The immune landscape of SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C) from acute disease to recovery

Syrimi, Eleni, Fennell, Eanna, Richter, Alex, Vrljicak, Pavle, Stark, Richard, Ott, Sascha, Murray, Paul G., Al-Abadi, Eslam, Chikermane, Ashish, Dawson, Pamela, Hackett, Scott, Jyothish, Deepthi, Kanthimathinathan, Hari Krishnan, Monaghan, Sean, Nagakumar, Prasad, Scholefield, Barnaby R., Welch, Steven, Khan, Naeem, Faustini, Sian, Davies, Kate ORCID: https://orcid.org/0000-0002-9807-1231, Zelek, Wioleta M., Kearns, Pamela and Taylor, Graham S. 2021. The immune landscape of SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C) from acute disease to recovery. iScience 24 (11) , 103215. 10.1016/j.isci.2021.103215

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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, 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	Creative Commons Attribution 4.0 International (CC BY 4.0)
Publisher:	Cell Press
ISSN:	2589-0042
Date of First Compliant Deposit:	18 November 2021
Date of Acceptance:	26 September 2021
Last Modified:	20 May 2023 21:44
URI:	https://orca.cardiff.ac.uk/id/eprint/145592

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