Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses.

McNaughton, Anna L ORCID: 0000-0002-7436-8727, Paton, Robert S, Edmans, Matthew, Youngs, Jonathan ORCID: 0000-0001-8781-2615, Wellens, Judith ORCID: 0000-0002-1647-8151, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S ORCID: 0000-0002-6738-7823, Ball, Jonathan
et al (show 47 more authors) (2022) Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI insight, 7 (13). e156372-.

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The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

Item Type: Article
Uncontrolled Keywords: Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium, Scottish National Blood Transfusion Service (SNBTS) consortium, International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators, Humans, Antibodies, Viral, Epitopes, Antibody Formation, Spike Glycoprotein, Coronavirus, COVID-19, SARS-CoV-2
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 14 Jun 2022 15:59
Last Modified: 18 Jan 2023 21:00
DOI: 10.1172/jci.insight.156372
Open Access URL: https://insight.jci.org/articles/view/156372
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3156478