iScience
Volume 24, Issue 11, 19 November 2021, 103215
Journal home page for iScience

Article
The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery

https://doi.org/10.1016/j.isci.2021.103215Get rights and content
Under a Creative Commons license
open access

Highlights

  • Granulocyte frequency correlates with MIS-C disease severity at presentation

  • Recovering patients have increased CD163 on monocytes and new atypical neutrophils

  • Cytokine profile of acute MIS-C suggests inhibiting IL6 rather than IL1 or TNF

  • Raised plasma C5b-9 identifies complement inhibitors as potential MIS-C therapy

Summary

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, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential 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.

Subject areas

Genomics
Immune response
Immune system disorder
Immunology

Data and code availability

Raw and processed single cell RNA-seq data have been deposited online in GEO and are publicly available (www.ncbi.nlm.nih.gov/geo/ accession number GSE183716).

Cited by (0)

11

These authors contributed equally

12

Lead contact