Abstract

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.

Highlights

  • The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) first emerged in Wuhan in December 2019 (Huang et al, 2020) and spread rapidly to a number of countries and, in particular, to Europe and the northern regions of Italy in the early weeks of February 2020

  • We compare these children with 28 children presenting with Kawasaki disease prior to the COVID-19 pandemic (March 2017 to May 2019)

  • No significant sex-differences were found among the groups of children. Both multisystem inflammatory syndrome in children (MIS-C) and CoV-2+ children presented with lower white blood cell counts (WBC) as compared to patients with Kawasaki disease and healthy children (Olin et al, 2018; Figure 1B)

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Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) first emerged in Wuhan in December 2019 (Huang et al, 2020) and spread rapidly to a number of countries and, in particular, to Europe and the northern regions of Italy in the early weeks of February 2020. The view that COVID-19 disease course is always mild in children is challenged by recent reports of children presenting with a rare, but very severe hyperinflammatory syndrome in the United Kingdom (Riphagen et al, 2020; Whittaker et al, 2020), Italy (Verdoni et al, 2020), Spain (Moraleda et al, 2020), and New York City (Cheung et al, 2020). In these case series, children present with high fevers, and a variable number of symptoms previously associated with Kawasaki disease such as conjunctivitis, lymphadenopathy, mucocutaneous rash, and coronary artery dilation, and in the most severe cases, cardiovascular shock, encephalitis, and multiple organ failure

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