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

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. 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. 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. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL6 may be preferable to IL1 or TNF-a. We identified potential new mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C, suggesting complement inhibitors could be used to treat the disease.Funding Information Birmingham Women’s and Children’s Hospital Charity funded the single cell RNA sequencing analysis. No other external funding was received. Declaration of Interests None declared.Ethics Approval Statement Reviewed and approved by South of Birmingham Research Ethics Committee (REC 17/WM/0453, IRAS 233593).