학술논문
The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery
Document Type
article
Author
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 Davies; Wioleta M. Zelek; Pamela Kearns; Graham S. Taylor
Source
iScience, Vol 24, Iss 11, Pp 103215- (2021)
Subject
Language
English
ISSN
2589-0042
Abstract
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.