Editors' ChoiceCOVID-19

MIS-Cing pieces of the puzzle

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Science Translational Medicine  30 Sep 2020:
Vol. 12, Issue 563, eabe6023
DOI: 10.1126/scitranslmed.abe6023

Abstract

Multisystem inflammatory syndrome in children associated with COVID-19 is distinct from other hyperinflammatory conditions in children.

Multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is a hyperinflammatory condition presenting in a subset of children weeks after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This condition has been reported in children across the world and is associated with high fever and organ dysfunction. Although the mechanism(s) underlying the development of MIS-C remains poorly understood, it has nevertheless drawn parallels to a similar autoimmune condition, Kawasaki disease. The latter is an autoimmune vasculitis with the highest incidence among children under five years of age.

To address this comparison, Consiglio et al. profiled the immune cells, cytokines, and antibodies in peripheral blood of pediatric patients with MIS-C and mild SARS-CoV-2 infection, comparing them with samples from a historical cohort of Kawasaki disease patients. In addition, the authors compared the profiles of these children with adults that were critically ill with SARS-CoV-2 infection. Among the peripheral blood immune cells profiled, the authors uncovered differences in the CD4+ T cell profile between children with MIS-C or Kawasaki disease. Interestingly, the authors reported reduced serum concentrations of interleukin-17A and other biomarkers of endothelial cell activation in patients with MIS-C, a cytokine that has been previously associated with Kawasaki disease. Surprisingly, serum concentrations of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor α were not elevated in children with MIS-C. Although the authors tested a range of autoantibodies in serum isolated from children diagnosed with each condition, they did not see any specific signals distinguishing MIS-C from Kawasaki disease.

Although the analyses in this study cannot establish the mechanism(s) by which MIS-C develops, it does provide some rationale to support repurposing treatment strategies employed for other autoimmune conditions. Fortunately, MIS-C has responded to a combination of anti-inflammatory agents, including corticosteroids and IL-1 antagonists. As with many other studies related to COVID-19 disease in children, this study is limited by small samples size due to the overall rarity of this complication. However, the translational relevance of this study lies in highlighting the differences between MIS-C and Kawasaki disease. Although MIS-C and Kawasaki disease are superficially similar conditions, the differences reported in this study support the use of caution when applying therapeutic strategies for Kawasaki disease to treatment of MIS-C.

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