risk of post-stemi complications. 6 however, the covid-19 outbreak has threatened to overwhelm healthcare systems worldwide, potentially overshadowing other medical emergencies, including stemi. 7 the data from various countries of europe show a 25%-40% drop in stemi presentations and admissions as compared with during the peak of pandemic. [8] [9] [10] in the usa, a comparable decrease in stemi presentations is reported in different states irrespective of the state's burden of covid-19. 11 12 findings from the cleveland clinic foundation, a tertiary care referral centre, also show a consistent reduction in emergency transfers for stemi and other time-dependent emergencies coinciding with the covid-19 pandemic. 13 garcia et al analysed and quantified stemi activations for nine high volume cardiac catheterisation laboratories in the usa and found a 38% decrease in stemi activations of cardiac catheterisation laboratories across the us during the covid-19 period. 14 a recent international survey was conducted by the european society of cardiology (esc) looking at the perception of cardiology care providers with regards to stemi admissions to their hospitals. the investigators found a significant reduction in number of stemi admissions (>40%), an increase in presentations beyond the optimal window for ppci or thrombolysis (>40%). 1 the data from hong kong reported an increase in time taken for stemis to reach the hospital from 82.5 min to 318 min during the pandemic. 15 as a consequence of this latest trend of stemidelayed presentation, the number of mechanical and arrhythmogenic complications of stemi has seen a rise, which is a rare occurrence in the age of ppci. 16 it corresponds with our clinical experience with the forementioned patients who were reluctant to visit ed as they would have in normal circumstances. both of our patients had good family and social support, healthcare insurance to cover for medical expenses, but still evaded medical care for a time-dependent medical emergency. they belong to the cuyahoga county, one of the three largest counties of ohio, which has about 7400 hospital beds at 23 registered hospitals, 7427 physicians and 13 pci-capable healthcare facilities serving a population of approximately 12 million. 17 the decreased rate of hospital presentations for stemi has paralleled an increased incidence of patients presenting late after stemi onset. 18 physicians around the world are reporting severe complications of stemi from delayed presentations or lack of reperfusion 2 19-26 (table 3) . based on our review we hypothesise: 1. patients are not presenting to the hospital for medical emergencies 2. patients with angina symptoms and with/suspected/without covid-19 are presenting late to the hospital. delays in patients seeking medical care, delay in medical testing for suspected patients and delay due to severe covid-19 related symptoms are observed during the period of crisis. 2 19 20 physicians are observing worsening left ventricular functions, massive myocardial infarctions, life-threatening arrhythmias and cardiogenic shocks as complications of stemi, a rarity in the age of ppci. 2 19-26 it has translated into an increased mortality, prolonged admissions to the icu, a grave concern in these times of scarce resources. the observed phenomenon can be attributed to numerable patient and healthcare-related factors. 27 28 the establishment of covid-19 hospitals is making many patients reluctant to come to the hospital. patient 1 had concerns whether the cleveland clinic was transformed into a covid-19 hospital. such misconceptions and confusions along with alterations in patient behaviours of fear of contracting nosocomial covid-19 are a potential culprit. 2 moreover, patient 2 attempted to self-medicate herself with pantoprazole until her symptoms got severe. reduced family contact and supports during lockdown and the stress associated with stay-at-home orders are potential factors for delayed and decreased presentations for time-dependent medical emergencies. 19 low levels of exertion at home might not trigger cardiac symptoms and impaired manifestations of stemi related to neurotropic and neuroinvasive symptoms of covid-19 can play a role in those affected with the disease. 16 17 19 misinterpretation of stemi being relatively benign compared with covid-19 disease along with the fear of infection spread via hospitalised patients and healthcare workers is a common perception among community dwellers. 22 the covid-19 pandemic has put tremendous stress on the healthcare system across the world, even affecting countries with established medical resources. it has disrupted the established care pathways and work flow due to overwhelmed eds. there is a higher threshold of ed referrals by outpatient care providers, as observed with patient 2. healthcare personnel safety concerns are undeniable, especially with limited staffing resources from high healthcare worker infection rates. 27 the increasing trend of using fibrinolytic therapies to manage stemis in the ed, in an attempt to mitigate system-based delays, has also been described as a causative for re-emergence of rare complications. 26 there has been press releases from esc, american college of cardiology/american heart association, and healthcare experts have voiced concern in major newspapers for public awareness. [29] [30] [31] [32] [33] many patients, their families and their caregivers have come forward to share their experiences during this period of crisis. 33 34 on the media page of the cleveland clinic, global health cardiovascular experts have explained in simple terms the telltale signs of a heart attack as well as how delaying heart care in this covid-19 surge can lead to devastating consequences. 35 as the pandemic continues, it is imperative to commit stern steps of mass education and public awareness. 3 27 28 36 identification and correction of internal process delays is vital. the utilisation of telemedicine strategies, according to recent reports, was associated with improvement of stemi time of diagnosis and outcomes during the period of crisis. 37 further studies comparing telemedicine to the conventional way of managing patients with acs are need of the hour. altogether, these findings should be taken into serious consideration and effective plans drawn and implemented in case a second wave of the pandemic develops as lockdown restrictions are currently eased worldwide. twitter taha ahmed @tahaahmedmdccf acknowledgements we would like to acknowledge the significant contribution from dr emad dean nukta, who provided us with valuable inputs regarding the interventional management of the patients. we are grateful to both our patients for giving us permission to write up their cases. contributors ta: designed the study, performed the literature review, drafted the manuscript, formulated the tables and reviewed the manuscript. shl: performed the literature review, contributed to the discussion and suggested pertinent modifications. sk: contributed to the case presentation and discussion, revised the manuscript critically for important intellectual content and gave final approval for the version published. gvs: managed the cases, contributed to the case presentation and did a critical review and supervision. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer reviewed. this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. table 3 continued ► several community and healthcare-system-related factors delay and decrease the presentation and intervention for time-dependent non-communicable diseases such as stsegment elevation myocardial infarction (stemi) in the era of covid-19 crisis. ► as a consequence of these delays, healthcare providers should be vigilant in encountering and managing devastating complications of non-revascularised stemi, rarely encountered in the age of primary percutaneous coronary intervention. ► we present two intriguing cases of delayed presentation of stemi in the era of covid-19 pandemic with arrhythmogenic and mechanical complications, with a prolonged and arduous clinical course. ► this review focuses on several important patient and healthcare-system-related factors playing a vital role in this perplexing observation. ► several vital steps are postulated to halt this dangerous trend and assure the safety and well-being of general population in case a second wave of the pandemic develops. admission of patients with stemi since the outbreak of the covid-19 pandemic: a survey by the european society of cardiology collateral damage: medical care avoidance behavior amomg patients with myocardial infarction during the covid-19 pandemic be prepared how many hospital beds are near you? details by ohio county cuyahoga county reports most coronavirus deaths in the state esc guidelines for the management of acute myocardial infarction in patients presenting with st-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with st-segment elevation of the european society of cardiology (esc) stemi care during covid-19: losing sight of the forest for the trees where have the stemis gone during covid-19 lockdown? decline of acute coronary syndrome admissions in austria since the outbreak of covid-19: the pandemic response causes cardiac collateral damage impact of the covid-19 pandemic on healthcare activity in interventional cardiology in spain decrease in acute coronary syndrome presentations during the covid-19 pandemic in upstate new york stemi during the covid-19 pandemic -an evaluation of incidence impact of covid-19 pandemic on critical care transfers for st-segment-elevation myocardial infarction, stroke, and aortic emergencies reduction in st-segment elevation cardiac catheterization laboratory activations in the united states during covid-19 pandemic impact of coronavirus disease 2019 (covid-19) outbreak on st-segment-elevation myocardial infarction care in hong kong late stemi and nstemi patients' emergency calling in covid-19 outbreak ohio county profiles the covid-19 pandemic and cardiovascular complications what have we learned so far? st-segment elevation myocardial infarction in times of covid-19: back to the last century? a call for attention as the covid-19 pandemic drags on, where have all the stemis gone? late presentation of acute coronary syndrome during covid-19 delayed presentation of acute st segment elevation myocardial infarction complicated with heart failure in the period of covid-19 pandemic -case report delayed stemi presentation during the covid-19 pandemic post-mi ventricular septal defect during the covid-19 pandemic ventricular septal rupture complicating delayed acute myocardial infarction presentation during the covid-19 pandemic complication of late presenting stemi due to avoidance of medical care during the covid-19 pandemic eapci position statement on invasive management of acute coronary syndromes during the covid-19 pandemic acute coronary syndrome in the time of the covid-19 pandemic fear of covid-19 keeping more than half of heart attack patients away from hospitals coronavirus and your heart: don't ignore heart symptoms knocking down fears, myths and misinformation about calling 911 in the pandemic unusual stemi complications blamed on covid-19 hospital avoidance after man, 38, dies of heart attack, wife shares urgent message: go to the er. today health & wellness seek care for heart emergencies during covid-19 the obstacle course of reperfusion for stsegment-elevation myocardial infarction in the covid-19 pandemic telehealth strategy improves stemi care in latin america key: cord-355146-6rat5j64 authors: whittemore, paul; macfarlane, laura; herbert, anna; farrant, john title: use of awake proning to avoid invasive ventilation in a patient with severe covid-19 pneumonitis date: 2020-08-03 journal: bmj case rep doi: 10.1136/bcr-2020-236586 sha: doc_id: 355146 cord_uid: 6rat5j64 a 60-year-old man with swab-positive covid-19 and extensive ground-glass change seen on ct imaging was successfully managed on our covid-19 high-dependency unit with only low-flow oxygen and strict awake proning instructions. he was successfully weaned off oxygen entirely without any requirement for non-invasive or invasive ventilation and made a recovery to be discharged home after an 18-day hospital stay. a 60-year-old man with swab-positive covid-19 and extensive ground-glass change seen on ct imaging was successfully managed on our covid-19 highdependency unit with only low-flow oxygen and strict awake proning instructions. he was successfully weaned off oxygen entirely without any requirement for noninvasive or invasive ventilation and made a recovery to be discharged home after an 18-day hospital stay. the current covid-19 pandemic presents a considerable challenge to healthcare systems worldwide. given the nature and prevalence of this novel coronavirus, the issue of resource management (including ventilators and oxygen supplies) has become of paramount importance. in addition, there is a need to find ways to avoid intubation where possible as ventilated patients with covid-19 typically have poor outcomes when placed on mechanical ventilation. 1 we present a case of a 60-year-old man who developed extensive covid-19 pneumonitis who was successfully managed with low-flow oxygen (up to 12 l/min given via a non-rebreather mask) and awake proning and was able to be discharged home. this avoided the need for the higher oxygen flows associated with both non-invasive and invasive ventilations and the increased risks these treatments present to patients. a 60-year-old asian male non-smoker with no significant medical background presented to our accident and emergency (ae) department with significant and worsening shortness of breath. he had been self-isolating with covid-19 symptoms and was desaturating to spo 2 88% on arrival in ae. he initially required low flows of oxygen (<4 l) to maintain his saturations above 92%; arterial blood gases (abgs) on 35% oxygen revealed t1rf with ph 7.50, po 2 of 6.8 kp, pco 2 4.2, hco 3 26.6, base excess (be) 2.5 and lactate 2.2 . an initial chest x-ray (figure 1) showed extensive ground-glass changes to mid and lower zones in keeping with covid-19 infection. the following morning, the patient became more hypoxic and was randomised onto the recovery-rs (respiratory suport) trial, which has been designed to compare preintubation ventilation methods; the patient was randomised to usual care arm (low-flow oxygen) before being transferred to our combined covid-19 highdependency unit/ intensive care unit area. the patient tested swab-positive for covid-19 and was randomised onto the recovery trialdexamethasone 6 mg/day arm. given the patient's rising oxygen requirement and the growing evidence that there is a significant burden of pulmonary embolism in patients with covid-19, ct pulmonary angiography was performed (figure 2), which was negative for pulmonary embolus but did show severe extensive ground-glass change and septal thickening throughout both lungs. a bedside echocardiogram figure 1 chest x-ray on arrival. novel treatment (new drug/intervention; established drug/procedure in new situation) was performed to look for evidence of pulmonary hypertension. it showed normal left ventricular size and function. the right ventricle had a normal appearance with good function; importantly, it was not dilated, there was no discernible tricuspid regurgitation and the inferior vena cava was not dilated. we were therefore confident we could exclude pulmonary embolism as a cause of the patient's clinical deterioration. he remained on prophylactic enoxaparin. while on the unit, it became clear that the patient's oxygenation was much improved with prolonged periods of awake proning, generally in excess of 18 hours/day. when supine, there were recurrent desaturations as low as 82%, which we were able to correct to >94% simply by laying the patient in the prone position and not by making any alterations to oxygen delivery. the patient was managed entirely on low-flow oxygen (up to 12 l/min via a non-rebreather mask) for the entirety of his stay in the hospital. the patient remained conscious and lucid throughout his stay and successfully avoided the need for mechanical intervention as a result of strict proning instructions to which the patient adhered to, with the aim of treating the patient in the prone position for as much as possible, but ideally 18 hours/day. our unit has a dedicated 'proning team' made up of physiotherapists, mainly for proning intubated patients but who are also available to support awake proning through advice and assistance with movement. the patient did not require any sedation during this period. he was stepped down the respiratory ward before being successfully weaned off supplementary oxygen with a resting o 2 saturation of 95% at discharge. proning is a recognised tool for improving gas exchange in mechanically ventilated patients with acute lung injury/acute respiratory distress syndrome and helps to improve ventilation distribution towards non-dependent lung regions and causes a redistribution of lung perfusion. 2 our case study highlights the potential for the use of awake proning in those patients who are not intubated, both as an adjunct to treatment with oxygen therapy and non-invasive ventilation. in a recent pilot of awake proning in patients with covid-19 at one new york emergency department, the median spo 2 improved from 84% to 94%. 3 ongoing resource limitation is likely to be a feature of the global healthcare response to the covid-19 pandemic, and awake proning has the potential to significantly reduce the amount of oxygen required to treat selected patients, even in those with severe parenchymal disease, as demonstrated. in addition to this awake proning may negate the need for mechanical ventilation and level 3 care. with the outcome in mechanically ventilated patients being poor, awake proning may also prove useful in those patients with limitations to their care due to comorbidity. once the pandemic has abated, there may be a role for awake proning in patients with other respiratory illness/infection who are proving difficult to oxygenate in the more conventional supine position, though further studies are required to validate it as an effective treatment. ► awake proning simply involves treating patients in the prone position and can significantly improve oxygenation in patients with covid-19 pneumonitis. ► this method may avoid the need for patients to undergo risky and resource-intensive mechanical ventilation. ► awake proning can form part of an integrated pathway for covid-19 management to use resources in the most efficient way possible. contributors pw: planning of report, conduct of the study, reporting, acquisition of data and analysis; jf: planning of report, conduct of the study, acquisition of data and analysis; lm: planning and conduct of the study; ah: planning and conduct of the study. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with covid-19 in the new york city area pathophysiology of prone positioning in the healthy lung and in ali/ards early self-proning in awake, non-intubated patients in the emergency department: a single ed's experience during the covid-19 pandemic competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. paul whittemore http:// orcid. org/ 0000-0001-8605-041x key: cord-338689-4u1ezk64 authors: ata, fateen; almasri, hussam; sajid, jamal; yousaf, zohaib title: covid-19 presenting with diarrhoea and hyponatraemia date: 2020-06-07 journal: bmj case rep doi: 10.1136/bcr-2020-235456 sha: doc_id: 338689 cord_uid: 4u1ezk64 covid-19 is a viral disease with a high infectivity rate. the full spectrum of the disease is not yet understood. this understanding may help in limiting potential exposure. we present a young man with diarrhoea, abdominal pain and hyponatraemia who turned out to be positive for covid-19. covid-19 is a viral disease with a high infectivity rate. the full spectrum of the disease is not yet understood. this understanding may help in limiting potential exposure. we present a young man with diarrhoea, abdominal pain and hyponatraemia who turned out to be positive for covid-19. covid-19 is caused by the novel severe acute respiratory syndrome coronavirus 2 (sars-cov-2). fever is a common presenting symptom, along with cough, dyspnoea, myalgia and fatigue. severe cases may lead to organ dysfunction and death. 1 as with any infectious disease, one of the challenges with covid-19 is to understand both the typical and atypical disease presentations. atypical presentations carry the risk of going undetected for a longer duration, and in turn may lead to the spillover of the disease in a healthcare setting as well as the community. a 27-year-old indian man, with known type 2 diabetes, presented with a 5-day history of gradually progressive, moderate severity, generalised abdominal pain. the pain was accompanied by watery diarrhoea five to six times per day. he did not have any fever, sore throat, myalgias, influenzalike symptoms or shortness of breath. a review of systems was remarkable for dry cough of similar duration. there was no recent history of travel and no sick contacts or animal exposure. on initial presentation, he was not febrile, tachypnoeic, tachycardiac or hypotensive. physical examination revealed a patient in distress due to abdominal pain. there was mild generalised abdominal tenderness, but no guarding, rigidity or rebound. the chest examination showed coarse bibasal crackles. the rest of the physical examination was unremarkable. initial work-up revealed normocytic anaemia, thrombocytopaenia and non-elevated inflammatory markers. two repeated samples confirmed asymptomatic hyponatraemia. liver enzymes, renal function and the endocrine panel were unremarkable. syndrome of inappropriate antidiuretic hormone secretion (siadh) was the probable cause of hyponatraemia (table 1) . on the first day of admission, the patient developed high-grade fever. he was placed under isolation and screened for viral respiratory infections. the patient turned out to be positive for covid-19. given the patient's chief complaint of abdominal pain with diarrhoea, gastroenteritis was the initial working diagnosis. there was no food intake from outside and no sick contacts. stool analysis for ova and parasites was negative. also, elisa immunoassay for clostridium difficile toxin came out negative. stool culture was unrevealing. stool pcr for sars-cov-2 was unavailable in the local hospital lab. pancreatitis was another differential, but lipase was negative. atypical pneumonia was another possibility considering the minimal respiratory symptoms and bilateral chest x-ray findings (figure 1). the patient did not produce any sputum for culture, and two sets of blood cultures were negative. due to hyponatraemia, legionella pneumonia was considered; however, the urinary antigen was negative. viral pneumonia was another diagnostic possibility for which a viral panel was sent, which included sars-cov-2 pcr, which eventually came back positive and hence confirmed the diagnosis of the novel coronavirus pneumonia (table 2) . the patient was initially started on ceftriaxone, azithromycin and oseltamivir as empirical therapy for community-acquired pneumonia. after the tests for covid-19 pcr from nasal swab came positive, the patient received chloroquine phosphate 250 mg two times per day, darunavir/cobicistat 950 mg daily and ribavirin 1200 mg two times per day for 14 days, based on local guidelines. ribavirin 1200 mg two times per day was added to his antiviral regimen. the patient remained clinically stable throughout the hospital course until discharge. the patient's abdominal pain and diarrhoea resolved without any specific management. he did not require any ventilatory support during his stay. his sars-cov-2 pcr turned negative on repeat testing after 2 weeks and he was discharged home. learning points ► knowing the atypical presentation of the disease is as important as knowing a typical presentation. ► anyone with gastrointestinal symptoms with no alternative explanation should be isolated and screened for covid-19. ► early screening may impact the spread of the disease. ► we recommend studies to evaluate the effectiveness of stool pcr for severe acute respiratory syndrome coronavirus 2 if initial nasopharyngeal pcr is negative and suspicion remains high. the novel coronavirus belongs to a group of severe acute respiratory syndrome-related coronaviruses. 2 it originated in wuhan, hubei province, china, in december 2019 and was declared a pandemic by who on 11 march 2020. 3 the most common clinical features are fever, dry cough, myalgia, anorexia and dyspnoea. 4 gastrointestinal symptoms such as diarrhoea, abdominal pain and vomiting have been previously seen with acute viral respiratory infections and reported recently as rare manifestations of covid-19. [4] [5] [6] the confirmation of a suspected case relies on sars-cov-2 rna detection via pcr. watery diarrhoea is present in sars-cov-1 infection secondary to virus replication within the intestinal cells. 7 the presence of gastrointestinal symptoms in coronavirus infection (sars-cov-1 and sars-cov-2) can be linked to the distribution of ace2 receptor, which is present in lung alveolar type 2 cells, as well as in enterocytes. 8 acute hyponatraemia is present in atypical pneumonia, especially legionella. 9 the underlying mechanism is the syndrome of inappropriate antidiuretic hormone (adh) secretion. 10 there is a rapidly accumulating body of knowledge regarding the epidemiology, pathophysiology, clinical manifestations, infection control and management of covid-19. like any other rna virus, sars-cov-2 attacks the host cell, and penetrates and enters the nucleus for replication. the virus has an affinity to ace2 as binding receptors. 11 this affinity is the probable reason that the lungs are the most commonly affected organs. the response of the host organ can be from minimal symptoms to organ failure. t cell immune response to the coronaviruses has been studied in the past. 12 another common disease phenomenon observed and reported is a hypercoagulable state, which can be explained by the expression of ace2 enzymes by the endothelium. 13 similarly, the gastrointestinal tract also expresses ace2, leading to a viral attack of the system. 14 there is ongoing research to understand the pathophysiology of covid-19 infection. an important aspect is to understand the atypical presentation of the disease. timely detection of suspected cases with prompt isolation and screening is one of the factors that may help curb the spread in the community. 15 our patient had acute hyponatraemia, abdominal pain and diarrhoea with minimal clinical course and risk factors for mortality of adult inpatients with covid-19 in wuhan, china: a retrospective cohort study the species severe acute respiratory syndromerelated coronavirus: classifying 2019-ncov and naming it sars-cov-2 who director-general's opening remarks at the media briefing on covid-19 -11 clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in wuhan, china clinical and virological factors associated with gastrointestinal symptoms in patients with acute respiratory infection: a two-year prospective study in general practice medicine clinical features of patients infected with 2019 novel coronavirus in wuhan a novel coronavirus associated with severe acute respiratory syndrome covid-19: gastrointestinal manifestations and potential fecaloral transmission legionnaires' disease hyponatraemia and the inappropriate adh syndrome in pneumonia covid-19 pathophysiology: a review t cell-mediated immune response to respiratory coronaviruses angiotensin converting enzyme-2 confers endothelial protection and attenuates atherosclerosis the digestive system is a potential route of 2019-ncov infection: a bioinformatics analysis based on single-cell transcriptomes the international bank for reconstruction and development / the world bank competing interests none declared. patient consent for publication obtained.provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. fateen ata http:// orcid. org/ 0000-0001-7121-8574 hussam almasri http:// orcid. org/ 0000-0002-9549-8352 zohaib yousaf http:// orcid. org/ 0000-0002-4631-9899 key: cord-346246-2phtdgh4 authors: mattar, shaikh abdul matin; koh, samuel ji quan; rama chandran, suresh; cherng, benjamin pei zhi title: subacute thyroiditis associated with covid-19 date: 2020-08-25 journal: bmj case rep doi: 10.1136/bcr-2020-237336 sha: doc_id: 346246 cord_uid: 2phtdgh4 we report a case of a hospitalised patient with covid-19 who developed subacute thyroiditis in association with sars-cov-2 infection. the patient presented with tachycardia, anterior neck pain and thyroid function tests revealing hyperthyroidism together with consistent ultrasonographic evidence suggesting subacute thyroiditis. treatment with corticosteroids resulted in rapid clinical resolution. this case illustrates that subacute thyroiditis associated with viruses such as sars-cov-2 should be recognised as a complication of covid-19 and considered as a differential diagnosis when infected patients present with tachycardia without evidence of progression of covid-19 illness. as of 1 may 2020, 17101 people with covid-19 have been diagnosed in singapore with migrant workers residing in dormitories forming the majority (n=14 776, 86.4%). 1 we report a unique case of a migrant worker from myanmar who developed subacute thyroiditis in association with covid-19, which is the first case reported in asia to our knowledge. on day 10 of illness, he developed anterior neck pain and sinus tachycardia with thyroid function tests revealing primary hyperthyroidism. ultrasonography of his thyroid gland was consistent with subacute thyroiditis and he was administered oral corticosteroids, resulting in rapid clinical improvement. this case highlights the importance of good history taking and awareness of the diagnosis of thyroiditis in order to elicit the finding of anterior neck pain that can be conflated with upper respiratory tract symptoms in a persistently tachycardic patient with covid-19. a 34-year-old man from myanmar with no medical history or known covid-19 exposure presented to the emergency department at singapore general hospital with a 4-day history of fever, dry cough, headache and anosmia. on admission, he had a temperature of 37.7°c, blood pressure of 120/90 mm hg, heart rate of 89 beats/min, respiratory rate of 19 breaths/min and an oxygen saturation (spo 2 ) of 96% on room air. auscultation of the lungs was clear with no adventitious sounds. given the clinical features and risk factors, an oropharyngeal swab and testing for covid-19 was performed using reverse transcription real-time qualitative pcr on the roche cobas 6800 system using roche cobas sars-cov-2 test. the test for sars-cov-2 was positive. initial laboratory tests on admission to the hospital showed a normal white cell count (9.8×10 9 /l), haemoglobin level (14.3 g/dl) and platelet count (444 000/mm 3 ). c reactive protein (crp) level was mildly elevated at 11.3 mg/l, and lactate dehydrogenase (ldh) was within normal limits at 433 units/l. a chest x-ray (cxr) performed reported no pulmonary consolidation or pleural effusion. he was admitted to an isolation cohort ward for further management of covid-19 upper respiratory tract infection (urti) with consideration to transfer to a community isolation facility should he continue to remain stable without any progression of covid-19. on the third day of admission, the patient complained of ongoing dry cough associated with sore throat. vital signs remained stable and he remained afebrile. symptomatic treatment with paracetamol and dequalinium lozenges were given. however, from the fifth day of the hospital stay (day 9 of illness), he had new complaints of an anterior neck pain with a score 5/10 that was refractory to symptomatic treatment and a new onset of tachycardia ranging from 90 to 120 beats/ min. he remained afebrile with spo 2 >96% on room air. his oropharynx was not injected nor had any exudates. auscultation of the lungs revealed no adventitious sounds. on examination of his neck, a diffuse asymmetric goitre was found with regions on both lobes that were hard and tender to palpation. there was no retrosternal extension or palpable bruit. few cervical lymph nodes were palpable bilaterally. he did not have any eye signs of thyrotoxicosis or thyroid eye disease, pretibial myxoedema or hand tremors. additionally, examination of his skin revealed no exanthem. further relevant history to his thyroid status revealed no palpitations, diarrhoea, increased appetite, unintentional weight loss or heat intolerance on presentation or preceding this admission. he did not have history of thyroid disease in the past but had a positive family history for thyroid disease. in view of tachycardia and a tender goitre found, a thyroid function test was done revealing primary hyperthyroidism with elevated free thyroxine 3 (13.4 pmol/l), free thyroxine 4 (41.8 pmol/l) and suppressed thyroid-stimulating hormone (tsh) (<0.01 mu/l). thyrotropin receptor antibody new disease (trab) and thyroperoxidase antibody (tpoab) were negative. notably, crp was also markedly elevated to 122 mg/l, while procalcitonin remained unremarkable (0.13 µg/l). alkaline phosphatase was also mildly elevated (218 u/l) without hyperbilirubinaemia. the ecg corresponding to the tachycardia episodes revealed a sinus tachycardia rhythm with no evidence of atrial fibrillation. a cxr that was repeated did not reveal any new pulmonary consolidation. a summary of investigations on admission and during the onset of tachycardia can be seen in table 1. ultrasound of the neck (figure 1) showed an enlarged thyroid gland with heterogenous echotexture. both lobes had hypoechoic areas with ill-defined margins corresponding to the hard regions palpable. colour flow doppler showed reduced blood flow in both lobes. there were no definite nodules seen in the thyroid gland. a few cervical lymph nodes with normal morphology were seen. subacute thyroiditis is fundamentally a clinical diagnosis, and our patient presented with clinical manifestations that were sufficient to establish this as a leading differential diagnosis, given the new-onset neck pain, thyroid tenderness and a diffuse asymmetric goitre in the context of a preceding upper respiratory tract viral illness and hyperthyroidism. the classical ultrasound finding of hypoechoic and heterogenous enlarged thyroid gland with reduced blood flow was also supportive of the diagnosis. furthermore, trab and tpoab were negative, rendering the diagnoses of grave's disease and autoimmune thyroiditis unlikely. investigations also did not support an acute infectious thyroiditis of a 'suppurative' type with normal procalcitonin levels and blood cultures that did not grow any bacteria after 48 hours in incubation. further results of tests performed to exclude other common viral infective causes of thyroiditis were normal. notably, a throat swab sent for a respiratory virus multiplex pcr was negative for influenza a and b, adenovirus and human enterovirus. measles, mumps and rubella virus serologies suggested immunity. hence, sars-cov-2 was the likely viral trigger of the subacute thyroiditis in this particular case. in view of the significant pain and discomfort and hyperthyroidism with tachycardia, he was commenced on prednisolone at a dose of 20 mg. a steroid-tapering regimen was planned for him to decrease the dosage of prednisone to the minimum required for symptomatic relief with periodic monitoring of thyroid function. beta-blocker treatment was also initiated with atenolol at a dosage of 25 mg every morning. two days after starting oral steroid treatment, the anterior neck pain had substantially reduced to a pain score of 2/10 from 5/10. the palpable hard swellings on either lobe of the thyroid gland that were found at diagnosis had rapidly disappeared after treatment, which supports the diagnosis of subacute thyroiditis. on day 5 of treatment, the crp level was noted to be downtrending markedly from 122 mg/l, which was documented on the diagnosis of thyroiditis to a much lower level of 16.5 mg/l. there was clinical commensuration with the downtrending inflammatory markers as the tachycardia had resolved with the neck pain. he subsequently continued to remain well with supportive management for urti symptoms and was discharged for follow-up with an endocrinologist after recovery from covid-19. he was reviewed after 10 weeks in the outpatient clinic. he had completed his tapering course of steroids and was clinically well with no symptoms. his thyroid function tests normalised with an ft4 level of 11.0 pmol/l and a tsh level of 2.10 mu/l. the thyroid gland was normal to palpation with no palpable cervical lymph nodes. his steroid therapy was stopped in view of complete resolution of his symptoms with a scheduled early follow-up. we report the first case of subacute thyroiditis in an asian population where the temporal sequence and the exclusion of other viral infections suggest covid-19 as the causal factor. the importance of detailed history taking and physical examination of the neck is illustrated by our case. capturing the distinctive history of neck pain which can often be conflated with symptoms of pharyngitis, a very common complaint in covid-19 urti, was key to the spearhead the clinical reasoning process that led to the diagnosis. subacute thyroiditis is presumed to be caused by a viral infection or a postviral inflammatory process with clusters of disease reported during outbreaks of viral infections drawing much parallel to that of the current covid-19 pandemic situation. this further highlights the importance for physicians to be vigilant of the diagnosis while treating patients with covid-19 who may have multiple upper respiratory symptoms. reviews of literature have shown that evidence for viral infection in subacute thyroiditis was linked to mumps virus, coxsackievirus, adenovirus, epstein-barr virus, rubella and cytomegalovirus, though a specific viral cause is not always found. 2 in our case of a mild covid-19 urti, there was sufficient clinical and virological evidence within reasonable limits that failed to yield any other alternative viral trigger other than sars-cov-2. from a pathophysiological standpoint, previous studies examining the pathology of the thyroid in severe acute respiratory syndrome proposed several mechanisms of thyroid organ damage that include host immune overreaction, immune deficiency related to infection, destruction of lymphocytes, inhibition of the innate immune response and direct cellular destruction with apoptosis playing a key role. 3 much as been discussed about ace2, which is key to the mechanism of sars-cov-2 infection with the virus using it as a host cell receptor to invade human cells. more recent studies based on sars-cov-2 in 2020 have shown that ace2 expression levels were highest in thyroid among other organs, such as the small intestine, kidneys, heart and adipose tissue, which does give insight into a plausible mechanism for pathophysiology of thyroiditis in covid-19 . 4 5 we acknowledge similar cases reported in an 18-year-old woman in italy and also in a middle-aged caucasian woman in turkey. 6 7 given prior described literature by ohsako et al on genetic aspects of subacute thyroiditis and certain human leucocyte antigens that predispose to subacute thyroiditis in a japanese study, 8 our case further sheds light onto possible research directions into gender, ethnic and therefore genetic predilection of viral subacute thyroiditis in the different populations demonstrated in reports so far. in a hospitalised patient for mild to moderate covid-19, a presentation of sinus tachycardia may lead to a differential diagnosis of worsening sepsis or progression of covid-19 illness, which we agree should be dutifully ruled out as illustrated in our case report. our case highlights the importance of being cognisant of the wide differentials in a patient with covid-19 who develops tachycardia, such as cardiac, pulmonary, haematological and also thyroid dysfunctions, which eventually surfaced in our case. in an outbreak setting, we also note to consider physical deconditioning and anxiety as other causes of persistent unexplained tachycardia in the daytime, which has been described in prior cohort studies of sars patients in 2004. 9 in summary, thyroiditis and resultant thyrotoxicosis should always be considered as a differential in patients with covid-19. though we acknowledge the wide array of differentials of tachycardia in a hospitalised patient with covid-19, the eventual recognition of clinical, biochemical and radiological findings led to the diagnosis of a viral thyroiditis that was amenable to inexpensive treatment and rewarding outcomes of rapid symptom relief. furthermore, the importance of clinically recognising thyroiditis transcends all levels of medical care from tertiary care providers in hospitals to primary care physicians holding the fort in the community for well and stable cases for which thyroiditis may present as a delayed complication of covid-19. ► covid-19 is a novel disease for which its clinical presentation, potential complications and organ involvement are still being elucidated in literature. ► anterior neck pain, which can be conflated with upper respiratory tract symptoms especially in the setting of covid-19, should not be dismissed and warrants further examination and investigation as required. ► subacute thyroiditis is a rare complication of covid-19 that should be considered especially in the setting of persistent tachycardia without any suggestion of progression of covid-19 and other common cardiorespiratory causes. this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. shaikh abdul matin mattar http:// orcid. org/ 0000-0002-1184-4263 updates on covid-19 (coronavirus disease 2019) local situation. ministry of health viruses and thyroiditis: an update pathology of the thyroid in severe acute respiratory syndrome expression of the sars-cov-2 cell receptor gene ace2 in a wide variety of human tissues the human protein atlas -tissue expression of ace2 subacute thyroiditis after sars-cov-2 infection a case of subacute thyroiditis associated with covid-19 infection clinical characteristics of subacute thyroiditis classified according to human leukocyte antigen typing tachycardia amongst subjects recovering from severe acute respiratory syndrome (sars) key: cord-346345-jc9bq0zu authors: smith, colin m; komisar, jonathan r; mourad, ahmad; kincaid, brian r title: covid-19-associated brief psychotic disorder date: 2020-08-11 journal: bmj case rep doi: 10.1136/bcr-2020-236940 sha: doc_id: 346345 cord_uid: jc9bq0zu a 36-year-old previously healthy woman with no personal or family history of mental illness presented with new-onset psychosis after a diagnosis of symptomatic covid-19. her psychotic symptoms initially improved with antipsychotics and benzodiazepines and further improved with resolution of covid-19 symptoms. this is the first case of covid-19-associated psychosis in a patient with no personal or family history of a severe mood or psychotic disorder presenting with symptomatic covid-19, highlighting the need for vigilant monitoring of neuropsychiatric symptoms in these individuals. a 36-year-old previously healthy woman with no personal or family history of mental illness presented with new-onset psychosis after a diagnosis of symptomatic covid-19. her psychotic symptoms initially improved with antipsychotics and benzodiazepines and further improved with resolution of covid-19 symptoms. this is the first case of covid-19associated psychosis in a patient with no personal or family history of a severe mood or psychotic disorder presenting with symptomatic covid-19, highlighting the need for vigilant monitoring of neuropsychiatric symptoms in these individuals. the novel coronavirus (severe acute respiratory syndrome coronavirus 2; sars-cov-2), the causative agent of the covid-19, is rapidly emerging. from 29 december 2019, when the first cases of covid-19 were documented in wuhan, china, covid-19 has resulted in more than 3.9 million infections in the usa, representing nearly 30% of cases worldwide. 1 2 typical symptoms of covid-19 are dyspnoea, cough, fever, myalgia and sore throat, though nervous system involvement, resulting in cerebrovascular diseases, encephalopathy, encephalitis and new-onset anosmia and dysgeusia, has been documented. [3] [4] [5] recent cases of reactive psychosis in the context of the covid-19 pandemic have emerged in the literature, but less attention has been given to incident psychosis affecting patients with covid-19. 6 although a recent report documented cases of covid-19-related psychosis in madrid, this did not include a clinical description of affected patients. 7 ferrando et al 8 described three cases of new-onset psychosis in patients with asymptomatic covid-19, though two of these patients had a pre-existing psychiatric illness, and there were concerns for concurrent delirium. here, we report a case of symptomatic covid-19-related psychosis in a patient with no personal or family history of mental illness and briefly discuss the relevant literature on coronavirus-associated psychosis. a 36-year-old african-american woman employed at a skilled nursing facility with a remote history of erythema multiforme, and no psychiatric history, was diagnosed with covid-19 by nasopharyngeal swab after a known exposure at work. symptoms at the time of diagnosis with covid-19 were notable for rhinorrhoea and nasal congestion without any concomitant dyspnoea or documentation of anosmia or dysgeusia. approximately 4 days following onset of upper respiratory symptoms, she was noted to have an acute, rapidly progressive change in her behaviour characterised by prominent persecutory delusions and decreased sleep. her delusions were primarily directed at her partner and focused on the safety of her children and personal finances. she believed her partner was attempting to kidnap her children and steal her covid-19 stimulus money. collateral information from the patient's family revealed that she had been engaging in ruminative, persecutory thought patterns centring around being 'tracked by cell phones' in the days preceding hospitalisation. this began after a domestic dispute with her partner. her symptoms culminated in the patient attempting to pass her children through a local fast-food restaurant drive-through in an effort to prevent their kidnapping, at which time first responders were notified and she was transported to the hospital. due to the acute onset of psychosis of unclear aetiology and her positive covid-19 status, the patient was initially admitted to the general medicine service, whereupon psychiatry was consulted for further evaluation and management. at the time of her initial psychiatric interview, she was avoiding eye contact, but had no psychomotor agitation or retardation. she did not appear to be responding to internal stimuli. her speech was noted to be increased in rate, though interruptible with repeated prompts. she described her mood as 'worried', and her affect was congruent to mood. she exhibited a tangential thought process with content notable for persecutory delusions. at the time of initial assessment she denied any suicidality or homicidality. attention, concentration and orientation were intact on bedside testing. vital signs on admission were: temperature 36.8°c, heart rate 79 beats per minute, respiratory rate 19 breaths per minute and blood pressure 114/85 mm hg. laboratory testing revealed positive sars-cov-2 nasopharyngeal swab, mild leucocytosis (white cell count 11.5×10 9 /l, 86.4% neutrophils), elevated c-reactive protein (2.37 mg/dl), elevated d-dimer (2274 ng/ml fibrinogen equivalent units), but otherwise normal electrolytes, ferritin, renal function, urine analysis and toxicology. interleukin levels were not measured as it was not part of the standard of care at our institution. ct scan and mri of the head were normal. a lumbar puncture revealed: cerebrospinal fluid colour was colourless, hazy, red cell count 187×10 12 /l, and nucleated cell count 1/μl in tube 1, glucose 69 mg/dl and protein 20 mg/dl. extended meningitis pcr panel was negative. given the paucity of alternative aetiologies for her development of acute psychosis, it was felt that the unusual association of diseases/symptoms patient's symptoms were either representative of a first-episode psychosis, triggered by psychosocial stressors secondary to her recent covid-19 diagnosis, a brief psychotic disorder in the setting of an obvious stressor, or a direct sequela of covid-19 infection and representative of a brief psychotic disorder. delirium was also considered, but she lacked alterations in attention or awareness on bedside evaluation and did not screen positive using our institution's nursing delirium observation scale. due to the severity of the patient's psychiatric symptoms, inability to engage in reality testing and perceived elevated risk of both harm to self and others (as her acute illness limited her ability to engage in and appreciate the need for social isolation as an active carrier of covid-19), the patient was initially involuntarily committed, and pharmacotherapy was initiated. she was initially treated with two daily doses of olanzapine 2.5 and 5 mg in an effort to target both her underlying psychotic symptoms and aid in sedation to promote restoration of the patient's sleep-wake cycle. despite initiation of olanzapine, the patient remained paranoid with prominent delusional thinking and minimal insight, leading to an episode of acute agitation. given the severity of her ongoing symptoms, clonazepam 0.5 mg twice daily was added for acute anxiolysis and reduced to once daily. considering the possibility that she would need to be on antipsychotics at discharge, and that olanzapine is not recommended as first-line therapy in psychosis (due to metabolic side effects) she was transitioned to risperidone. with titration to 3 mg of risperidone daily, the patient had significant improvement in her persecutory delusions and subsequently exhibited improvement in her insight and judgement. clonazepam was discontinued and she was discharged on hospital day 7 on risperidone 3 mg nightly with a plan for close outpatient follow-up with psychiatry. of note, she did not require any therapy for her covid-19 infection as she remained on room air after hospitalisation with resolution of her respiratory symptoms. follow-up documentation from her outpatient provider 1 week after discharge noted that she had not attended her psychiatry intake appointment, though she had noted near resolution of her psychiatric symptoms and had self-discontinued the risperidone without return of her persecutory delusions. to our knowledge, this case represents the first description of symptomatic covid-19-associated brief psychotic disorder in an individual with no personal or family history of primary psychiatric illness. a case series in madrid noted an unspecified number of potential cases of covid-19-related psychosis in their hospital, but did not detail the clinical course of affected patients. 7 a recent case series in new york described three cases of new-onset psychosis in patients with covid-19. 8 however, all patients were incidentally found to have positive sars-cov-2 test and did not present with other symptoms to suggest infection, calling into question whether the diagnosis of covid-19 was related to the psychosis. further, one patient had a comorbid panic disorder, which may lead to heightened vulnerability to psychotic illness, and another was experiencing homelessness and was on 120 mg of methadone for opioid use disorder, again confounding the diagnosis of covid-19 psychosis. 9 in the case presented herein, there was no history of prodromal symptoms, no personal or family history of mental illness and a relatively rapid resolution of psychosis. further, she did not have a history of substance use or propsychotic medication (such as steroids) use, and the onset of psychosis coincided with upper respiratory symptoms. given the temporality between infection and psychiatric symptoms, along with the resolution of symptoms with improvement of covid-19-related symptoms, a working diagnosis of brief psychotic disorder associated with covid-19 was given. 10 the mechanism by which covid-19 may have precipitated psychosis in this patient is not entirely clear, but could be related to the diagnosis of covid-19, increased stress in the setting of ongoing infection or a viral mediated psychosis. indeed, respiratory viruses have been associated with psychosis since the 1918 influenza pandemic when menninger published a report of 100 patients with neuropsychiatric sequelae associated with influenza infection, including 25 with 'dementia praecox' and 23 with 'other psychoses'. 11 12 coronaviruses, too, have been linked to psychosis. a recent rapid review of epidemic and pandemic literature identified five papers (four observational studies and one case series) reporting incident psychosis in sars and one paper reporting psychosis in middle east respiratory syndrome. [13] [14] [15] [16] [17] [18] [19] the incident rate of psychotic symptoms across observational studies was between 0.9% and 11.8%. 14-16 19 sars-related psychotic symptoms were associated with higher doses of corticosteroids, severity of sars symptoms and family history of psychiatric illness and psychosocial stressors. 14 15 the single case series of three patients with sarsrelated psychosis suggested that sars severity, steroid treatment and social isolation were contributing factors. 18 severance et al 17 reported an association between coronaviruses and psychotic symptoms by measuring immunoglobulin g (igg) response against four human coronavirus strains in patients with recent onset of psychotic illness compared with healthy controls. the authors found that patient igg levels for two strains of coronavirus (hku1 and nl63) were significantly higher in patients with psychotic symptoms when compared with controls, suggesting these two coronaviruses may be risk factors for neuropsychiatric illness. although heightened stress of a covid-19 diagnosis or medications (such as corticosteroids) may unmask an underlying primary psychotic disorder in a vulnerable individual, the idea that sars-cov-2 may itself trigger psychosis through direct neurotoxicity or a heightened immune response is not unreasonable. 13 coronaviruses are neurotropic, for example, and sars-cov-2 rna has recently been isolated from the central nervous system of a patient. 4 20 moreover, the antipsychotics haloperidol and chlorpromazine have displayed antiviral activity against sars-cov-2 in vitro and in a mice model, respectively. 21 22 in a review of the literature, troyer et al 23 offer direct infection, blood circulation, neuronal involvement, hypoxic injury, immune injury and ace2 binding as possible culprits of coronavirus nervous system damage. with these data in mind, we contend that a relevant neuropsychiatric review of systems and full exam should be completed in patients presenting with suspected or confirmed covid-19. newonset psychosis in a patient with suspected or confirmed covid-19, without personal or family history of mental illness and no other clear precipitant, should prompt further medical workup (eg, head imaging and lumbar puncture). this is consistent with the the american psychiatric association's draft 2019 guidelines for schizophrenia treatment, which state that clinicians should be alert to features that suggest a need for additional physical or laboratory evaluation in first-episode psychosis. 24 although studies investigating the treatment of covid-19 psychosis have not been undertaken, treatment of secondary psychosis should be geared towards treating the underlying illness while managing psychotic symptoms with antipsychotics and benzodiazepines at the lowest possible dose. 25 given concerns for dysrhythmias in patients with pre-existing cardiac injury and covid-19, intravenous haloperidol should be avoided in this population, where possible. 26 a novel coronavirus from patients with pneumonia in china coronavirus covid-19 global cases by the center for systems science and engineering johns hopkins university coronavirus resource center website clinical characteristics of coronavirus disease 2019 in china a first case of meningitis/encephalitis associated with sars-coronavirus-2 neurologic manifestations of hospitalized patients with coronavirus disease reactive psychoses in the context of the covid-19 pandemic: clinical perspectives from a case series new-onset psychosis in covid-19 pandemic: a case series in madrid covid-19 psychosis: a potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response? panic attacks with psychotic features secondary psychoses: an update schizophrenia and influenza at the centenary of the 1918-1919 spanish influenza pandemic: mechanisms of psychosis risk psychoses associated with influenza: i. general data: statistical analysis mood and cognitive changes during systemic corticosteroid therapy the effects of disease severity, use of corticosteroids and social factors on neuropsychiatric complaints in severe acute respiratory syndrome (sars) patients at acute and convalescent phases factors associated with psychosis among patients with severe acute respiratory syndrome: a case-control study long-term psychiatric morbidities among sars survivors coronavirus immunoreactivity in individuals with a recent onset of psychotic symptoms psychiatric complications in patients with severe acute respiratory syndrome (sars) during the acute treatment phase: a series of 10 cases psychiatric findings in suspected and confirmed middle east respiratory syndrome patients quarantined in hospital: a retrospective chart analysis neuroinvasion by human respiratory coronaviruses a sars-cov-2 protein interaction map reveals targets for drug repurposing broad anti-coronaviral activity of fda approved drugs against sars-cov-2 in vitro and sars-cov in vivo are we facing a crashing wave of neuropsychiatric sequelae of covid-19? neuropsychiatric symptoms and potential immunologic mechanisms practice guideline for the treatment of patients with schizophrenia the psychopharmacology of agitation: consensus statement of the american association for emergency psychiatry project beta psychopharmacology workgroup clinical features of patients infected with 2019 novel coronavirus in wuhan, china acknowledgements we appreciate lisa vann, md and kristen shirey, md for their clinical guidance in the care of this patient. ► individuals with covid-19 may be at risk of developing neuropsychiatric symptoms, including psychosis. ► covid-19 diagnosis could predispose vulnerable patients to psychosis and clinicians should be aware of this. ► a diagnosis of covid-19 should prompt a neuropsychiatric review of systems and psychiatric exam. ► in individuals presenting with new-onset psychosis in areas endemic to covid-19, consideration should be made for testing in the absence of respiratory symptoms.copyright 2020 bmj publishing group. all rights reserved. for permission to reuse any of this content visit https://www.bmj.com/company/products-services/rights-and-licensing/permissions/ bmj case report fellows may re-use this article for personal use and teaching without any further permission.become a fellow of bmj case reports today and you can: ► submit as many cases as you like ► enjoy fast sympathetic peer review and rapid publication of accepted articles ► access all the published articles ► re-use any of the published material for personal use and teaching without further permission if you have any further queries about your subscription, please contact our customer services team on +44 (0) 207111 1105 or via email at support@bmj.com.visit casereports.bmj.com for more articles like this and to become a fellow key: cord-341948-9w8od50e authors: scott, michael; helmy, ahmed hazem title: rare encounter: hydrocoele of canal of nuck in a scottish rural hospital during the covid-19 pandemic date: 2020-08-11 journal: bmj case rep doi: 10.1136/bcr-2020-237169 sha: doc_id: 341948 cord_uid: 9w8od50e we report the case of a 32-year-old woman who presented with reducible indirect inguinal hernia and a challenging constellation of symptoms, signs and radiographic findings. surgical approach superseded conservative management when the patient’s abdomen became acute, with a rising lactate and haemodynamic instability. specifically, the presence of a fluid collection was concerning for sinister acute pathology. our patient was rediagnosed intraoperatively with hydrocoele of canal of nuck. this so-called ‘female hydrocoele’ is an eponymous anatomical rarity in general surgery, presenting as an inguinolabial swelling with variable clinical profile. hydrocoele of canal of nuck takes origin from failure of transitory reproductive anlagen to regress and is thus analogous to patent processus vaginalis. its true incidence is speculative, with just several hundred cases globally. we aim to provide insights into surgical patient management for a rare entity during the covid-19 outbreak, from the unique perspective of a small rural hospital in scotland. we report the case of a 32-year-old woman who presented with reducible indirect inguinal hernia and a challenging constellation of symptoms, signs and radiographic findings. surgical approach superseded conservative management when the patient's abdomen became acute, with a rising lactate and haemodynamic instability. specifically, the presence of a fluid collection was concerning for sinister acute pathology. our patient was rediagnosed intraoperatively with hydrocoele of canal of nuck. this so-called 'female hydrocoele' is an eponymous anatomical rarity in general surgery, presenting as an inguinolabial swelling with variable clinical profile. hydrocoele of canal of nuck takes origin from failure of transitory reproductive anlagen to regress and is thus analogous to patent processus vaginalis. its true incidence is speculative, with just several hundred cases globally. we aim to provide insights into surgical patient management for a rare entity during the covid-19 outbreak, from the unique perspective of a small rural hospital in scotland. hydrocoele of nuck usually presents clinically as a painless to moderately tender, irreducible lump in the inguinolabial region. the presentation varies according to morphology, as well as unpropitious sequelae, and there is no single set of signs lending to a consistent clinical profile. 1 when encysted, or associated with infection or endometriosis, the swelling is severely painful and incarcerated inguinal hernia will be the primary differential diagnosis. 2 communicating hydrocoele and indirect inguinal hernia are caused by incomplete regression of the processus vaginalis, allowing either a patent channel to communicate with the peritoneum or formation of a potential space that is morphologically encysted. [3] [4] [5] thus, the extent to which the hydrocoele traverses the canal depends on how much of the canal remains patent. theoretically, the hydrocoele may be contiguous from deep inguinal ring to labium majus, or manifest as a cyst with rostral and caudal boundaries anywhere along this tract. the cysts seldom exceed 3 cm in length or a diameter of 0.5 cm. 6 7 the incidence in female adults is estimated to be in the region of 400 globally. 5 7 that said, true incidence remains elusive and grossly underestimated as a result of misdiagnosis and under-reporting. [8] [9] [10] [11] this 32-year-old female sports instructor presented via her general practitioner for left iliac fossa bulge associated with lower abdominal pain without radiation. she was triaged for covid-19 by our emergency department, having nil symptoms but stratifying as covid-19 vulnerable because of complex asthma. the abdominal pain elapsed 4 days, but was progressively worsening in frequency and sharpness and associated with nausea but not vomitus. the bulge did not increase in size during this time; bowels were opening ordinarily and there were nil urinary symptoms. there was a history of intractable asthma and recurrent ovarian cysts which had previously required gynaecological surgical intervention. nine years prior, right oophorectomy was performed as part of an exploratory laparotomy and proceed for torsion of large dermoid cyst of ovary. four years ago, she underwent laparoscopic adhesiolysis for ongoing dysparaeunia and infertility. cystectomy was also carried out on the remaining ovary in the interim under private healthcare. the final gynaecological encounter to date was in 2019, in which haemorrhagic left ovarian cyst was managed conservatively and spontaneously resorbed. on examination, the inguinal bulge was superomedial to the pubic tubercle and behaved like a reducible indirect inguinal hernia. the hernia remained in place following manual reduction and there was no peristaltic activity, nor any associated vascularity. observations and blood tests were entirely unremarkable. simple analgesia brought effective pain relief and the patient was given a worsening statement before discharge. this conservative approach was justified by virtue of elective surgery precautions during the covid-19 pandemic. national guidelines have mandated minimising high-risk aerosol generating procedures including general anaesthesia and surgery. as such, elective surgery is deferred and only emergency surgery is being performed. at this stage, the patient was stratified for home management by a uk government covid-19 discharge to assess model. 12 the patient returned by ambulance 24 hours later, this time hypotensive and feverish and now exquisitely painful in the lower abdomen. as she still had no symptoms suspicious for covid-19, she was cohorted according to local adaptations of national policy in our rural hospital's 'green' (covid-19 free) zone. given the background of intractable asthma, cohorting also had the unusual association of diseases/symptoms embedded benefit of conferring her protection as a covid-19vulnerable patient. there was now distension in the inguinal region, which precluded appreciation of any discrete lump. pain was also more severe than the day prior, being controlled initially with entonox and then requiring 5 mg intravenous morphine. respiratory alkalosis and a rising lactate were notable findings on arterial blood gas. she was still apyrexial with nil symptoms of covid-19 and she was not peritonitic. the ensuing workup was templated against differential diagnoses including incarcerated hernia and adnexal abnormality in view of her medical history. on day 1, ultrasound scan of the left inguinal region was convincing for inguinal hernia and negative for femoral hernia. (figure 1) appearance was of a thin-walled cystic mass which did not change with valsalva manoeuvre. presence of bowel in the swelling was excluded, while the fluid component was tentatively interpreted as inflammation amidst scan limitations and clinical unfamiliarity. when the patient represented to us 24 hours later, a negative beta-human chorionic gonadotropin (hcg) was ensured before investigation with abdominal x-ray. there were clear signs of heavy faecal loading without small bowel obstruction. ct abdomen and pelvis ruled out adnexal anomaly but further demonstrated the unexpected finding of free fluid in the left inguinal canal. while there was nil herniation of bowel contents, the fluid collection in the sac was now concerning for possible bowel perforation and an evolving peritonitis (figures 2 and 3). 100 ml oral gastrograffin was then administered to achieve duality of therapeutic effect and diagnosis, namely bowel clearance and to interrogate the bowel for any pathology or other cause of the fluid collection. no ostensible pathology was evident. due to clinical deterioration, informed consent was obtained for inguinal region exploration and mesh repair of the reducible left inguinal hernia. full personal protective equipment was donned and minimal personnel were present in theatre in accordance with joint national and health protection society guidelines. 12 13 spinal and regional anaesthesia was opted for instead of general anaesthesia to mitigate against unnecessary aerosol generating procedures and in view of the patient having complex asthma. surgical exploration of the left inguinal region revealed the presence of a small hernial sac. surprisingly, a cystic lesion with dark fluid and size 2×2 cm was discovered, explaining the radiological findings. thus, an intraoperative diagnosis of hydrocoele of canal of nuck was made. surgical excision of the cystic hydrocoele was performed. the hydrocoele was easily ligated from proximal tissue planes and after total separation, high release of the canal of nuck was performed, thereby facilitating excision of the cyst. following herniotomy and excision of the sac, herniorrhaphy with tightening of the deep inguinal ring and hernioplasty was performed using large pore monofilament propylene mesh 10×5 cm for reinforcement of the posterior wall. good haemostasis was achieved for the rest of the procedure. postoperatively, we observed an uneventful recovery. the patient was discharged home the following morning with basic pain relief and instructions for wound care. our patient presented 10 days postoperatively with subcutaneous haematoma at the surgical wound site. this was drained in clinic and the wound was redressed. prophylactic antibiotics were dispensed for 1 week. she recovered completely with no further attendances. hydrocoele and indirect inguinal hernia share a kindred aetiology in both sexes. this is demonstrated by tracing anatomy back to common fetal ontogeny, in which the processus vaginalis extends as a tubular outpouching of the peritoneal cavity and abdominal wall layers. the gonadal guide-an anlage called gaubernaculum-aids descent of the developing gonads to their final destinations in the pelvis or scrotum. the course is relatively shorter in women than men, with gaubernaculum regressing distally to leave the round ligament of uterus as a fetal remnant. 14 15 in men, the spermatic cord dominates the inguinal canal and this relatively greater spatial occupancy is responsible for an inguinal region that is more prone to hydrocoele and hernia. when there is incomplete obliteration of processus vaginalis, a communicating or non-communicating potential space is formed. in the former, an indirect inguinal hernia may develop. 1 in both, hydrocoele may develop, with mixed, communicating or cystic morphology (figure 4). 3 6 7 the clinical profile of hydrocoele of canal of nuck benali et al 11 have provided a narrative synthesis of hydrocoele of canal of nuck using the literature base. there is no ostensible pattern regarding reducibility of the hernia, or whether or not it is painful. 1 5 15 16 the most frequent sign of nuck hydrocoele is inguinolabial lump or swelling, rendering it clinically indistinguishable from inguinal hernia. 11 14 indeed, matsumoto et al 9 coined the term 'inguinal hernia mimic' for hydrocoele of nuck because of its changeable mass. 9 ultrasonography is the gold standard imaging for hydrocoele of canal of nuck, with benefit derived from the live nature of the imaging. the presence of bowel can also be adequately confirmed or excluded in the hernial sac. cardinal ultrasonographic signs include a homogenous, cystic, superficial mass which does not change with valsalva manoeuvre. 15 17 18 the intraoperative experience is also subject to variation. one demonstration is that cystic hydrocoele fluid content seems to differ, with bhattacharjee and ghosh 19 and topal et al 7 having described a light or serous fluid, while mandhan et al 2 and matsumoto et al 9 had encountered dark fluid on rupture of the cyst, similar to our own case. 2 7 9 19 we found clinical and radiographic findings intriguing and unfamiliar, producing a diagnostic dilemma which was only resolved intraoperatively. 20 we report successful implementation of covid-19 guidelines in a rural surgical setting. our scenario was complex, by virtue of our rurality, the covid-19 pandemic and lastly the patient's rapid decline with an indeterminate surgical diagnosis. while our patient had nil covid-19 symptoms, we favoured peripheral and neuraxial nerve blocks in order to minimise the overall burden of aerosol generating procedures. by opting for regional and spinal anaesthesia as opposed to general anaesthesia, our anaesthesia protocol spared bag and mask ventilation, endotracheal intubation and suctioning, all of which involve aerosolization and confer greater risk of respiratory secretion exposure and viral transmission. 21 22 a commissioner report by the uk government in march 2020 acknowledged covid-19 as an 'unprecedented challenge' for health and social care services. 23 we implemented pre-emptive measures to safeguard the well-being of acute patients, including the safe, streamlined discharge of non-emergency patients and strict conservation of high-risk procedures including surgery. 12 according to the who's covid-19 readiness checklist, such an approach is strategic for relieving pressure and creating additional hospital capacity for surge demand. 22 this is even more germane in a remote and rural hospital in the north of scotland which has already experienced clusters of patients who are covid-19 positive. in accessory to the above, the 'hospital discharge service requirements' guidance was charted in tandem with strategic coordination groups across the national health service. when our 32-year-old woman was clinically stable, our surgeon in charge entered her into 'pathway 1' of the covid-19 'discharge to assess model', which is a viable portal for an estimated 45% of patient influx in the uk. here, the patient is fit for discharge with a short-term supported recovery at home. a responsible point of contact is agreed on, and the patient has a worsening statement to help facilitate further contact if needed. 12 22 when our patient presented back to us with worsening condition, we promptly admitted and made the decision to operate after obtaining informed consent. the interface between conservative and emergency management is evident on day 1 versus day 2 and was justified by the guidelines. crucially, covid-19 guideline adherence was abided without simultaneously jeopardising patient safety. unusual association of diseases/symptoms conclusion by raising awareness of this condition, general surgeons may append hydrocoele of canal of nuck to their roster of differential diagnoses and spare their patients from overinvestigation. ultrasound remains the gold standard for imaging female hydrocoeles. the clinical profile is mutable and challenging to interpret; therefore, surgery is usually opted with the intention to repair a hernia. surgery simultaneously forms the definitive management of hydrocoele of canal of nuck as well as providing an intraoperative, revised diagnosis. we have provided insight into surgery during pandemics from the unique perspective of a small yet busy scottish rural hospital. with this exceptionally rare case, we demonstrate the feasibility of implementing covid-19 strategies for surgical management of a patient belonging to a highrisk covid-19 vulnerable subgroup. ► inconsistent clinical profile and clinical unfamiliarity often preclude the preoperative diagnosis of hydrocoele of canal of nuck. ► radiology and ultrasonography findings distinguish hydrocoele of canal of nuck from inguinal hernias. ► surgery in pandemics: successful management of a rare surgical patient is possible with appropriate risk stratification and implementation of covid-19 strategies. hydrocele of the canal of nuck (female hydrocele): a rare differential for inguino-labial swelling infected hydrocele of the canal of nuck hydrocele of the canal of nuck laparoscopic intracorporeal hydrocelectomy and posterior wall suture repair of the hydrocele for the canal of nuck hydrocele of the canal of nuck presenting as a sausage-shaped mass nonobliteration of the processus vaginalis cyst of the canal of nuck mimicking inguinal hernia the presentation of asymptomatic palpable movable mass in female inguinal hernia laparoscopic diagnosis and treatment of a hydrocele of the canal of nuck extending in the retroperitoneal space: a case report hydrocele of canal of nuck cyst of nuck: the importance of histopathological evaluation reducing the risk of transmission of covid-19 in the hospital setting covid-19 personal protective equipment (ppe) hydrocele of the canal of nuck: a case report with magnetic resonance hydrography findings a cautionary approach to adult female groin swelling: hydrocoele of the canal of nuck with a review of the literature female hydrocele of the canal of nuck: a case report imaging of groin masses: inguinal anatomy and pathologic conditions revisited laparoscopic excision of cyst of canal of nuck hydrocele of the canal of nuck hydrocele of the canal of nuck: ultrasound appearance practical considerations for performing regional anesthesia: lessons learned from the covid-19 pandemic world health organisation hospital readiness checklist for covid-19 covid-19 hospital discharge service requirements acknowledgements special thanks to radiographer niall lloyd for provision of images and reconstructions. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. provenance and peer review not commissioned; externally peer reviewed.this article is made freely available for use in accordance with bmj's website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by bmj. you may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained. ahmed hazem helmy http:// orcid. org/ 0000-0002-3478-2990 key: cord-341919-8gnthufw authors: basi, saajan; hamdan, mohammad; punekar, shuja title: clinical course of a 66-year-old man with an acute ischaemic stroke in the setting of a covid-19 infection date: 2020-08-23 journal: bmj case rep doi: 10.1136/bcr-2020-235920 sha: doc_id: 341919 cord_uid: 8gnthufw a 66-year-old man was admitted to hospital with a right frontal cerebral infarct producing left-sided weakness and a deterioration in his speech pattern. the cerebral infarct was confirmed with ct imaging. the only evidence of respiratory symptoms on admission was a 2 l oxygen requirement, maintaining oxygen saturations between 88% and 92%. in a matter of hours this patient developed a greater oxygen requirement, alongside reduced levels of consciousness. a positive covid-19 throat swab, in addition to bilateral pneumonia on chest x-ray and lymphopaenia in his blood tests, confirmed a diagnosis of covid-19 pneumonia. a proactive decision was made involving the patients’ family, ward and intensive care healthcare staff, to not escalate care above a ward-based ceiling of care. the patient died 5 days following admission under the palliative care provided by the medical team. a 66-year-old man was admitted to hospital with a right frontal cerebral infarct producing left-sided weakness and a deterioration in his speech pattern. the cerebral infarct was confirmed with ct imaging. the only evidence of respiratory symptoms on admission was a 2 l oxygen requirement, maintaining oxygen saturations between 88% and 92%. in a matter of hours this patient developed a greater oxygen requirement, alongside reduced levels of consciousness. a positive covid-19 throat swab, in addition to bilateral pneumonia on chest x-ray and lymphopaenia in his blood tests, confirmed a diagnosis of covid-19 pneumonia. a proactive decision was made involving the patients' family, ward and intensive care healthcare staff, to not escalate care above a ward-based ceiling of care. the patient died 5 days following admission under the palliative care provided by the medical team. coronavirus 2) is a new strain of coronavirus that is thought to have originated in december 2019 in wuhan, china. in a matter of months, it has erupted from non-existence to perhaps the greatest challenge to healthcare in modern times, grinding most societies globally to a sudden halt. consequently, the study and research into sars-cov-2 is invaluable. although coronaviruses are common, sars-cov-2 appears to be considerably more contagious. the who figures into the 2003 sars-cov-1 outbreak, from november 2002 to july 2003, indicate a total of 8439 confirmed cases globally. 1 in comparison, during a period of 4 months from december 2019 to july 2020, the number of global cases of covid-19 reached 10 357 662, increasing exponentially, illustrating how much more contagious sars-cov-2 has been. 2 previous literature has indicated infections, and influenza-like illness have been associated with an overall increase in the odds of stroke development. 3 there appears to be a growing correlation between covid-19 positive patients presenting to hospital with ischaemic stroke; however, studies investigating this are in progress, with new data emerging daily. this patient report comments on and further characterises the link between covid-19 pneumonia and the development of ischaemic stroke. at the time of this patients' admission, there were 95 positive cases from 604 covid-19 tests conducted in the local community, with a predicted population of 108 000. 4 only 4 days later, when this patient died, the figure increased to 172 positive cases (81% increase), illustrating the rapid escalation towards the peak of the pandemic, and widespread transmission within the local community (figure 1). as more cases of ischaemic stroke in covid-19 pneumonia patients arise, the recognition and understanding of its presentation and aetiology can be deciphered. considering the virulence of sars-cov-2 it is crucial as a global healthcare community, we develop this understanding, in order to intervene and reduce significant morbidity and mortality in stroke patients. a 66-year-old man presented to the hospital with signs of left-sided weakness. the patient had a background of chronic obstructive pulmonary disease (copd), atrial fibrillation and had one previous ischaemic stroke, producing left-sided haemiparesis, which had completely resolved. he was a non-smoker and lived in a house. the patient was found slumped over on the sofa at home on 1 april 2020, by a relative at approximately 01:00, having been seen to have no acute medical illness at 22:00. the patients' relative initially described disorientation and agitation with weakness noted in the left upper limb and dysarthria. at the time of presentation, neither the patient nor his relative identified any history of fever, cough, shortness of breath, loss of taste, smell or any other symptoms; however, the patient did have a prior admission 9 days earlier with shortness of breath. the vague nature of symptoms, entwined with considerable concern over approaching the hospital, due to the risk of contracting covid-19, created a delay in the patients' attendance to the accident and emergency department. his primary survey conducted at 09:20 on 1 april 2020 demonstrated a patent airway, with spontaneous breathing and good perfusion. his glasgow coma scale (gcs) score was 15 (a score of 15 is the highest level of consciousness), his blood glucose was 7.2, and he did not exhibit any signs of trauma. his abbreviated mental test score was 7 out of 10, indicating a degree of altered cognition. an ecg demonstrated atrial fibrillation with a normal heart rate. his admission weight measured 107 kg. at 09:57 new disease the patient required 2 l of nasal cannula oxygen to maintain his oxygen saturations between 88% and 92%. he started to develop agitation associated with an increased respiratory rate at 36 breaths per minute. on auscultation of his chest, he demonstrated widespread coarse crepitation and bilateral wheeze. throughout he was haemodynamically stable, with a systolic blood pressure between 143 mm hg and 144 mm hg and heart rate between 86 beats/min and 95 beats/min. from a neurological standpoint, he had a mild left facial droop, 2/5 power in both lower limbs, 2/5 power in his left upper limb and 5/5 power in his right upper limb. tone in his left upper limb had increased. this patient was suspected of having covid-19 pneumonia alongside an ischaemic stroke. a ct of his brain conducted at 11:38 on 1 april 2020 (figure 2) illustrated an ill-defined hypodensity in the right frontal lobe medially, with sulcal effacement and loss of grey-white matter. this was highly likely to represent acute anterior cerebral artery territory infarction. furthermore an oval low-density area in the right cerebellar hemisphere, that was also suspicious of an acute infarction. these vascular territories did not entirely correlate with his clinical picture, as limb weakness is not as prominent in anterior cerebral artery territory ischaemia. therefore this left-sided weakness may have been an amalgamation of residual weakness from his previous stroke, in addition to his acute cerebral infarction. an erect ap chest x-ray with portable equipment (figure 3) conducted on the same day demonstrated patchy peripheral consolidation bilaterally, with no evidence of significant pleural effusion. the pattern of lung involvement raised suspicion of covid-19 infection, which at this stage was thought to have provoked the acute cerebral infarct. clinically significant blood results from 1 april 2020 demonstrated a raised c-reactive protein (crp) at 215 mg/l (normal 0-5 mg/l) and lymphopaenia at 0.5×10 9 (normal 1×10 9 to 3×10 9 ). other routine blood results are provided in table 1. interestingly the patient, in this case, was clinically assessed in the accident and emergency department on 23 march 2020, 9 days prior to admission, with symptoms of shortness of breath. his blood results from this day showed a crp of 22 mg/l and a greater lymphopaenia at 0.3×10 9 . he had a chest x-ray (figure 4), which indicated mild radiopacification in the left mid zone. he was initially treated with intravenous co-amoxiclav and ciprofloxacin. the following day he had minimal symptoms (curb 65 score 1 for being over 65 years). given improving blood results (declining crp), he was discharged home with a course of oral amoxicillin and clarithromycin. as national governmental restrictions due to covid-19 had not been formally announced until 23 march 2020, and inconsistencies regarding personal protective equipment training and usage existed during the earlier stages of this rapidly evolving pandemic, it is possible that this patient contracted covid-19 within the local community, or during his prior hospital admission. it could be argued that the patient had early covid-19 signs and symptoms, having presented with shortness of breath, lymphopaenia, and having had subtle infective chest x-ray changes. the patient explained he developed a stagnant productive cough, which began 5 days prior to his attendance to hospital on 23 march 2020. he responded to antibiotics, making a full recovery following 7 days of treatment. this information does not assimilate with the typical features of a covid-19 infection. a diagnosis of community-acquired pneumonia or infective exacerbation of copd seem more likely. however, given the high incidence of covid-19 infections during this patients' illness, an exposure and early covid-19 illness, prior to the 23 march 2020, cannot be completely ruled out. on the current admission, this patient was managed with nasal cannula oxygen at 2 l. by the end of the day, this had progressed to a venturi mask, requiring 8 l of oxygen to maintain oxygen saturation. he had also become increasingly drowsy and confused, his gcs declined from 15 to 12. however, the patient was still haemodynamically stable, as he had been in the morning. an arterial blood gas demonstrated a respiratory alkalosis (ph 7.55, pco 2 3.1, po 2 6.7 and hco 3 24.9, lactate 1.8, base excess 0.5). he was commenced on intravenous co-amoxiclav and ciprofloxacin, to treat a potential exacerbation of copd. this patient had a covid-19 throat swab on 1 april 2020. before the result of this swab, an early discussion was held with the intensive care unit staff, who decided at 17:00 on 1 april 2020 that given the patients presentation, rapid deterioration, comorbidities and likely covid-19 diagnosis he would not be for escalation to the intensive care unit, and if he were to deteriorate further the end of life pathway would be most appropriate. the discussion was reiterated to the patients' family, who were in agreement with this. although he had evidence of an ischaemic stroke on ct of his brain, it was agreed by all clinicians that intervention for this was not as much of a priority as providing optimal palliative care, therefore, a minimally invasive method of treatment was advocated by the stroke team. the patient was given 300 mg of aspirin and was not a candidate for fibrinolysis. the following day, before the throat swab result, had appeared the patient deteriorated further, requiring 15 l of oxygen through a non-rebreather face mask at 60% fio 2 to maintain his oxygen saturation, at a maximum of 88% overnight. at this point, he was unresponsive to voice, with a gcs of 5. although, he was still haemodynamically stable, with a blood pressure of 126/74 mm hg and a heart rate of 98 beats/min. his respiratory rate was 30 breaths/min. his worsening respiratory condition, combined with his declining level of consciousness made it impossible to clinically assess progression of the neurological deficit generated by his cerebral infarction. moreover, the patient was declining sharply while receiving the maximal ward-based treatment available. the senior respiratory physician overseeing the patients' care decided that a palliative approach was in this his best interest, which was agreed on by all parties. the respiratory team completed the 'recognising dying' documentation, which signified that priorities of care had shifted from curative treatment to palliative care. although the palliative team was not formally involved in the care of the patient, the patient received comfort measures without further attempts at supporting oxygenation, or conduction of regular clinical observations. the covid-19 throat swab confirmed a positive result on 2 april 2020. the patient was treated by the medical team under jurisdiction of the hospital palliative care team. this included the prescribing of anticipatory medications and a syringe driver, which was established on 3 april 2020. his antibiotic treatment, non-essential medication and intravenous fluid treatment were discontinued. his comatose condition persisted throughout the admission. once the patients' gcs was 5, it did not improve. the patient was pronounced dead by doctors at 08:40 on 5 april 2020. sars-cov-2 is a type of coronavirus that was first reported to have caused pneumonia-like infection in humans on 3 december 2019. 5 as a group, coronaviruses are a common cause of upper and lower respiratory tract infections (especially in children) and have been researched extensively since they were first characterised in the 1960s. 6 to date, there are seven coronaviruses that are known to cause infection in humans, including sars-cov-1, the first known zoonotic coronavirus outbreak in november 2002. 7 coronavirus infections pass through communities during the winter months, causing small outbreaks in local communities, that do not cause significant mortality or morbidity. sars-cov-2 strain of coronavirus is classed as a zoonotic coronavirus, meaning the virus pathogen is transmitted from nonhumans to cause disease in humans. however the rapid spread of sars-cov-2 indicates human to human transmission is present. from previous research on the transmission of coronaviruses and that of sars-cov-2 it can be inferred that sars-cov-2 spreads via respiratory droplets, either from direct inhalation, or indirectly touching surfaces with the virus and exposing the eyes, nose or mouth. 8 common signs and symptoms of the covid-19 infection identified in patients include high fevers, severe fatigue, dry cough, acute breathing difficulties, bilateral pneumonia on radiological imaging and lymphopaenia. 9 most of these features were identified in this case study. the significance of covid-19 is illustrated by the speed of its global spread and the potential to cause severe clinical presentations, which as of april 2020 can only be treated symptomatically. in italy, as of mid-march 2020, figure 4 chest x-ray conducted on prior admission illustrating mild radiopacification in the left mid zone. it was reported that 12% of the entire covid-19 positive population and 16% of all hospitalised patients had an admission to the intensive care unit. 10 the patient, in this case, illustrates the clinical relevance of understanding covid-19, as he presented with an ischaemic stroke underlined by minimal respiratory symptoms, which progressed expeditiously, resulting in acute respiratory distress syndrome and subsequent death. our case is an example of a new and ever-evolving clinical correlation, between patients who present with a radiological confirmed ischaemic stroke and severe covid-19 pneumonia. as of april 2020, no comprehensive data of the relationship between ischaemic stroke and covid-19 has been published, however early retrospective case series from three hospitals in wuhan, china have indicated that up to 36% of covid-19 patients had neurological manifestations, including stroke. 11 these studies have not yet undergone peer review, but they tell us a great deal about the relationship between covid-19 and ischaemic stroke, and have been used to influence the american heart associations 'temporary emergency guidance to us stroke centres during the covid-19 pandemic'. 12 the relationship between similar coronaviruses and other viruses, such as influenza in the development of ischaemic stroke has previously been researched and provide a basis for further investigation, into the prominence of covid-19 and its relation to ischaemic stroke. 3 studies of sars-cov-2 indicate its receptor-binding region for entry into the host cell is the same as ace2, which is present on endothelial cells throughout the body. it may be the case that sars-cov-2 alters the conventional ability of ace2 to protect endothelial function in blood vessels, promoting atherosclerotic plaque displacement by producing an inflammatory response, thus increasing the risk of ischaemic stroke development. 13 other hypothesised reasons for stroke development in covid-19 patients are the development of hypercoagulability, as a result of critical illness or new onset of arrhythmias, caused by severe infection. some case studies in wuhan described immense inflammatory responses to covid-19, including elevated acute phase reactants, such as crp and d-dimer. raised d-dimers are a non-specific marker of a prothrombotic state and have been associated with greater morbidity and mortality relating to stroke and other neurological features. 14 arrhythmias such as atrial fibrillation had been identified in 17% of 138 covid-19 patients, in a study conducted in wuhan, china. 15 in this report, the patient was known to have atrial fibrillation and was treated with rivaroxaban. the acute inflammatory state covid-19 is known to produce had the potential to create a prothrombotic environment, culminating in an ischaemic stroke. some early case studies produced in wuhan describe patients in the sixth decade of life that had not been previously noted to have antiphospholipid antibodies, contain the antibodies in blood results. they are antibodies signify antiphospholipid syndrome; a prothrombotic condition. 16 this raises the hypothesis concerning the ability of covid-19 to evoke the creation of these antibodies and potentiate thrombotic events, such as ischaemic stroke. no peer-reviewed studies on the effects of covid-19 and mechanism of stroke are published as of april 2020; therefore, it is difficult to evidence a specific reason as to why covid-19 patients are developing neurological signs. it is suspected that a mixture of the factors mentioned above influence the development of ischaemic stroke. if we delve further into this patients' comorbid state exclusive to covid-19 infection, it can be argued that this patient was already at a relatively higher risk of stroke development compared with the general population. the fact this patient had previously had an ischaemic stroke illustrates a prior susceptibility. this patient had a known background of hypertension and atrial fibrillation, which as mentioned previously, can influence blood clot or plaque propagation in the development of an acute ischaemic event. 15 although the patient was prescribed rivaroxaban as an anticoagulant, true consistent compliance to rivaroxaban or other medications such as amlodipine, clopidogrel, candesartan and atorvastatin cannot be confirmed; all of which can contribute to the reduction of influential factors in the development of ischaemic stroke. furthermore, the fear of contracting covid-19, in addition to his vague symptoms, unlike his prior ischaemic stroke, which demonstrated dense left-sided haemiparesis, led to a delay in presentation to hospital. this made treatment options like fibrinolysis unachievable, although it can be argued that if he was already infected with covid-19, he would have still developed life-threatening covid-19 pneumonia, regardless of whether he underwent fibrinolysis. it is therefore important to consider that if this patient did not contract covid-19 pneumonia, he still had many risk factors that made him prone to ischaemic stroke formation. thus, we must consider whether similar patients would suffer from ischaemic stroke, regardless of covid-19 infection and whether covid-19 impacts on the severity of the stroke as an entity. having said this, the management of these patients is dependent on the likelihood of a positive outcome from the covid-19 infection. establishing the ceiling of care is crucial, as it prevents incredibly unwell or unfit patients' from going through futile treatments, ensuring respect and dignity in death, if this is the likely outcome. it also allows for the provision of limited or intensive resources, such as intensive care beds or endotracheal intubation during the covid-19 pandemic, to those who are assessed by the multidisciplinary team to benefit the most from their use. the way to establish this ceiling of care is through an early multidisciplinary discussion. in this case, the patient did not convey his wishes regarding his care to the medical team or his family; therefore it was decided among intensive care specialists, respiratory physicians, stroke physicians and the patients' relatives. the patient was discussed with the intensive care team, who decided that as the patient sustained two acute life-threatening illnesses simultaneously and had rapidly deteriorated, ward-based care with a view to palliate if the further deterioration was in the patients' best interests. these decisions were not easy to make, especially as it was on the first day of presentation. this decision was made in the context of the patients' comorbidities, including copd, the patients' age, and the availability of intensive care beds during the steep rise in intensive care admissions, in the midst of the covid-19 pandemic (figure 1). furthermore, the patients' rapid and permanent decline in gcs, entwined with the severe stroke on ct imaging of the brain made it more unlikely that significant and permanent recovery could be achieved from mechanical intubation, especially as the damage caused by the stroke could not be significantly reversed. as hospitals manage patients with covid-19 in many parts of the world, there may be tension between the need to provide higher levels of care for an individual patient and the need to preserve finite resources to maximise the benefits for most patients. this patient presented during a steep rise in intensive care admissions, which may have influenced the early decision not to treat the patient in an intensive care setting. retrospective studies from wuhan investigating mortality in patients with multiple organ failure, in the setting of covid-19, requiring intubation have demonstrated mortality can be up to 61.5%. 17 the mortality risk is even higher in those over 65 years of age with respiratory comorbidities, indicating why this patient was unlikely to survive an admission to the intensive care unit. 18 regularly updating the patients' family ensured cooperation, empathy and sympathy. the patients' stroke was not seen as a priority given the severity of his covid-19 pneumonia, therefore the least invasive, but most appropriate treatment was provided for his stroke. the british association of stroke physicians advocate this approach and also request the notification to their organisation of covid-19-related stroke cases, in the uk. 19 learning points ► sars-cov-2 (severe acute respiratory syndrome coronavirus 2) is one of seven known coronaviruses that commonly cause upper and lower respiratory tract infections. it is the cause of the 2019-2020 global coronavirus pandemic. ► the significance of covid-19 is illustrated by the rapid speed of its spread globally and the potential to cause severe clinical presentations, such as ischaemic stroke. ► early retrospective data has indicated that up to 36% of covid-19 patients had neurological manifestations, including stroke. ► potential mechanisms behind stroke in covid-19 patients include a plethora of hypercoagulability secondary to critical illness and systemic inflammation, the development of arrhythmia, alteration to the vascular endothelium resulting in atherosclerotic plaque displacement and dehydration. ► it is vital that effective, open communication between the multidisciplinary team, patient and patients relatives is conducted early in order to firmly establish the most appropriate ceiling of care for the patient. contributors sb was involved in the collecting of information for the case, the initial written draft of the case and researching existing data on acute stroke and covid-19. he also edited drafts of the report. mh was involved in reviewing and editing drafts of the report and contributing new data. sp oversaw the conduction of the project and contributed addition research papers. funding the authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. competing interests none declared. patient consent for publication next of kin consent obtained. provenance and peer review not commissioned; externally peer reviewed. this is an open access article distributed in accordance with the creative commons attribution non commercial (cc by-nc 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. see: http:// creativecommons. org/ licenses/ by-nc/ 4. 0/. saajan basi http:// orcid. org/ 0000-0002-7441-6952 who | cumulative number of reported probable cases 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