The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recovery
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
Affiliations
Eleni Syrimi
Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK
Eanna Fennell
Health Research Institute and the Bernal Institute, University of Limerick, Limerick, Ireland
Alex Richter
Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK
Pavle Vrljicak
Warwick Medical School, University of Warwick, Coventry, UK
Richard Stark
Bioinformatics Research Technology Platform, University of Warwick, Coventry, UK
Sascha Ott
Warwick Medical School, University of Warwick, Coventry, UK; Bioinformatics Research Technology Platform, University of Warwick, Coventry, UK
Paul G. Murray
Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK; Health Research Institute and the Bernal Institute, University of Limerick, Limerick, Ireland
Eslam Al-Abadi
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Ashish Chikermane
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Pamela Dawson
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Scott Hackett
Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Deepthi Jyothish
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Hari Krishnan Kanthimathinathan
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Sean Monaghan
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK
Prasad Nagakumar
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
Barnaby R. Scholefield
Birmingham Women's and Children's NHS Foundation Trust, Birmingham, UK; Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
Steven Welch
Heartlands Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Naeem Khan
Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK
Sian Faustini
Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK
Kate Davies
Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK
Wioleta M. Zelek
Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, UK
Pamela Kearns
NIHR Birmingham Biomedical Research Centre and Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK; Corresponding author
Graham S. Taylor
Institute of Immunology and Immunotherapy, University of Birmingham, B15 2TT Birmingham, UK; Corresponding author
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.
