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Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
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(2022) Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight, 7 (13). e156372. doi:10.1172/jci.insight.156372 ISSN 2379-3708.
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Official URL: http://dx.doi.org/10.1172/jci.insight.156372
Abstract
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: | Journal Article | |||||||||||||||||||||||||||||||||
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| Subjects: | Q Science > QR Microbiology > QR355 Virology | |||||||||||||||||||||||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||||||||||||||||||||||||||
| Library of Congress Subject Headings (LCSH): | Coronaviruses, COVID-19 (Disease) , COVID-19 (Disease) -- Immunodiagnosis | |||||||||||||||||||||||||||||||||
| Journal or Publication Title: | JCI Insight | |||||||||||||||||||||||||||||||||
| Publisher: | American Society for Clinical Investigation | |||||||||||||||||||||||||||||||||
| ISSN: | 2379-3708 | |||||||||||||||||||||||||||||||||
| Official Date: | 8 July 2022 | |||||||||||||||||||||||||||||||||
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| Volume: | 7 | |||||||||||||||||||||||||||||||||
| Number: | 13 | |||||||||||||||||||||||||||||||||
| Article Number: | e156372 | |||||||||||||||||||||||||||||||||
| DOI: | 10.1172/jci.insight.156372 | |||||||||||||||||||||||||||||||||
| Status: | Peer Reviewed | |||||||||||||||||||||||||||||||||
| Publication Status: | Published | |||||||||||||||||||||||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||||||||||||||||||||||||||
| Copyright Holders: | © 2022, McNaughton et al. | |||||||||||||||||||||||||||||||||
| Date of first compliant deposit: | 29 July 2022 | |||||||||||||||||||||||||||||||||
| Date of first compliant Open Access: | 29 July 2022 | |||||||||||||||||||||||||||||||||
| RIOXX Funder/Project Grant: |
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