Fatal COVID-19 outcomes tied to antibody response targeting epitopes shared with endemic coronaviruses

 Anna L McNaughton, Robert S Paton, Matthew Edmans, Jonathan Youngs, Judith Wellens, Prabhjeet Phalora, Alex Fyfe, Sandra Belij-Rammerstorfer, Jai Bolton, Jonathan Ball, George Carnell, Wanwisa Dejnirattisai, Christina Dold, David W Eyre, Philip Hopkins, Alison Howarth, Kreepa Kooblall, Hannah Klim, Susannah Leaver, Lian Lee, Cesar Lopez-Camacho, Sheila F Lumley, Derek Macallan, Alexander J Mentzer, Nicholas Provine, Jeremy Ratcliff, Jose Slon-Compos, Donal Skelly, Lucas Stolle, Piyada Supasa, Nigel Temperton, Chris Walker, Beibei Wang, Duncan Wyncoll, OPTIC consortium, SNBTS consortium, Peter Simmonds, Teresa Lambe, Kenneth Baillie, Malcolm G Semple, Peter IM Openshaw, ISARIC4C consortium, Uri Obolski, Marc Turner, Miles Carroll, Juthathip Mongkolsapaya, Gavin Screaton, Stephen H Kennedy, Lisa Jarvis, Eleanor Barnes, Susanna Dunachie, Jose Lourenco, Philippa C Matthews, Tihana Bicanic, Paul Klenerman, Sunetra Gupta, Craig Peter Thompson

doi: https://doi.org/10.1101/2021.05.04.21256571

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.05.04.21256571v1.full.pdf

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.

Competing Interest Statement

DE declares lecture fees from Gilead. CPT and SG hold funding from Blue Water Vaccines.

Funding Statement

This work was supported by the Georg and Emily von Opel Foundation, the National Institute for Health Research (NIHR) [award COCIN01], the Medical Research Council [grant MCPC19059], 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 Snows 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 BBM0112241]. 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.

https://www.medrxiv.org/content/10.1101/2021.05.04.21256571v1