Archives of Academic Emergency Medicine. 2022; 10(1): e66 OR I G I N A L RE S E A RC H Distinguishing Characteristics of COVID-19-Associated Mucormycosis; a Case Series Seyedhadi Samimiardestani1, Shirin Irani1∗, Mehrdad Hasibi2, Maral Seyedahadi3, Shahin Bastaninejad1, Mohammadreza Firouzifar1, Mojataba Mohammadi Ardehali1, Sina Berijani1, Reza Erfanian1, Mohammad Ali Kazemi4, Afshar Etemadi-Aleagha5, Abolfazl Rahimi6, Kourosh Karimi Yarandi7, Samira Ahadi1 1. Otorhinolaryngology Research Center, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran. 2. Infectious Disease Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran. 3. Neurology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran. 4. Department of Radiology, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran. 5. Department of Anesthesiology, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran. 6. Department of Ophthalmology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. 7. Department of Neurosurgery, Tehran University of Medical Sciences, Tehran, Iran. Received: June 2022; Accepted: July 2022; Published online: 18 August 2022 Abstract: Introduction: Since the emergence of COVID-19 pandemic, several articles have reported the co-existence of mucormycosis and COVID-19. This study aimed to distinguish the characteristics of COVID-19-associated rhinocerebral mucormycosis. Methods: In this case series, 18 patients with COVID-19-associated rhinocerebral mucormycosis and unique clinical manifestations and outcomes, who were referred to Amiralam Hospital, a tertiary otorhinolaryngology center, Tehran, Iran, during the COVID-19 era, were reported. Results: Eighteen patients with the mean age of 62.0 ± 11.6 (range: 42 – 83) years were studied (50% males). The mean time in- terval between diagnosis of COVID-19 and first manifestation of mucormycosis was 15.5 ± 9.7 days. The most common presenting symptom was facial paresthesia (72.2%). Fifty percent of patients developed frozen eye. Palatal necrosis was seen in 7 cases (38.8%). Remarkably, facial paralysis was observed in 5 (27.7%) patients. Another notable clinical picture was cavernous sinus thrombosis, seen in 7 patients. We also had two cases of carotid artery occlusion. Three patients, unfortunately, passed away. Conclusion: Rhinocerebral mucormycosis is one of the most important complications of COVID-19 patients, especially those with underlying diseases. It seems that the key to proper management of mucormycosis is early diagnosis and timely intervention, which could give a patient a chance to live more. Keywords: COVID-19; Mycoses; mucormycosis; paranasal sinuses Cite this article as: Samimiardestani S, Irani S, Hasibi M, Seyedahadi M, Bastaninejad S, Firouzifar M, Mohammadi Ardehali M, Berijani S, Erfanian R, Kazemi MA, Etemadi-Aleagha A, Rahimi A, Karimi Yarandi K, Ahadi S. Distinguishing Characteristics of COVID-19-Associated Mucormycosis; a Case Series. Arch Acad Emerg Med. 2022; 10(1): e66. https://doi.org/10.22037/aaem.v10i1.1644. 1. Introduction COVID-19 pandemic is a crisis associated with consider- able mortality and morbidity. Several COVID-19-associated complications have been described in the literature. Bacte- rial and fungal co-infections are among major complications ∗Corresponding Author: Shirin Irani; Amiralam Hospital, North Sa’di Street, Enghelab Street, Tehran, Iran. Fax Number: +98 2166343177, Email: sh_irani@razi.tums.ac.ir, ORCID: https://orcid.org/0000-0002-7770-8950 . that may increase the mortality rate of COVID-19 cases [1]. Mucromycosis is a serious but rare fungal infection caused by mucormycetes. Patients with underlying diseases, especially diabetes mellitus and immunodeficiency are highly vulnera- ble to mucormycosis [2]. It rarely affects immunocompetent patients [3]. Rhinocerebral involvement is the classic mani- festation of mucormycosis. The incidence rate of rhinocere- bral mucormycosis is approximately 1.7 per 1,000,000 of nor- mal population, and its mortality rate is estimated at 40% to 80% [4]. Rhinocerebral mucormycosis usually presents in an acute setting. It originates from the nasal cavity and This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem S. Samimiardestani et al. 2 paranasal sinuses, and spreads to the adjacent structures in- cluding the palate, pharynx, orbits, and the brain [5, 6]. In- fection can spread to the meninges or the brain through the nerves, ophthalmic artery, or cribriform plate [7]. Manage- ment includes antifungal therapy, surgical resection, and if possible, reversal of impaired immunity. During the COVID-19 pandemic, we observed a significant rise in rhinocerebral mucormycosis in our ear, nose, and throat (ENT) specialty referral center. In this study, we present clinical manifestations and outcomes of patients with COVID-19-associated mucormycosis (CAM). 2. Methods 2.1. Study design and setting This case series study was performed at Amir Alam Hospi- tal in Tehran, Iran, which is a referral center for ENT condi- tions. During a 9-month period, from August 2020 to June 2021, patients with a diagnosis of rhinocerebral mucormyco- sis, who had concomitant COVID-19 or were diagnosed with and/or treated for COVID-19 within the past three months were included in the study. The protocol of study was ap- proved by Ethics Committee of Tehran University of Medical Sciences (Ethics code: IR.TUMS.AMIRALAM.REC.1401.019) and researchers adhered to the ethical considerations and confidentiality of patients’ information. 2.2. Managements The diagnosis of mucormycosis was made based on the paranasal sinuses’ endoscopic findings and confirmed by positive fungal smear and culture, and histopathological documentation of fungal invasion in the paranasal sinuses and nasal cavity samples. Proper antifungal agent (Liposomal Amphotericin B at 3- 5 mg/kg or conventional Amphotericin B at 1 mg/kg) was started during the first 24 to 48 hours of admission for all the patients. SARS-CoV-2 infection was confirmed using reverse transcription polymerase chain reaction (RT-PCR) and a spi- ral chest computed tomography (CT) scan was performed for all cases to assess lung involvement. Patients with ac- tive COVID-19 were transferred to the COVID-19 ward and received intravenous (IV ) Remdesivir at 200 mg in the first day followed by 100 mg daily for the minimum duration of five days. Soon after stabilization of patients’ general condition as well as the serum glucose and electrolyte levels, endoscopic de- bridement of the paranasal sinuses was performed. The ex- tent of surgical debridement was determined based on the clinical and radiological findings, ranging from simple exci- sion of the necrotic soft tissue and bone in the turbinates and nasal septum to a more extensive procedure including partial or radical maxillectomy and debridement of pterygopalatine fossa, alveolar ridge, and palatal resection even orbital exen- teration or skull base surgery. Intravenous (IV ) Amphotericin B was continued after surgery until a minimum total curative dose of the medication was achieved. The patients under- went weekly endoscopic examination during the admission and re-debridement was performed in the presence of any suspicious necrotic tissue. 2.3. Data gathering We collected the following data for all cases: demographic data, predisposing factors, time interval between COVID- 19 and the onset of mucormycosis, patient’s clinical man- ifestations and intra-operative and endoscopic findings, anatomical extension of the fungal infection, and patient’s outcome (categorized as deceased, still hospitalized, or alive—meaning no more hospitalized). 2.4. Statistical analysis Statistical analysis was done using SPSS version 23 and find- ings were reported as mean ± standard deviation or fre- quency ( 3. Results 3.1. Baseline characteristics of studied cases Eighteen patients with diagnosis of mucormycosis and COVID-19, including 9 males and 9 females, with the mean age of 62.0 ± 11.6 (range: 42 – 83) years were studied. Clinical presentation, treatment, extent of surgery, and outcome of studied patients are summarized in table1 and figure 1. The mean time interval between COVID-19 diagnosis and first manifestation of mucormycosis was 15.6 ± 9.7 days (range from 0 to 43 days). Three patients received antifungal therapy and Remdesivir simultaneously. Twelve out of the 18 patients had received corticosteroids as an adjunct treatment for se- vere COVID-19. Fourteen patients were known cases of dia- betes mellitus (DM), and three patients had new-onset DM. The most common presenting symptom was facial pares- thesia (72.2%). Among our patients, 11 (61%) had ophthal- moplegia, 10 (55.5%) had visual impairment, and 4 patients (22%) had proptosis (Figure 2). Fifty percent of our patients developed frozen eye. Palatal necrosis was seen in 7 cases (38.8%). Remarkably, facial paralysis was observed in 5 pa- tients (27.7%) and it was a presenting symptom in all of them. Interestingly, one of our patients, case No 14, had a 5-month- history of facial paralysis without any other mucormyco- sis manifestations a week after COVID-19 infection. Nasal obstruction was seen in 22% and dark nasal discharge was present in 16% of the patients. The presenting symptom of one patient was fever. One patient had teeth loosening due to hard palate involvement. Two patients presented with loss of consciousness. Another notable clinical picture was cav- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 3 Archives of Academic Emergency Medicine. 2022; 10(1): e66 Table 1: Baseline characteristics, treatment, extent of surgery and outcome of patients with COVID-19-associated mucormycosis No./ sex/ age Predisp- osing factors Steroid Hospi taliza- tion Interv al (days) Signs/symptoms Imaging findings Endoscopy findings Extension of Disease Surgery report Outcome 1/64/F DM, Anemia Y Y 12 Frozen eye, oph- thalmoplegia, vision loss, proptosis, facial paralysis and paresthesia, loss of consciousness Maxillary and ethmoidal sinusitis, PPF involvement, inflammation of orbital muscles, IOF& SOF, orbital apex, fat stranding of intraconal & extraconal fat, oval foramen, CST, carotid vasculitis, buccal abscess and gas bubble in ramus & body of mandible, inferior alveolar nerve involvement, skull base osteomyelitis No evidence of necrosis Buccal, masticator, and parapharyngeal space, orbital apex, PPF, cavernous sinus Antrostomy, ethmoidectomy, sphenoidotomy, buccal abscess drainage/3 times Alive/9- month follow-up 2/58/F DM, HTN, Anemia N Y 14 Facial paralysis and paresthesia, ophthalmople- gia, nasal obstruction, proptosis Sphenoid sinus dehiscence, CST, orbital cellulitis Inferior Turbinate necrosis Masticator and parapharyngeal space Antrostomy, ethmoidectomy, sphenoidotomy, Draf IIb, orbital exenteration/ 3 times Alive/6- month follow-up 3/52/F DM, HTN Y Y 10 Fever, frozen eye, ophthalmo- plegia, visual impairment, proptosis CST Middle turbinate necrosis Medial and superior orbital wall, PPF, cribriform plate, parasellar area and cavernous sinus, orbital apex Ethmoidectomy, antrostomy, PPF debridement, Draf IIb, ITF debridement, orbital decompression/ 2 times Alive/6- month follow-up 4/53/F DM Y Y 21 Cheek paresthesia, ophthalmople- gia Orbital abscess, brain micro-abscess Evidence of previous antrostomy and ethmoidec- tomy, no necrosis Medial and inferior orbital wall, PPF, cribriform plate Ethmoidectomy, antrostomy, orbital decompression and abscess drainage, bilateral PPF debridement/ 2 times Alive/9- month follow-up 5/52/M DM, HTN N Y Simult aneous Frozen eye, vision loss, oph- thalmoplegia, facial paralysis and paresthesia Maxillary and ethmoidal sinusitis, CST Evidence of previous sphenoido- tomy and ethmoidec- tomy, nasal septum necrosis CST, orbit, PPF Ethmoidectomy, antrostomy, bilateral PPF debridement, ITF debridement, orbital decompression/ 3 times Alive/8- month follow-up This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem S. Samimiardestani et al. 4 Table 1: Baseline characteristics, treatment, extent of surgery and outcome of patients with COVID-19-associated mucormycosis No./ sex/ age Predisp- osing factors Steroid Hospi taliza- tion Interv al (days) Signs/symptoms Imaging findings Endoscopy findings Extension of Disease Surgery report Outcome 6/68/M DM, HTN Y N 4 Facial paralysis and paresthesia, nasal obstruction and dark nasal crust, palatal necrosis, blurred vision Maxillary and ethmoidal sinusitis, Nasal septum and Lt. middle turbinate necrosis Lt. hard palate Antrostomy, middle turbinate resection, PPF debridement, partial maxillectomy, ITF debridement Alive/7- month follow- up 7/82/M DM N Y 5 Frozen eye, oph- thalmoplegia, visual loss, dark nasal crust, palatal necrosis, cheek paresthesia Maxillary sinusitis and erosion, PPF, sphenoid sinus, CST Nasal septum and Rt. middle turbinate necrosis PPF, foramen rotundum, ITF No debridement Death 8/47/M DM Y Y 30 Nasal obstruction, Facial swelling Maxillary & ethmoid sinus, PPF, Middle and inferior turbinate necrosis PPF Ethmoidectomy, antrostomy, PPF debridement/ 2 times Alive/1- month follow- up 9/68/M DM, HTN, IHD, Gout Y N 15 days Frozen eye, oph- thalmoplegia, vision loss, facial paresthesia Maxillary & ethmoid sinus & preantral space involvement, orbital apex, intraconal fat haziness Superior, middle, and inferior turbinate necrosis PPF, middle and inferior turbinate Antrostomy, middle turbinate resection, PPF debridement, partial maxillectomy, ITF debridement, retrobulbar amphotericin B injection/3 times Alive/still hospi- talized with good condi- tion 10/67/M DM, HTN Y Y 10 Frozen eye, oph- thalmoplegia, vision loss, facial paresthesia, palatal necrosis Middle and inferior turbinate necrosis PPF, superior, middle, and inferior turbinate Antrostomy, middle turbinate resection, PPF debridement, partial maxillectomy, palatal debridement Death 11/68/M DM, HTN, CKD N Y 43 Facial paresthesia, tooth loosening, palatal necrosis Evidence of previous antrostomy, ethmoidec- tomy and sphenoido- tomy, palatal bone necrosis PPF, middle and inferior turbinate Antrostomy, middle turbinate resection, PPF debridement, partial maxillectomy, palatal debridement Alive/1- month follow- up 12/80/F HTN Y Y 20 Necrosis of nasal septum and palate Mucosal thickening in ethmoid, sphenoid & maxillary sinus, air bubbles in PPF & infratemporal & masticator space (necrotizing fasciitis), orbital apex, intraconal & extraconal space, IOF, SOF Middle and inferior turbinate necrosis, palatal bone necrosis PPF, palatine bone Antrostomy, middle turbinate resection, PPF debridement, partial maxillectomy, palatal debridement Death This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 5 Archives of Academic Emergency Medicine. 2022; 10(1): e66 Table 1: Baseline characteristics, treatment, extent of surgery and outcome of patients with COVID-19-associated mucormycosis No./ sex/ age Predisp- osing factors Steroid Hospi taliza- tion Interv al (days) Signs/symptoms Imaging findings Endoscopy findings Extension of Disease Surgery report Outcome 13/54/M DM Unclear Y 15 Frozen eye, oph- thalmoplegia, vision loss, facial paresthesia, Necrosis in nasal endoscopy PPF Antrostomy, middle turbinate resection, PPF debridement, orbital debridement Alive/2- month follow-up 14/62/F DM N N 7 Facial paresthesia, Facial paralysis PPF, IOF, foramen rotundum, vidian canal, cavernous sinus, buccal and preantral space, ICA C1-C7 thrombosis No evidence of necrosis in diagnostic endoscopy Middle turbinate, PPF, orbit Antrostomy, ethmoidectomy, sphenoidec- tomy, middle turbinate resection, PPF & ITF debridement, debridement of orbital floor, buccal abscess drainage/ 3 times Alive/- month follow-up 15/40/F DM Y Y 15 Frozen eye, oph- thalmoplegia, vision loss, proptosis, facial paresthesia Ethmoid, sphenoid & maxillary sinus, cribriform plate, PPF, IOF, foramen rotundum, vidian canal, buccal and preantral space, orbital apex, cavernous sinus, ICA Evidence of previous antrostomy, ethmoidec- tomy and sphenoido- tomy and new necrosis in posterior septum PPF, ITF fossa, rotundum foramen Antrostomy, ethmoidectomy, sphenoidec- tomy, middle turbinate resection, PPF debridement, debridement of medial and inferior orbital rim, drainage of orbital abscess, orbital exenteration/ 3 times Alive/1- month follow-up 16/57/F DM Y Y 20 Frozen eye, oph- thalmoplegia, vision loss, proptosis, facial paresthesia, dark nasal crust, palatal necrosis Maxillary, ethmoid, sphenoid, PPF, IOF, fat stranding of pre-antral fat, orbital apex, rotundum foramen, vidian canal, fat stranding of buccal, masticator & parapharyngeal space Necrosis in middle turbinate and nasal floor Evidences of previous debridement in another center, PPF, septum and middle turbinate just inferior to cribriform plate Antrostomy, ethmoidectomy, sphenoidec- tomy, middle turbinate resection, PPF debridement, debridement of medial and inferior orbital rim, drainage of orbital abscess, resection of anterior table of frontal sinus & ascending process of maxilla Alive/2- month follow-up This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem S. Samimiardestani et al. 6 Table 1: Baseline characteristics, treatment, extent of surgery and outcome of patients with COVID-19-associated mucormycosis No./ sex/ age Predisp- osing factors Steroid Hospi taliza- tion Interv al (days) Signs/symptoms Imaging findings Endoscopy findings Extension of Disease Surgery report Outcome 17/59/F DM, HTN, IHD Y N 17 Nasal obstruction, facial edema Maxillary, ethmoid, and frontal opacification Necrosis in middle turbinate Maxilla, ethmoid, frontal, PPF Resection of right middle turbinate, antrostomy, sphenoidotomy, anterior & posterior ethmoidectomy, frontal sinusotomy/ 2times Alive/Still hospital- ized with good condition 18/83/M HTN, DM Y Y 20 Palatal necrosis Ethmoid and sphenoid opacification, bone erosion in medial wall of orbit, infraorbital space, greater wing of sphenoid Not performed (directly referred to operation room) Maxillary, ethmoid & sphenoid, palate and alveolar ridge, PPF, inferior orbital fissure Endoscopic maxillectomy, resection of pterygoid processes, ascending process of maxilla, inferior& medial wall of orbit, debridement of pterygoid muscles, palatal & alveolar ridge resection Alive/Still hospital- ized with good condition CST: Cavernous Sinus Thrombosis, DM: Diabetes Mellitus, HTN: Hypertension, ICA: Internal Carotid Artery, IOF: Inferior Orbital Fissure, ITF: Infratemporal Fossa, Lt: left, PPF: Pterygopalatine Fossa, Rt: Right, SOF: Superior Orbital Fissure; IHD: Ischemic Heart Disease; CKD: Chronic Kidney Disease. Figure 1: Percentage of different clinical presentations of patients with COVID-19-associated mucormycosis. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 7 Archives of Academic Emergency Medicine. 2022; 10(1): e66 Figure 2: Magnetic resonance imaging (MRI) without contrast of patient No.1, shows orbital cellulitis, maxillary and ethmoidal sinusitis (A); Left cavernous sinus thrombosis and internal carotid occlusion in patient No 15 (B); Right Cavernous sinus thrombosis and internal carotid occlusion in patient No 14 (C). ernous sinus thrombosis, seen in 7 patients. We had two cases of carotid artery occlusion, without significant neuro- logical manifestations (Figure 2). 3.2. Outcomes Three patients passed away. One of them died before any surgical intervention due to rapid progression of the disease, and the other one died the day after the extensive debride- ment due to necrotizing fasciitis and intracranial involve- ment. The third patient had died due to cardiovascular prob- lems unrelated to mucormycosis disease, a week after the de- bridement. Ultimately, 15 cases were discharged with pre- scription of oral Posaconazole with favorable condition and normal sinus endoscopy. 4. Discussion Since the emergence of the COVID-19 pandemic, several publications have reported the co-existence of mucormyco- sis and COVID-19 disease. It seems that COVID-19 infection may predispose the susceptible patients at risk of developing mucormycosis, especially in patients with DM. Apart from increasing the risk of immunodeficiency, administration of corticosteroids in COVID-19 patients could result in hyper- glycemia, which additionally makes the patients susceptible to mucormycosis. Moreover, alteration of the innate immu- nity due to COVID-19 infection and the microangiopathies causing endothelial damage during COVID-19, are other pre- disposing factors [8, 9]. As a tertiary ENT center, we recog- nized a significant rise in mucormycosis during the COVID- 19 era. Almost all signs and symptoms known to be associated with rhinocerebral mucormycosis were observed in our COVID- 19-associated mucormycosis (CAM) patients. The rapid de- velopment of frozen eye was occasionally seen in mucormy- cosis patients before, but it seems more common in CAM pa- tients. Moreover, facial paralysis is a notable manifestation in our patients. Half of our patients had frozen eye at presen- tation and one-third had facial paralysis, which was consid- erably different from our pre-COVID-19 experience. Bayram et al. reported a case series of CAM patients, in which the most common manifestation was proptosis and 63% of their patients had frozen eye. They did not report facial paralysis as a presenting manifestation of mucormycosis. In that case series, 63% of patients passed away [10]. Patel et al., conducted a multicenter retrospective study in India to investigate the CAM patients. Among 287 mucormy- cosis patients, 187 (65.2%) had CAM. The prevalence of CAM was 0.27% among hospitalized COVID-19 patients. They noted a 2.1-fold rise in mucormycosis during the study pe- riod. The most common underlying disease was uncon- trolled diabetes among CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. The mor- tality rate was 45.7% and was similar in CAM and non-CAM patients [11]. Similarly, in our series, DM was the most com- mon predisposing factor among CAM patients: 13 patients had diabetes and 2 had new-onset diabetes after steroid ad- ministration. Note that 10 patients had a history of steroid administration for treatment of COVID-19. It seems that steroid administration is a double-edged sword for manage- ment of COVID-19 [12]. In a multicenter series from Iran, 15 patients with CAM were reported. Median age of pa- tients was 52 years and 66% were male. The median time interval between diagnosis of mucormycosis and COVID-19 was 7 days, and 86% of patients had diabetes mellitus, while 46.6% received intravenous corticosteroid. Orbital exentera- tion was performed in five patients (33%), while seven (47%) died from mucormycosis [13]. Another unique finding in our cases was cavernous venous sinus thrombosis (CVST). More than half of our patients de- veloped CVST and amazingly all of them survived. To the best of our knowledge, there is no report of CVST among CAM pa- tients in the previous literature. Although, there are reports of CVST among COVID-19 patients [14-16]. Another noteworthy finding in our CAM patients was inter- nal carotid artery (ICA) occlusion. There are several reports This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem S. Samimiardestani et al. 8 about ICA occlusion among COVID-19 patients as well as mucormycosis patients, independently [17-21]. But there were no reports of ICA among CAM patients, to the best of our knowledge. Different studies have reported the mortality rate of mu- cormycosis between 40-80%, depending on the underlying conditions and extent of infection [22]. We had a signifi- cantly lower mortality rate of 16% in our study. It could be attributable to a high clinical suspicion, rapid diagnosis and intervention owing to being a referral center for otolaryngol- ogy patients. CAM indeed needs multidisciplinary manage- ment and thorough and serial examination. COVID-19-associated mucormycosis is a rising condition during the pandemic, and may be associated with less usual presentations; clinicians should be made aware of this un- usual presentation and incidence. It seems that the key to proper management of mucormycosis is early diagnosis and timely intervention, which could give the patient a better chance of survival. 5. Conclusion Rhinocerebral mucormycosis is one of the most important complications of COVID-19 patients, especially those with underlying diseases. It seems that the key to proper man- agement of mucormycosis is early diagnosis and timely in- tervention, which could give a patient a chance to live more. 6. Declarations 6.1. Acknowledgments The authors would like to sincerely thank the residents and fellowship students in ENT ward and operation room and anesthesiology technologists who helped in performing the surgeries of high-risk patients, peri-operation followings, and gathering the data. Also, we should express our sin- cere thanks to Dr. Hojjat Salmasian for English editing the manuscript. 6.2. Authors’ contributions Seyedhadi Samimi contributed in conceptualization, data collection, and collaborated in endoscopic surgeries. Shirin Irani contributed in study design, data collection, data inter- pretation, and collaborated in endoscopic surgeries and writ- ing the original draft of the manuscript. Mehrdad Hasibi con- tributed in conceptualization and performing the infectious consultations. Maral Seyedahadi contributed in conceptu- alization and neurologic consultations. Shahin Bastanine- jad contributed in conceptualization and collaborated in en- doscopic surgeries. Mohammadreza Firouzifar contributed in conceptualization and collaborated in endoscopic surg- eries. Sina Berijani and Samira Ahadi, otolaryngology resi- dents, contributed in conceptualisation, data collection, col- laboration in endoscopic surgeries and writing the original draft. Mojtaba Mohammadi Ardehali contributed in concep- tualization and collaborated in endoscopic surgeries. Reza Erfanian contributed in conceptualization and collaborated in endoscopic surgeries. Mohammad Ali Kazemi contributed in conceptualization and radiologic consultations. Afshar Etemadi-Aleagha contributed in conceptualization and col- laborated in anesthesia. Abolfazl Rahimi contributed in con- ceptualization and ophthalmologic consultation. Kourosh Karimi Yarandi contributed in conceptualization and neuro- surgical consultation. All authors read and approved the final manuscript. Shirin Irani had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis. 6.3. Funding and supports This project did not have any sources of financial support. 6.4. Conflict of interest The authors declare no conflict of interest in this study. 6.5. Data availability The Authors guarantee that data of the study are available and will be provided if anyone needs them. 6.6. Ethical considerations This study was approved by the ethical committee of Ami- ralam Hospital. Also, all the patients’ records are protected and confidential. References 1. deShazo, R.D., K. Chapin, and R.E. Swain, Fungal sinusi- tis. N Engl J Med, 1997. 337(4): p. 254-9. 2. Shafer, W., M. Hine, and B. Levy, Shafer’s Textbook of Oral Pathology. 5 [sup] th ed. 2006, Amsterdam: Elsevier Health Sciences. 3. Singh, J. and N.M. Prasanna, Phycomycosis in an appar- ently normal host. J Otolaryngol, 1977. 6(1): p. 37-42. 4. Sachdeva, K., Rhino-oculo Cerebral Mucormycosis with Multiple Cranial Nerve Palsy in Diabetic Patient: Review of Six Cases. Indian J Otolaryngol Head Neck Surg, 2013. 65(4): p. 375-9. 5. Hosseini, S.M. and P. Borghei, Rhinocerebral mucormy- cosis: pathways of spread. Eur Arch Otorhinolaryngol, 2005. 262(11): p. 932-8. 6. Kemper, J., et al., Recovery from rhinocerebral mucormy- cosis in a ketoacidotic diabetic patient: a case report. J Laryngol Otol, 1993. 107(3): p. 233-5. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem 9 Archives of Academic Emergency Medicine. 2022; 10(1): e66 7. Bigner, S., P. Burger, and P. Dubois, Diagnosis of cerebral mucormycosis by needle aspiration biopsy. A case report. Acta cytologica, 1982. 26(5): p. 699-704. 8. Saldanha, M., R. Reddy, and M.J. Vincent, Title of the Ar- ticle: Paranasal Mucormycosis in COVID-19 Patient. In- dian J Otolaryngol Head Neck Surg, 2021: p. 1-4. 9. Moorthy, A., et al., SARS-CoV-2, Uncontrolled Diabetes and Corticosteroids-An Unholy Trinity in Invasive Fungal Infections of the Maxillofacial Region? A Retrospective, Multi-centric Analysis. J Maxillofac Oral Surg, 2021. 20(3): p. 418-425. 10. Bayram, N., et al., Susceptibility of severe COVID-19 pa- tients to rhino-orbital mucormycosis fungal infection in different clinical manifestations. Jpn J Ophthalmol, 2021. 65(4): p. 515-525. 11. Patel, A., et al., Multicenter Epidemiologic Study of Coro- navirus Disease-Associated Mucormycosis, India. Emerg Infect Dis, 2021. 27(9): p. 2349-2359. 12. Ahmadikia, K., et al., The double-edged sword of sys- temic corticosteroid therapy in viral pneumonia: A case report and comparative review of influenza-associated mucormycosis versus COVID-19 associated mucormy- cosis. Mycoses, 2021. 64(8): p. 798-808. 13. Pakdel, F., et al., Mucormycosis in patients with COVID- 19: A cross-sectional descriptive multicentre study from Iran. Mycoses, 2021. 64(10): p. 1238-1252. 14. Raj, A., N. Kaur, and N. Kaur, Cavernous sinus thrombo- sis with central retinal artey occlusion in COVID-19: A case report and review of literature. Indian J Ophthalmol, 2021. 69(5): p. 1327-1329. 15. Khacha, A., et al., Cavernous sinus thrombosis in a COVID-19 patient: A case report. Radiol Case Rep, 2021. 16(3): p. 480-482. 16. Selvadurai, S. and J.S. Virk, Cavernous sinus thrombo- sis secondary to sphenoid mycetoma following COVID- 19 infection. Qjm, 2021. 114(8): p. 594-595. 17. Cancer-Perez, S., et al., Symptomatic Common Carotid Free-Floating Thrombus in a COVID-19 Patient, Case Re- port and Literature Review. Ann Vasc Surg, 2021. 73: p. 122-128. 18. Álvarez Moreno, Y., et al., Internal carotid artery throm- bosis in COVID 19. Colomb Med (Cali), 2020. 51(3): p. e504560. 19. Pisano, T.J., I. Hakkinen, and I. Rybinnik, Large Vessel Occlusion Secondary to COVID-19 Hypercoagulability in a Young Patient: A Case Report and Literature Review. J Stroke Cerebrovasc Dis, 2020. 29(12): p. 105307. 20. Little, J.S., et al., Invasive Fungal Carotiditis: A Rare Man- ifestation of Cranial Invasive Fungal Disease: Case Series and Systematic Review of the Literature. Open Forum In- fect Dis, 2019. 6(10): p. ofz392. 21. Patil, A., et al., Angioinvasive rhinocerebral mucormy- cosis with complete unilateral thrombosis of internal carotid artery-case report and review of literature. BJR Case Rep, 2016. 2(2): p. 20150448. 22. Cornely, O.A., et al., Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooper- ation with the Mycoses Study Group Education and Re- search Consortium. Lancet Infect Dis, 2019. 19(12): p. e405-e421. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: http://journals.sbmu.ac.ir/aaem Introduction Methods Results Discussion Conclusion Declarations References