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

Christina A. Rostad, Ann Chahroudi, Grace Mantus, Stacey A. Lapp, Mehgan Teherani, Lisa Macoy, Keiko M. Tarquinio, Rajit K. Basu, Carol Kao, W. Matthew Linam, Matthew G. Zimmerman, Pei Yong Shi, Vineet D. Menachery, Matthew E. Oster, Srilatha Edupuganti, Evan J. Anderson, Mehul S. Suthar, Jens Wrammert, Preeti Jaggi

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104 Scopus citations

Abstract

OBJECTIVES: 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. METHODS: From March 17, 2020, to May 26, 2020, we prospectively identified hospitalized children with MIS-C (n = 10), symptomatic COVID-19 (n = 10), and KD (n = 5) and hospitalized controls (n = 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. RESULTS: All children with MIS-C had high titers of SARS-CoV-2 RBD IgG antibodies, which correlated with full-length spike IgG antibodies (R2 = 0.956; P, .001), nucleocapsid protein antibodies (R2 = 0.846; P, .001), and neutralizing antibodies (R2 = 0.667; P, .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; P, .001), children with KD (geometric mean titer 124; 95% confidence interval 91–170; P, .001), and hospitalized controls (geometric mean titer 85; P, .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 (R2 = 0.512; P, .046) and with hospital (R2 = 0.548; P = .014) and ICU lengths of stay (R2 = 0.590; P = .010). CONCLUSIONS: 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.

Original languageEnglish
Article numbere2020018242
JournalPediatrics
Volume146
Issue number6
DOIs
StatePublished - Dec 1 2020

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