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The Innate and Adaptive Immune Landscape of SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children (MIS-C) From Acute Disease to Recovery

55 Pages Posted: 19 Jul 2021 Publication Status: Published

See all articles by Eleni Syrimi

Eleni Syrimi

University of Birmingham - Institute of Immunology and Immunotherapy

Eanna Fennell

University of Limerick - Health Research Institute and the Bernal Institute

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Pavle Vrljicak

University of Warwick - Division of Biomedical Sciences

Richard Stark

University of Warwick - Bioinformatics Research Technology Platform

Sascha Ott

University of Warwick - Division of Biomedical Sciences

Paul G. Murray

University of Limerick - Health Research Institute and the Bernal Institute

Eslam Al-Abadi

Birmingham Women’s and Children’s NHS Foundation Trust

Ashish Chikermane

Birmingham Women’s and Children’s NHS Foundation Trust

Pamela Dawson

Birmingham Women’s and Children’s NHS Foundation Trust

Scott Hackett

University Hospitals Birmingham NHS Foundation Trust - Heartlands Hospital

Deepthi Jyothish

Birmingham Women’s and Children’s NHS Foundation Trust

Hari Krishnan Kanthimathinathan

Birmingham Women’s and Children’s NHS Foundation Trust - Paediatric Intensive Care Unit

Sean Monaghan

Birmingham Women’s and Children’s NHS Foundation Trust

Prasad Nagakumar

Birmingham Women’s and Children’s NHS Foundation Trust

Barnaby R. Scholefield

Birmingham Women’s and Children’s NHS Foundation Trust

Steven Welch

University Hospitals Birmingham NHS Foundation Trust - Heartlands Hospital

Naeem Khan

University of Birmingham - Clinical Immunology Service

Sian Faustini

University of Birmingham - Clinical Immunology Service

Kate Davies

Cardiff University - Systems Immunity Research Institute

Wioleta Zelek

Cardiff University - Systems Immunity Research Institute

Pamela Kearns

University of Birmingham - NIHR Birmingham Biomedical Research Centre and Institute of Cancer and Genomic Sciences

Graham Taylor

University of Birmingham - Institute of Immunology and Immunotherapy

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Multiple version iconThere are 2 versions of this paper

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; increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken when symptoms were resolving, identified recovery-associated immune features including CD163+ monocytes, emergence of a new population of immature neutrophils and, in some patients, a transient increase in arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL6 may be preferable to IL1 or TNF-a. We identified potential new 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.

Funding Information: Birmingham Women’s and Children’s Hospital Charity funded the single cell RNA sequencing analysis. No other external funding was received.

Declaration of Interests: None declared.

Ethics Approval Statement: Reviewed and approved by South of Birmingham Research Ethics Committee (REC: 17/WM/0453, IRAS: 233593).

Suggested Citation

Syrimi, Eleni and Fennell, Eanna and Richter, Alex G. and Vrljicak, Pavle and Stark, Richard and Ott, Sascha and Murray, Paul G. and Al-Abadi, Eslam and Chikermane, Ashish and Dawson, Pamela and Hackett, Scott and Jyothish, Deepthi and Krishnan Kanthimathinathan, Hari and Monaghan, Sean and Nagakumar, Prasad and Scholefield, Barnaby R. and Welch, Steven and Khan, Naeem and Faustini, Sian and Davies, Kate and Zelek, Wioleta and Kearns, Pamela and Taylor, Graham, The Innate and Adaptive Immune Landscape of SARS-CoV-2-Associated Multisystem Inflammatory Syndrome in Children (MIS-C) From Acute Disease to Recovery. Available at SSRN: https://ssrn.com/abstract=3889707 or http://dx.doi.org/10.2139/ssrn.3889707
This version of the paper has not been formally peer reviewed.

Eleni Syrimi

University of Birmingham - Institute of Immunology and Immunotherapy

Eanna Fennell

University of Limerick - Health Research Institute and the Bernal Institute

Castletroy, Co
Limerick
Ireland

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences ( email )

Edgbaston
Birminham, Birmingham B152TT
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

Birmingham
United Kingdom

Pavle Vrljicak

University of Warwick - Division of Biomedical Sciences

Richard Stark

University of Warwick - Bioinformatics Research Technology Platform ( email )

Gibbet Hill Rd.
Coventry, West Midlands CV4 8UW
United Kingdom

Sascha Ott

University of Warwick - Division of Biomedical Sciences

Paul G. Murray

University of Limerick - Health Research Institute and the Bernal Institute

Castletroy, Co
Limerick
Ireland

Eslam Al-Abadi

Birmingham Women’s and Children’s NHS Foundation Trust ( email )

Birmingham, B15 2TG
United Kingdom

Ashish Chikermane

Birmingham Women’s and Children’s NHS Foundation Trust ( email )

Birmingham, B15 2TG
United Kingdom

Pamela Dawson

Birmingham Women’s and Children’s NHS Foundation Trust ( email )

Birmingham, B15 2TG
United Kingdom

Scott Hackett

University Hospitals Birmingham NHS Foundation Trust - Heartlands Hospital ( email )

Mindelsohn Way
Edgbaston
Birmingham, B15 2TH
United Kingdom

Deepthi Jyothish

Birmingham Women’s and Children’s NHS Foundation Trust ( email )

Birmingham, B15 2TG
United Kingdom

Hari Krishnan Kanthimathinathan

Birmingham Women’s and Children’s NHS Foundation Trust - Paediatric Intensive Care Unit ( email )

Birmingham, B15 2TG
United Kingdom

Sean Monaghan

Birmingham Women’s and Children’s NHS Foundation Trust ( email )

Birmingham, B15 2TG
United Kingdom

Prasad Nagakumar

Birmingham Women’s and Children’s NHS Foundation Trust ( email )

Birmingham, B15 2TG
United Kingdom

Barnaby R. Scholefield

Birmingham Women’s and Children’s NHS Foundation Trust ( email )

Birmingham, B15 2TG
United Kingdom

Steven Welch

University Hospitals Birmingham NHS Foundation Trust - Heartlands Hospital ( email )

Mindelsohn Way
Edgbaston
Birmingham, B15 2TH
United Kingdom

Naeem Khan

University of Birmingham - Clinical Immunology Service

Edgbaston, B15 2TT
United Kingdom

Sian Faustini

University of Birmingham - Clinical Immunology Service ( email )

United Kingdom

Kate Davies

Cardiff University - Systems Immunity Research Institute

Aberconway Building
Colum Drive
Cardiff, CF10 3EU
United Kingdom

Wioleta Zelek

Cardiff University - Systems Immunity Research Institute ( email )

Cardiff, CF14 4XN
United Kingdom

Pamela Kearns

University of Birmingham - NIHR Birmingham Biomedical Research Centre and Institute of Cancer and Genomic Sciences ( email )

Birmingham
United Kingdom

Graham Taylor (Contact Author)

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Birmingham
United Kingdom

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