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Single cell RNA sequencing and TCR repertoire analysis of MIS-C affected patients versus healthy controls and severe adult COVID-19

ABSTRACT: In rare instances, pediatric SARS-CoV2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with that of severe COVID-19. MIS-C does not result in pneumocyte damage but is associated with vascular endothelitis, gastrointestinal epithelial injury and endotoxemia. In MIS-C, IFN dominates the inflammatory signature in contrast to type I interferons in severe COVID-19. While HLA-DRlo classical monocytes dominate severe COVID-19, patrolling monocyte activation characterize MIS-C. TIM-3 expression on activated CD4/CD8  T cells and on CD57+ NK cells is a distinctive MIS-C feature. In all MIS-C patients, single cell TCR profiling demonstrates a skewed TCR repertoire enriched for TRBV11-2 and a superantigenic signature which is absent in severe COVID-19. Using NicheNet, we confirm IFN as a central cytokine in the communication between activated T cells, NK cells and patrolling monocytes. Rapid normalization of IFN, TIM-3 loss on T cells and patrolling monocytes contraction upon treatment highlight their potential role in MIS-C immunopathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184330 | GEO | 2021/12/09

REPOSITORIES: GEO

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