JCI Insight (Feb 2022)

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

  • Vidisha Singh,
  • Veronica Obregon-Perko,
  • Stacey A. Lapp,
  • Anna Marie Horner,
  • Alyssa Brooks,
  • Lisa Macoy,
  • Laila Hussaini,
  • Austin Lu,
  • Theda Gibson,
  • Guido Silvestri,
  • Alba Grifoni,
  • Daniela Weiskopf,
  • Alessandro Sette,
  • Evan J. Anderson,
  • Christina A. Rostad,
  • Ann Chahroudi

Journal volume & issue
Vol. 7, no. 4

Abstract

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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.

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