The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery
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.
Author
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
Taylor, Graham S
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
Taylor, Graham S
Citations
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Date
2021-10-02
Type
Article
Subject
Microbiology. Immunology
Collections
Citation
Syrimi E, Fennell E, Richter A, Vrljicak P, Stark R, Ott S, Murray PG, Al-Abadi E, Chikermane A, Dawson P, Hackett S, Jyothish D, Kanthimathinathan HK, Monaghan S, Nagakumar P, Scholefield BR, Welch S, Khan N, Faustini S, Davies K, Zelek WM, Kearns P, Taylor GS. The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery. iScience. 2021 Nov 19;24(11):103215. doi: 10.1016/j.isci.2021.103215. Epub 2021 Oct 2
Journal / Source Title
iScience
DOI
10.1016/j.isci.2021.103215
PMID
34632327
Publisher
Cell Press
Publisher’s URL
http://www.cell.com/iscience/home