Open Forum Infect Dis . Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019

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Open Forum Infect Dis


. 2022 Feb 24;9(3):ofac070.
doi: 10.1093/ofid/ofac070. eCollection 2022 Mar.
Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019


Stacey A Lapp ^{1 2} , Joseph Abrams ³ , Austin T Lu ^{1 2} , Laila Hussaini ^{1 2} , Carol M Kao ⁴ , David A Hunstad ⁴ , Robert B Rosenberg ^{5 6} , Marc J Zafferani ^{5 6} , Kaleo C Ede ^{6 7} , Wassim Ballan ^{6 8} , Federico R Laham ⁹ , Yajira Beltran ⁹ , Hui-Mien Hsiao ^{1 2} , Whitney Sherry ^{1 2} , Elan Jenkins ^{1 2} , Kaitlin Jones ² , Anna Horner ^{1 2} , Alyssa Brooks ^{1 2} , Bobbi Bryant ^{3 10} , Lu Meng ^{3 11} , Teresa A Hammett ³ , Matthew E Oster ^{1 2 3} , Sapna Bamrah-Morris ³ , Shana Godfred-Cato ³ , Ermias Belay ³ , Ann Chahroudi ^{1 2} , Evan J Anderson ^{1 2 12} , Preeti Jaggi ^{1 2} , Christina A Rostad ^{1 2}



Affiliations

• PMID: 35237703
• PMCID: PMC8883592
• DOI: 10.1093/ofid/ofac070

Abstract

Background: The serologic and cytokine responses of children hospitalized with multisystem inflammatory syndrome (MIS-C) vs coronavirus disease 2019 (COVID-19) are poorly understood.
Methods: We performed a prospective, multicenter, cross-sectional study of hospitalized children who met the Centers for Disease Control and Prevention case definition for MIS-C (n = 118), acute COVID-19 (n = 88), or contemporaneous healthy controls (n = 24). We measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) immunoglobulin G (IgG) titers and cytokine concentrations in patients and performed multivariable analysis to determine cytokine signatures associated with MIS-C. We also measured nucleocapsid IgG and convalescent RBD IgG in subsets of patients.
Results: Children with MIS-C had significantly higher SARS-CoV-2 RBD IgG than children with acute COVID-19 (median, 2783 vs 146; P < .001), and titers correlated with nucleocapsid IgG. For patients with MIS-C, RBD IgG titers declined in convalescence (median, 2783 vs 1135; P = .010) in contrast to patients with COVID-19 (median, 146 vs 4795; P < .001). MIS-C was characterized by transient acute proinflammatory hypercytokinemia, including elevated levels of interleukin (IL) 6, IL-10, IL-17A, and interferon gamma (IFN-γ). Elevation of at least 3 of these cytokines was associated with significantly increased prevalence of prolonged hospitalization ≥8 days (prevalence ratio, 3.29 [95% CI, 1.17-9.23]).
Conclusions: MIS-C was associated with high titers of SARS-CoV-2 RBD IgG antibodies and acute hypercytokinemia with IL-6, IL-10, IL-17A, and IFN-γ.

Keywords: COVID-19; MIS-C; PIMS; SARS-CoV-2; children; cytokines; serology.