1. The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery
- Author
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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, and Graham S. Taylor
- Subjects
Genomics ,Immune response ,Immune system disorder ,Immunology ,Science - 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.
- Published
- 2021
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