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

Eleni Syrimi, Eanna Fennell, Alex Richter, Pavle Vrljicak, Richard Stark, Sascha Ott, Paul G Murray, Eslam Al-Abadi, Ashish Chikermane, Pamela Dawson, Scott Hackett, Deepthi Jyothish, Hari Krishnan Kanthimathinathan, Sean Monaghan, Prasad Nagakumar, Barnaby R Scholefield, Steven Welch, Naeem Khan, Sian Faustini, Kate DaviesWioleta M Zelek, Pamela Kearns, Graham S Taylor

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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 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 IL6 may be preferable to IL1 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.

Original languageEnglish
Article number103215
JournaliScience
Volume24
Issue number11
Early online date2 Oct 2021
DOIs
Publication statusPublished - 19 Nov 2021

Bibliographical note

© 2021 The Authors.

Keywords

  • Genomics
  • Immune response
  • Immune system disorder
  • Immunology

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