Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019
Stacey A. Lapp, Joseph Y. Abrams, Austin Lu, Laila Hussaini, Carol Kao, David A. Hunstad, Robert B. Rosenberg, Marc J. Zafferani, Kaleo Ede, Wassim Ballan, Federico R. Laham, Yajira Beltran, Hui‐Mien Hsiao, Whitney Sherry, Elan Jenkins, Kaitlin Jones, Anna M. Horner, Alyssa D. Brooks, Bobbi Bryant, Lu Meng, Teresa A. Hammett, Matthew E. Oster, Sapna Bamrah-Morris, Shana Godfred‐Cato, Ermias D. Belay, Ann Chahroudi, Evan J. Anderson, Preeti Jaggi, Christina A. Rostad
Abstract
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.