Limited induction of SARS-CoV-2-specific T cell responses in children with multisystem inflammatory syndrome compared with COVID-19

• Type of Material: Article
• Authors: Ann Chahroudi, Emory University; Christina Rostad, Emory University; Vidisha Singh, Emory University; Veronica Obregon-Perko, Emory University; Stacey A Lapp, Emory University; Anna Marie Horner, Emory University; Alyssa Brooks, Emory University; Lisa Macoy, Emory University; Laila Hussaini, Emory University; Austin Lu, Emory University; Theda Gibson, Emory University; Guido Silvestri, Emory University; Alba Grifoni, La Jolla Institute for Immunology; Daniela Weiskopf, La Jolla Institute for Immunology; Alessandro Sette, La Jolla Institute for Immunology; Evan Anderson, Emory University
• Language: English
• Date: 2022-02-22
• Publisher: AMER SOC CLINICAL INVESTIGATION INC
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Singh et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.155145
• Title of Journal or Parent Work: JCI INSIGHT
• Volume: 7
• Issue: 4
• Grant/Funding Information: Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta and Emory University; FastGrant Program from Emergent Ventures at the Mercatus Center at George Mason University and Genentech
• Keywords: Life Sciences & Biomedicine; Medicine, Research & Experimental; Science & Technology; INFECTION; Research & Experimental Medicine
• Research Categories: Health Sciences, Pathology; Health Sciences, Medicine and Surgery

Abstract

Why multisystem inflammatory syndrome in children (MIS-C) develops after SARS-CoV-2 infection in a subset of children is unknown. We hypothesized that aberrant virus–specific T cell responses contribute to MIS-C pathogenesis. We quantified SARS-CoV-2–reactive T cells, serologic responses against major viral proteins, and cytokine responses from plasma and peripheral blood mononuclear cells in children with convalescent COVID-19, in children with acute MIS-C, and in healthy controls. Children with MIS-C had significantly lower virus-specific CD4+ and CD8+ T cell responses to major SARS-CoV-2 antigens compared with children convalescing from COVID-19. Furthermore, T cell responses in participants with MIS-C were similar to or lower than those in healthy controls. Serologic responses against spike receptor binding domain (RBD), full-length spike, and nucleocapsid were similar among convalescent COVID-19 and MIS-C, suggesting functional B cell responses. Cytokine profiling demonstrated predominant Th1 polarization of CD4+ T cells from children with convalescent COVID-19 and MIS-C, although cytokine production was reduced in MIS-C. Our findings support a role for constrained induction of anti–SARS-CoV-2–specific T cells in the pathogenesis of MIS-C.