Serologic and Cytokine Signatures in Children With Multisystem Inflammatory Syndrome and Coronavirus Disease 2019. (24th February 2022)

• Record Type: Journal Article
• Authors: Lapp, Stacey A; Abrams, Joseph; Lu, Austin T; Hussaini, Laila; Kao, Carol M; Hunstad, David A; Rosenberg, Robert B; Zafferani, Marc J; Ede, Kaleo C; Ballan, Wassim; Laham, Federico R; Beltran, Yajira; Hsiao, Hui-Mien; Sherry, Whitney; Jenkins, Elan; Jones, Kaitlin; Horner, Anna; Brooks, Alyssa; Bryant, Bobbi; Meng, Lu; Hammett, Teresa A; Oster, Matthew E; Bamrah-Morris, Sapna; Godfred-Cato, Shana; Belay, Ermias; Chahroudi, Ann; Anderson, Evan J; Jaggi, Preeti; Rostad, Christina A
• Is Part Of: Open forum infectious diseases. Volume 9:Number 3(2022)
• Publication Date: 2022-02-24
• Subjects: children -- COVID-19 -- cytokines -- MIS-C -- PIMS -- SARS-CoV-2 -- serology; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac070
• Languages: English
• ISSNs: 2328-8957

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.