Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

Results of Testing Children for Severe Acute Respiratory Syndrome Coronavirus-2 Through a Community-based Testing Site.

OBJECTIVE: To describe the demographics, clinical features, and test results of children referred from their primary provider for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the community setting. STUDY DESIGN: Retrospective cross-sectional study of children ≤22 years of age who were tested for SARS-CoV-2 at a community-based specimen collection site in Washington, DC, affiliated with a large children's hospital between March 21 and May 16, 2020. RESULTS: Of the 1445 patients tested at the specimen collection site for SARS-CoV-2 virus, 408 (28.2%) had a positive polymerase chain reaction test. The daily positivity rate increased over the study period, from 5.4% during the first week to a peak of 47.4% (Ptrend < .001). Patients with fever (aOR, 1.7; 95% CI, 1.3-2.3) or cough (aOR, 1.4; 95% CI, 1.1-1.9) and those with known contact with someone with confirmed SARS-CoV-2 infection (aOR, 1.6; 95% CI, 1.0-2.4.) were more likely have a positive test, but these features were not highly discriminating. CONCLUSIONS: In this cohort of mildly symptomatic or well children and adolescents referred to a community drive-through/walk-up SARS-CoV-2 testing site because of risk of exposure or clinical illness, 1 in 4 patients had a positive test. Children and young adults represent a considerable burden of SARS-CoV-2 infection. Assessment of their role in transmission is essential to implementing appropriate control measures.

Kinetics of Viral Clearance and Antibody Production Across Age Groups in Children with Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

OBJECTIVES: To improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. STUDY DESIGN: This retrospective analysis of children tested for SARS-CoV-2 by reverse transcription (RT) polymerase chain reaction (PCR) and immunoglobulin G antibody at a quaternary-care, free-standing pediatric hospital between March 13, 2020, and June 21, 2020, included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity. RESULTS: The rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and time from RT-PCR positivity to negativity was 25 days. Of note, patients aged 6 through 15 years demonstrated a longer time of RT-PCR positivity to negativity, compared with patients aged 16 through 22 years (median 32 vs 18 days, P = .015). Median time to seropositivity, by chemiluminescent testing, from RT-PCR positivity was 18 days, whereas median time to reach adequate levels of neutralizing antibodies (defined as comparable with 160 titer by plaque reduction neutralization testing) was 36 days. CONCLUSIONS: The majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. It is unknown whether this correlates with persistent infectivity. Only 17 of 33 patients demonstrated adequate neutralizing antibodies during the time frame of specimen collection. It remains unknown whether immunoglobulin G antibody against spike structured proteins correlates with immunity, and how long antibodies and potential protection persist.

Severe Coronavirus Disease-2019 in Children and Young Adults in the Washington, DC, Metropolitan Region.

Despite worldwide spread of severe acute respiratory syndrome coronavirus-2, few publications have reported the potential for severe disease in the pediatric population. We report 177 infected children and young adults, including 44 hospitalized and 9 critically ill patients, with a comparison of patient characteristics between infected hospitalized and nonhospitalized cohorts, as well as critically ill and noncritically ill cohorts. Children <1 year and adolescents and young adults >15 years of age were over-represented among hospitalized patients (P = .07). Adolescents and young adults were over-represented among the critically ill cohort (P = .02).