The Innate and Adaptive Immune Landscape of SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children (MIS-C) from Acute Disease to Recovery

Abstract

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. MIS-C has overlapping clinical features with Kawasaki Disease (KD), a rare childhood vasculitis, but whether these diseases share underpinning immunological perturbations is unknown. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and double-negative B-cells; and increased cytokine levels. Post treatment samples from the same patients, taken when symptoms were resolving, identified recovery-associated immune features including CD163+ monocytes, emergence of a new population of immature neutrophils and, in some patients, a transient increase in arginase. Our data show MIS-C and KD share substantial immunopathology during the acute and recovery stages of disease and identify potential new mechanisms of action for IVIG, a widely used anti-inflammatory drug used to treat MIS-C, KD and other inflammatory diseases.