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

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

doi:10.1172/jci.insight.155145

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.

Highlights

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare and severe complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)infection
MIS-C is characterized by serious illness leading to hospitalization, fever, elevated markers of inflammation, multisystem organ involvement, and evidence of infection with SARS-CoV-2 based on room temperature (RT)-PCR, serology, or antigen test, or epidemiologic exposure to persons with COVID-19 [1]
We collected convalescent blood samples from the COVID-19 participants to approximate a similar interval from SARS-CoV-2 infection as presumed for the MIS-C cohort

Summary

Introduction

MIS-C is characterized by serious illness leading to hospitalization, fever, elevated markers of inflammation, multisystem organ involvement, and evidence of infection with SARS-CoV-2 based on RT-PCR, serology, or antigen test, or epidemiologic exposure to persons with COVID-19 [1]. The specific mechanisms leading to MIS-C following SARS-CoV-2 infection are unknown, and it can be difficult to distinguish causative factors from those occurring as a consequence of the hyperinflammatory state. T and B cell lymphopenia is a prominent feature of MIS-C [8], with expansion of a subset of T-cells utilizing specific TCR Vb chains, leading to the hypothesis that the presence of a viral reservoir with ongoing viral replication or a viral superantigen drives both immune system dysfunction and immunopathology. It is likely that multiple factors, acting in concert, influence the development of MIS-C

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Results

Conclusion