Single-cell RNA-seq reveals profound monocyte changes in Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 infection (PIMS-TS)

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. MIS-C therapy is largely based on KD treatment protocols but whether these diseases share underpinning immunological perturbations is unknown. We performed deep immune profiling on blood samples from healthy children and patients with MIS-C or KD. Acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells; increased frequencies of B-cell plasmablasts and CD27-IgD-double-negative B-cells; and increased levels of pro-inflammatory (IL6, IL18, IP10, MCP1) but also anti-inflammatory (IL-10, IL1-RA, sTNFR1, sTNFR2) cytokines. Increased neutrophil count correlated with inflammation,cardiac dysfunction and disease severity. Two days after intravenous immunoglobulin (IVIG) treatment, MIS-C patients had increased CD163 expression on monocytes, expansion of a novel population of immature neutrophils, and decreased levels of pro- and anti-inflammatory cytokines in the blood accompanied by a transient increase in arginase in some patients. Our data show MIS-C and KD share substantial immunopathology 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.