Quantitative SARS-CoV-2 Serology in Children With Multisystem Inflammatory Syndrome (MIS-C).

Abstract

We aimed to measure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological responses in children hospitalized with multisystem inflammatory syndrome in children (MIS-C) compared with those with coronavirus disease 2019 (COVID-19), those with Kawasaki disease (KD), and hospitalized pediatric controls. From March 17, 2020, to May 26, 2020, we prospectively identified hospitalized children with MIS-C (<i>n</i> = 10), symptomatic COVID-19 (<i>n</i> = 10), and KD (<i>n</i> = 5) and hospitalized controls (<i>n</i> = 4) at Children's Healthcare of Atlanta. With institutional review board approval, we obtained prospective and residual blood samples from these children and measured SARS-CoV-2 spike receptor-binding domain (RBD) immunoglobulin M and immunoglobulin G (IgG), full-length spike IgG, and nucleocapsid protein antibodies using quantitative enzyme-linked immunosorbent assays and SARS-CoV-2 neutralizing antibodies using live-virus focus-reduction neutralization assays. We statistically compared the log-transformed antibody titers among groups and performed linear regression analyses. All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies (<i>R</i> ² = 0.956; <i>P</i> < .001), nucleocapsid protein antibodies (<i>R</i> ² = 0.846; <i>P</i> < .001), and neutralizing antibodies (<i>R</i> ² = 0.667; <i>P</i> < .001). Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG antibody titers (geometric mean titer 6800; 95% confidence interval 3495-13 231) than children with COVID-19 (geometric mean titer 626; 95% confidence interval 251-1563; <i>P</i> < .001), children with KD (geometric mean titer 124; 95% confidence interval 91-170; <i>P</i> < .001), and hospitalized controls (geometric mean titer 85; <i>P</i> < .001). All children with MIS-C also had detectable RBD immunoglobulin M antibodies, indicating recent SARS-CoV-2 infection. RBD IgG titers correlated with the erythrocyte sedimentation rate (<i>R</i> ² = 0.512; <i>P</i> < .046) and with hospital (<i>R</i> ² = 0.548; <i>P</i> = .014) and ICU lengths of stay (<i>R</i> ² = 0.590; <i>P</i> = .010). Quantitative SARS-CoV-2 serology may have a role in establishing the diagnosis of MIS-C, distinguishing it from similar clinical entities, and stratifying risk for adverse outcomes.