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, 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:	24 Nov 2021 12:15
URI:	https://orca.cardiff.ac.uk/id/eprint/145592

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