key: cord-322435-c88tkbnz
authors: Rekhtman, Sergey; Tannenbaum, Rachel; Strunk, Andrew; Birabaharan, Morgan; Wright, Shari; Garg, Amit
title: Mucocutaneous Disease and Related Clinical Characteristics in Hospitalized Children and Adolescents with COVID-19 and MIS-C
date: 2020-10-24
journal: J Am Acad Dermatol
DOI: 10.1016/j.jaad.2020.10.060
sha: 
doc_id: 322435
cord_uid: c88tkbnz

Background Little is known about mucocutaneous disease in acutely-ill children and adolescents with COVID-19 and MIS-C. Objective To characterize mucocutaneous disease and its relation to clinical course among hospitalized patients with COVID-19 and MIS-C. Methods Descriptive cohort study of prospectively and consecutively hospitalized eligible patients between May 11, 2020 and June 5, 2020. Results In COVID-19 patients, 4/12 (33%) had rash and/or mucositis, including erythema, morbilliform pattern, and lip mucositis. In MIS-C patients, 9/19 (47%) had rash and/or mucositis, including erythema, morbilliform, retiform purpura, targetoid and urticarial patterns, along with acral edema, lip mucositis, tongue papillitis, and conjunctivitis. COVID-19 patients with rash had less frequent respiratory symptoms, PICU admission, and invasive ventilation, as well as shorter stay (vs COVID-19 without rash). MIS-C patients with rash had less frequent PICU admission, shock, ventilation, as well as lower levels of CRP, ferritin, D-dimer, and troponin (vs MIS-C without rash). Neutrophil-to-lymphocyte ratio was similar for patients with and without rash in both groups. None of the MIS-C patients met criteria for Kawasaki disease. Limitations Small sample sizes. Conclusions Mucocutaneous disease is common among children and adolescents with COVID-19 and MIS-C. Laboratory trends observed in patients with rash may prognosticate a less severe course.

Coronavirus disease 2019 has variability within its constellation of findings among 73 children and adolescents. [1] [2] [3] [4] [5] In addition to fever and respiratory symptoms, pediatric patients infected with 74 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen in COVID-19, also 75 develop eruptions and mucositis. Yet little is understood about the morphologic spectrum of 76 mucocutaneous disease and its relation to outcomes among acutely-ill children and adolescents with 77 COVID-19, or its presumed sequela, multisystem inflammatory syndrome in children (MIS-C). The New 78

York metropolitan area was an epicenter for the pandemic in the United States, 6 and this provided an 79 opportunity to characterize mucocutaneous disease in pediatric hospitalized patients with COVID-19 and 80 MIS-C. The purpose of this study was to estimate prevalence of integumentary findings in hospitalized 81 patients with COVID-19 and MIS-C, to characterize their morphologic patterns, to evaluate whether rash 82

prognosticates clinical course, and to determine how closely features in MIS-C align with Kawasaki 83 Disease (KD). 84

This study was performed at Cohen Children's Hospital (Northwell Health), a tertiary hospital 86 located in Queens, New York. The study sample consisted of all hospitalized patients between May 11, 87 2020 and June 5, 2020 who were aged ≤18 years and who were suspected of having COVID-19 or MIS-88 C. Criteria for confirming the diagnosis of MIS-C included age <21 years, fever for ≥24 hours, clinically 89 severe illness requiring hospitalization, multisystem organ involvement, no alternative plausible 90 diagnosis, and exposure to a suspected or confirmed COVID-19 case or positive SARS-CoV-2 infection 91 by PCR/serology testing. 7 The sample was limited to patients who had 1) diagnosis of MIS-C based on all 92 six criteria above, and this group comprised the MIS-C cohort; or 2) positive COVID-19 PCR test among 93 those not meeting the definition of MIS-C, and this group comprised the COVID-19 cohort. presence of at least one COVID-19-related rash. We categorized COVID-19 and MIS-C patients 104 separately because these diseases have different clinical characteristics and disease courses, and because 105 MIS-C is considered to be a later, non-infectious complication of COVID-19. 106

Given the anticipated sample size, and consequently low statistical power, the intent of our 108 analysis was descriptive and hypothesis generating. Medians (IQR) were used to describe continuous 109 variables, and frequencies (percentages) were used to describe categorical variables. This study was 110 approved by the institutional review board at the Feinstein Institutes of Medical Research at Northwell 111

Of 39 hospitalized pediatric patients identified as possible COVID-19 or MIS-C during the study 114 period, 31 were eligible for inclusion. Six patients did not test positive for SARS-CoV-2 PCR and were 115 also ruled out for MIS-C prior to discharge. Others excluded were one child whose family deferred skin 116 examination, and one newborn having limb necrosis with negative SARS-CoV-2 PCR and IgM antibody, 117 who was felt to have fetal compartment syndrome. Demographic characteristics for 12 patients classified 118 as COVID-19 and 19 patients classified as MIS-C are listed in Table 1 . Those with rash were younger. (Table I) . Only three of 12 (25%) were febrile (≥100.4°F) during 122

Type and frequencies of morphologic patterns observed in patients with COVID-19 are described 124

in Table 1 . None of the hospitalized COVID-19 patients with rash had pernio-like lesions of the toes or 125 fingers, and none had conjunctivitis. Locations and frequencies of mucocutaneous eruptions in patients 126

with COVID-19 are described in Figure 1 . 127 Compared to COVID-19 patients without rash, those with rash were observed to have less 128 frequent respiratory symptoms, admission to the pediatric intensive care unit (PICU), and ventilation, as 129 well as shorter length of hospital stay. Maximum neutrophil-to-lymphocyte ratio (NLR) observed during 130 hospitalization was similar for patients with and without rash. (Table II) 131

In patients with MIS-C, 9/19 (47%) had rash and/or mucositis. (Figure 2 ; Supplemental Figure  133 2) All 19 patients (100%) were febrile during hospitalization. 134

Morphologic patterns were heterogeneous. (Table I ) Lip fissuring or cracking was present in 135 44% (4/9), while papillitis of the tongue was present in 22% (2/9). Conjunctivitis was present in 22% 136

(2/9) of patients with rash. Locations and frequencies of mucocutaneous eruptions in patients with MIS-C 137 are described in Figure 1 . 138 Compared to MIS-C patients without rash, those with rash were observed to have less frequent 139 PICU admission, shock, and requirement for invasive mechanical ventilation. Patients with rash also had 140 lower levels of inflammatory markers. Maximum NLR observed during hospitalization was similar for 141 patients with and without rash. (Table II) We observed that presence of rash appears to prognostic a less severe clinical course. Finally, we 157 observed that MIS-C and KD may be more dissimilar the presently postulated. and adolescents, and the basis for preferential involvement of skin, warrants further study. 180

The NLRs were similar between COVID-19 patients with and without rash, as well as between 181

MIS-C patients with and without rash. We did however observe higher NLR in MIS-C patients as 182 compared with COVID-19 patients, and this may prove to be a useful differentiating marker. In adults, 183 NLR has been observed to distinguish mild from severe cases of COVID-19. May and June of 2020 in the New York metropolitan area. As such, we had inadequate power to perform 196 hypothesis tests and we cannot rule out that differences observed between groups were due to chance. 197

However, the finding of less severe course was observed across several indicators among both and MIS-C patients with rash. Pathology was not obtained as there was no clear indication this could 199 specify diagnoses or change the courses of care. 

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