Abstract
SUMMARYMultisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
Publisher
Cold Spring Harbor Laboratory
Reference49 articles.
1. Feldstein, L.R. , et al. Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med (2020).
2. COVID-19 and Kawasaki Disease: Novel Virus and Novel Case
3. Riphagen, S. , Gomez, X. , Gonzalez-Martinez, C. , Wilkinson, N. & Theocharis, P . Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet (2020).
4. Multisystem Inflammatory Syndrome with Features of Atypical Kawasaki Disease during COVID-19 Pandemic
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