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

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish
Article numbere156372
JournalJCI insight
Issue number13
StatePublished - 8 Jul 2022


FundersFunder number
Leona M. and Harry B. Helmsley Charitable Trust
Wellcome Trust212176
Wellcome Trust
Robertson Foundation222426/Z/21/Z
Robertson Foundation
Manchester Biomedical Research Centre
Medical Research CouncilMC_PC_19059
Medical Research Council
Biotechnology and Biological Sciences Research CouncilBB/M011224/1
Biotechnology and Biological Sciences Research Council
National Institute for Health and Care ResearchCO-CIN-01
National Institute for Health and Care Research
European Research Council


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