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.
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Authors | 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 | JCI insight
(JCI Insight)
Vol. 7
Issue 4
(02 22 2022)
ISSN: 2379-3708 [Electronic] United States |
PMID | 35044955
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Topics |
- Adolescent
- COVID-19
(complications, immunology)
- Child
- Child, Preschool
- Female
- Humans
- Male
- SARS-CoV-2
(immunology)
- Systemic Inflammatory Response Syndrome
(immunology)
- T-Lymphocytes
(immunology)
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