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.
| Original language | English |
|---|---|
| Article number | e156372 |
| Number of pages | 17 |
| Journal | JCI Insight |
| Volume | 7 |
| Issue number | 13 |
| Early online date | 24 May 2022 |
| DOIs | |
| Publication status | Published - 8 Jul 2022 |
Bibliographical note
Acknowledgments:We would like to express our gratitude and acknowledge the contribution of the staff at Oxford University Hospitals NHS Foundation Trust, SNBTS, and St George’s University Hospitals NHS Foundation Trust (London) who were involved in the provision and preparation of samples analyzed in this project. We acknowledge the wider support of the ISARIC4C, OPTIC, and SNBTS research consortia. This work was supported by the Medical Research Council (MRC; 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 “International study of COVID-19 Antibody Response Under Sustained immune suppression in IBD.” RP was supported by funds provided under Professor RW Snow’s Wellcome Trust Principal Fellowship (number 212176). MSD (USA) provided loan of equipment, reagents, and technical support. JSB was supported by funding from the Biotechnology and Biological Sciences Research Council (grant number BB/M011224/1). CPT was funded by an European Research Council research grant, UNIFLUVAC, and by 2 MRC Confidence in Concept grants (Ref: BR00140). ALM is funded by a National Institute for Health Research (NIHR) Research Capability Funding grant (CO-CIN-01). ALM, RP, and SG were supported by the Georg and Emily von Opel Foundation. HK is supported by Future of Humanity Institute at the University of Oxford DPhil Scholarship program. DWE is funded by the Robertson Foundation. PK was funded by a Wellcome Trust grant (ref. 222426/Z/21/Z). EB is supported by the Oxford NIHR Biomedical Research Centre and is an NIHR Senior Investigator. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The funders played no role in the design, execution, or reporting of the study.