Serology in Children with Multisystem Inflammatory Syndrome (MIS-C) associated with COVID-19

ObjectivesWe aimed to measure SARS-CoV-2 serologic responses in children hospitalized with multisystem inflammatory syndrome (MIS-C) compared to COVID-19, Kawasaki Disease (KD) and other hospitalized pediatric controls. MethodsFrom March 17, 2020 - May 26, 2020, we prospectively identified hospitalized children at Childrens Healthcare of Atlanta with MIS-C (n=10), symptomatic PCR-confirmed COVID-19 (n=10), KD (n=5), and hospitalized controls (n=4). With IRB approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike (S) receptor binding domain (RBD) IgM and IgG binding antibodies by quantitative ELISA and SARS-CoV-2 neutralizing antibodies by live-virus focus reduction neutralization assay. We statistically compared the log-transformed antibody titers among groups and performed correlation analyses using linear regression. ResultsAll children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated strongly with neutralizing antibodies (R2=0.667, P<0.001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer [GMT] 6800, 95%CI 3495-13231) than children with COVID-19 (GMT 626, 95%CI 251-1563, P<0.001), children with KD (GMT 124, 95%CI 91-170, P<0.001) and other hospitalized pediatric controls (GMT 85 [all below assay limit of detection], P<0.001). All children with MIS-C also had detectable RBD IgM antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with erythrocyte sedimentation rate (ESR) (R2=0.512, P<0.046) and with hospital and ICU lengths of stay (R2=0.590, P=0.010). ConclusionQuantitative SARS-CoV-2 RBD antibody titers may have a role in establishing the diagnosis of MIS-C, distinguishing it from other similar clinical entities, and stratifying risk for adverse outcomes. Table of Contents SummaryChildren with MIS-C have high antibody titers to the SARS-CoV-2 spike protein receptor binding domain, which correlate with neutralization, systemic inflammation, and clinical outcomes. Whats Known on This SubjectAlthough the clinical features of a multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 have been recently described, the serologic features of MIS-C are unknown. What This Study AddsIn this case series, all hospitalized children with MIS-C had significantly higher SARS-CoV-2 binding and neutralizing antibodies than children with COVID-19 or Kawasaki Disease. SARS-CoV-2 antibodies correlated with metrics of systemic inflammation and clinical outcomes, suggesting diagnostic and prognostic value.