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Fatal COVID-19 Outcomes are Associated with an Antibody Response Targeting Epitopes Shared with Endemic Coronaviruses

32 Pages Posted: 2 Jun 2021 Publication Status: Review Complete

See all articles by Anna L. McNaughton

Anna L. McNaughton

University of Oxford

Robert S. Paton

University of Oxford

Matthew Edmans

University of Oxford

Jonathan Youngs

St. George’s University of London - Institute of Infection & Immunity

Judith Wellens

University of Oxford

Prabhjeet Phalora

University of Oxford

Alex Fyfe

University of Oxford - Peter Medawar Building for Pathogen Research

Sandra Belij-Rammerstorfer

University of Oxford - The Jenner Institute

Jai S. Bolton

University of Oxford

Jonathan Ball

St. George's University - Intensive Care Medicine

George Carnell

University of Cambridge

Wanwisa Dejnirattisai

University of Oxford - Wellcome Centre for Human Genetics

Christina Dold

University of Oxford - Oxford Vaccine Group

David W. Eyre

University of Oxford

Philip Hopkins

Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College, London

Alison Howarth

University of Oxford

Kreepa Kooblall

University of Oxford

Hannah Klim

University of Oxford

Susannah Leaver

St. George's University - General Intensive Care

Lian Lee

University of Oxford

Cesar Lopez-Camacho

University of Oxford - Wellcome Centre for Human Genetics

Sheila Lumley

University of Oxford - Nuffield Department of Medicine

Derek Macallan

St George's, University of London

Alexander J. Mentzer

University of Oxford - Wellcome Centre for Human Genetics; University of Oxford - Li Ka Shing Centre for Health Information and Discovery

Nicholas Provine

University of Oxford

Jeremy Ratcliff

University of Oxford

Jose Slon-Campos

University of Oxford - Wellcome Centre for Human Genetics

Donal Skelly

University of Oxford - Nuffield Department of Clinical Neurosciences; Oxford University Hospitals NHS Foundation Trust

Lucas Stolle

University of Oxford

Piyada Supasa

University of Oxford - Wellcome Centre for Human Genetics

Nigel Temperton

University of Kent - Viral Pseudotype Unit

Chris Walker

Meso-­‐Scale Diagnostics

Beibei Wang

University of Oxford - Wellcome Centre for Human Genetics

Duncan Wyncoll

Guy's and St Thomas' NHS Foundation Trust - Intensive Care Medicine

OPTIC consortium

Independent

SNBTS consortium

Independent

Peter Simmonds

University of Oxford - Nuffield Department of Medicine

Teresa Lambe

University of Oxford - The Jenner Institute

J. Kenneth Baillie

University of Edinburgh - Roslin Institute

Malcolm Semple

University of Liverpool - Health Protection Research Unit in Emerging and Zoonotic Infections

Peter Openshaw

Imperial College London - National Heart and Lung Institute (NHLI)

ISARIC4C Investigators

Independent

Uri Obolski

Tel Aviv University

Marc Turner

Leidos Inc.

Miles W. Carroll

University of Oxford - Wellcome Centre for Human Genetics

Juthathip Mongkolspaya

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Gavin R. Screaton

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI)

Stephen H. Kennedy

University of Oxford

Lisa Jarvis

affiliation not provided to SSRN

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research

José Lourenço

University of Oxford - Department of Zoology

Philippa Matthews

University of Oxford - Peter Medawar Building for Pathogen Research

Tihana Bicanic

St. George’s University of London - Institute of Infection & Immunity

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research

Sunetra Gupta

University of Oxford - Department of Zoology

Craig P. Thompson

University of Oxford - Peter Medawar Building for Pathogen Research

More...

Abstract

It is unclear whether prior endemic coronavirus infections affect COVID-19 severity. Here, we show that in cases of fatal COVID-19, antibody responses to the SARS-COV-2 spike are directed against epitopes shared with endemic beta-coronaviruses in the S2 subunit of the SARS-CoV-2 spike protein. This immune response is associated with the compromised production of a de novo SARS-CoV-2 spike response among individuals with fatal COVID-19 outcomes.

Funding: This work was supported by the Georg and Emily von Opel Foundation, the National Institute for Health Research (NIHR) [award CO-­‐CIN-­‐01], the Medical Research Council [grant MC_PC_19059], ME was supported by The Leona M. and Harry B. Helmsley Charitable Trust on May 31, 2021 for the project titled, "ICARUS –IBD: International study of COVID-­‐19 Antibody Response Under Sustained immune suppression in Inflammatory Bowel Disease. RP also supported by funds provided under Professor RW Snow’s Wellcome Trust Principal Fellowship (# 212176). Meso Scale Diagnostics (USA) provided loan of equipment, reagents and technical support. JSB was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB/M011224/1]. CPT was funded by an ERC research grant UNIFLUVAC’ and two MRC CiC grants (Ref: BR00140). ALM is funded by a NIHR Research Capability Funding grant. HJK is supported by The Future of Humanity Institute at the University of Oxford DPhil Scholarship program. DE is funded by the Robertson Foundation. The funders played no role in the design, execution or reporting of the study.

Declaration of Interest: DE declares lecture fees from Gilead. CPT and SG hold funding from Blue Water Vaccines. All others have nothing to disclose.

Ethical Approval: Ethical approval was obtained for the Scottish National Blood Transfusion Service (SNBTS) anonymous archive -­‐ IRAS project number 18005. SNBTS blood donors gave fully informed consent to virological testing, donation was made under the SNBTS Blood Establishment Authorisation and the study was approved by the SNBTS Research and Sample Governance Committee.

Suggested Citation

McNaughton, Anna L. and Paton, Robert S. and Edmans, Matthew and Youngs, Jonathan and Wellens, Judith and Phalora, Prabhjeet and Fyfe, Alex and Belij-Rammerstorfer, Sandra and Bolton, Jai S. and Ball, Jonathan and Carnell, George and Dejnirattisai, Wanwisa and Dold, Christina and Eyre, David W. and Hopkins, Philip and Howarth, Alison and Kooblall, Kreepa and Klim, Hannah and Leaver, Susannah and Lee, Lian and Lopez-Camacho, Cesar and Lumley, Sheila and Macallan, Derek and Mentzer, Alexander J. and Provine, Nicholas and Ratcliff, Jeremy and Slon-Campos, Jose and Skelly, Donal and Skelly, Donal and Stolle, Lucas and Supasa, Piyada and Temperton, Nigel and Walker, Chris and Wang, Beibei and Wyncoll, Duncan and consortium, OPTIC and consortium, SNBTS and Simmonds, Peter and Lambe, Teresa and Baillie, J. Kenneth and Semple, Malcolm and Openshaw, Peter and Investigators, ISARIC4C and Obolski, Uri and Turner, Marc and Carroll, Miles W. and Mongkolspaya, Juthathip and Screaton, Gavin R. and Kennedy, Stephen H. and Jarvis, Lisa and Barnes, Eleanor and Dunachie, Susanna and Lourenço, José and Matthews, Philippa and Bicanic, Tihana and Klenerman, Paul and Gupta, Sunetra and Thompson, Craig P., Fatal COVID-19 Outcomes are Associated with an Antibody Response Targeting Epitopes Shared with Endemic Coronaviruses. Available at SSRN: https://ssrn.com/abstract=3858917 or http://dx.doi.org/10.2139/ssrn.3858917
This version of the paper has not been formally peer reviewed.

Anna L. McNaughton

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Robert S. Paton

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Matthew Edmans

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Jonathan Youngs

St. George’s University of London - Institute of Infection & Immunity ( email )

London
United Kingdom

Judith Wellens

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Prabhjeet Phalora

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Alex Fyfe

University of Oxford - Peter Medawar Building for Pathogen Research

South Parks Road
OX2 3SY
United Kingdom

Sandra Belij-Rammerstorfer

University of Oxford - The Jenner Institute ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Jai S. Bolton

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Jonathan Ball

St. George's University - Intensive Care Medicine

West Indies
Grenada

George Carnell

University of Cambridge

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Wanwisa Dejnirattisai

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Christina Dold

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

David W. Eyre

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Philip Hopkins

Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College, London

Alison Howarth

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Kreepa Kooblall

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Hannah Klim

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Susannah Leaver

St. George's University - General Intensive Care ( email )

West Indies
Grenada

Lian Lee

University of Oxford

Cesar Lopez-Camacho

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Sheila Lumley

University of Oxford - Nuffield Department of Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Derek Macallan

St George's, University of London ( email )

Cranmer Terrace
London, SW17 0RE
United Kingdom
+442087250283 (Phone)

HOME PAGE: http://https://www.sgul.ac.uk/profiles/derek-macallan

Alexander J. Mentzer

University of Oxford - Wellcome Centre for Human Genetics ( email )

University of Oxford - Li Ka Shing Centre for Health Information and Discovery ( email )

Oxford, OX3 7FZ
United Kingdom

Nicholas Provine

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Jeremy Ratcliff

University of Oxford

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Jose Slon-Campos

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Donal Skelly

Oxford University Hospitals NHS Foundation Trust ( email )

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

University of Oxford - Nuffield Department of Clinical Neurosciences ( email )

Oxford
United Kingdom

Lucas Stolle

University of Oxford

Piyada Supasa

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Nigel Temperton

University of Kent - Viral Pseudotype Unit ( email )

Chris Walker

Meso-­‐Scale Diagnostics

MD
United States

Beibei Wang

University of Oxford - Wellcome Centre for Human Genetics

Oxford, OX3 7BN
United Kingdom

Duncan Wyncoll

Guy's and St Thomas' NHS Foundation Trust - Intensive Care Medicine ( email )

London
United Kingdom

OPTIC Consortium

Independent

SNBTS Consortium

Independent

Peter Simmonds

University of Oxford - Nuffield Department of Medicine ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

Teresa Lambe

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

J. Kenneth Baillie

University of Edinburgh - Roslin Institute ( email )

United Kingdom

HOME PAGE: http://baillielab.net

Malcolm Semple

University of Liverpool - Health Protection Research Unit in Emerging and Zoonotic Infections ( email )

Liverpool
United Kingdom

Peter Openshaw

Imperial College London - National Heart and Lung Institute (NHLI) ( email )

Uri Obolski

Tel Aviv University

Tel-Aviv
Israel

Marc Turner

Leidos Inc.

United States

Miles W. Carroll

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Juthathip Mongkolspaya

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI) ( email )

Gavin R. Screaton

University of Oxford - Chinese Academy of Medical Science Oxford Institute (COI) ( email )

Stephen H. Kennedy

University of Oxford

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Lisa Jarvis

affiliation not provided to SSRN

Eleanor Barnes

Oxford University Hospitals NHS Foundation Trust

Headley Way
Headington
Oxford, OX3 9DU
United Kingdom

Susanna Dunachie

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

José Lourenço

University of Oxford - Department of Zoology ( email )

New Radcliffe House
Radcliffe Observatory Quarter
Oxford, OX13 5QL
United Kingdom

Philippa Matthews

University of Oxford - Peter Medawar Building for Pathogen Research

Tihana Bicanic

St. George’s University of London - Institute of Infection & Immunity ( email )

London
United Kingdom

Paul Klenerman

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

Sunetra Gupta

University of Oxford - Department of Zoology ( email )

New Radcliffe House
Radcliffe Observatory Quarter
Oxford, OX13 5QL
United Kingdom

Craig P. Thompson (Contact Author)

University of Oxford - Peter Medawar Building for Pathogen Research ( email )

South Parks Road
OX2 3SY
United Kingdom

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