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

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: 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.