Pre–Covid-19, SARS-CoV-2–Negative Multisystem Inflammatory Syndrome in Children

This correspondence in The New England Journal of Medicine documents cases of multisystem inflammatory syndrome in children (MIS-C) predating the Covid-19 pandemic and unlinked to SARS-CoV-2. Through retrospective T-cell receptor repertoire analyses of hospitalized children (2006–2018), researchers identified a distinctive VB21.3+ CD4+/CD8+ T-cell expansion — a hallmark of MIS-C — in six patients lacking SARS-CoV-2 infection. One patient showed evidence of HCoV-229E infection, suggesting alternative viral triggers. These findings challenge the notion that SARS-CoV-2 is necessary for MIS-C pathogenesis. The study highlights immunologic parallels across MIS-C, Kawasaki’s disease, and toxic shock syndrome, reinforcing the urgency of further research on superantigen-driven immune activation and targeted therapies.

This correspondence in The New England Journal of Medicine documents cases of multisystem inflammatory syndrome in children (MIS-C) predating the Covid-19 pandemic and unlinked to SARS-CoV-2. Through retrospective T-cell receptor repertoire analyses of hospitalized children (2006–2018), researchers identified a distinctive VB21.3+ CD4+/CD8+ T-cell expansion — a hallmark of MIS-C — in six patients lacking SARS-CoV-2 infection. One patient showed evidence of HCoV-229E infection, suggesting alternative viral triggers. These findings challenge the notion that SARS-CoV-2 is necessary for MIS-C pathogenesis. The study highlights immunologic parallels across MIS-C, Kawasaki’s disease, and toxic shock syndrome, reinforcing the urgency of further research on superantigen-driven immune activation and targeted therapies.