Cell
Volume 183, Issue 4, 12 November 2020, Pages 968-981.e7
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Article
The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19

https://doi.org/10.1016/j.cell.2020.09.016Get rights and content
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Highlights

  • Hyperinflammation in MIS-C differs from that of acute COVID-19

  • T cell subsets discriminate Kawasaki disease patients from MIS-C

  • IL-17A drives Kawasaki but not MIS-C hyperinflammation

  • Global profiling reveals candidate autoantibodies with pathogenic potential

Summary

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4–6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.

Keywords

COVID-19
multisystem inflammatory syndrome in children
MIS-C
SARS-CoV-2
Kawasaki disease
hyperinflammation in children
IL-17A
systems immunology
autoantibodies

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These authors contributed equally

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