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07 08, 2022;7 (13):

Fatal COVID-19 outcomes are associated with an 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 S Bolton, Jonathan Ball, George W Carnell, Wanwisa Dejnirattisai, Christina Dold, David W Eyre, Philip Hopkins, Alison Howarth, Kreepa Kooblall, Hannah Klim, Susannah Leaver, Lian Ni Lee, César López-Camacho, Sheila F Lumley, Derek C Macallan, Alexander J Mentzer, Nicholas M Provine, Jeremy Ratcliff, Jose Slon-Compos, Donal Skelly, Lucas Stolle, Piyada Supasa, Nigel Temperton, Chris Walker, Beibei Wang, Duncan Wyncoll, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium, Scottish National Blood Transfusion Service (SNBTS) consortium, Peter Simmonds, Teresa Lambe, John Kenneth Baillie, Malcolm G Semple, Peter Jm Openshaw, International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators, Uri Obolski, Marc Turner, Miles Carroll, Juthathip Mongkolsapaya, Gavin Screaton, Stephen H Kennedy, Lisa Jarvis, Eleanor Barnes, Susanna Dunachie, José Lourenço, Philippa C Matthews, Tihana Bicanic, Paul Klenerman, Sunetra Gupta, Craig P Thompson
Author Information
  1. Anna L McNaughton: Peter Medawar Building for Pathogen Research.
  2. Robert S Paton: Peter Medawar Building for Pathogen Research.
  3. Matthew Edmans: Peter Medawar Building for Pathogen Research.
  4. Jonathan Youngs: Institute of Infection & Immunity, St George's University of London, London, United Kingdom.
  5. Judith Wellens: Peter Medawar Building for Pathogen Research.
  6. Prabhjeet Phalora: Peter Medawar Building for Pathogen Research.
  7. Alex Fyfe: Peter Medawar Building for Pathogen Research.
  8. Sandra Belij-Rammerstorfer: The Jenner Institute Laboratories, University of Oxford, Oxford, United Kingdom.
  9. Jai S Bolton: Peter Medawar Building for Pathogen Research.
  10. Jonathan Ball: General Intensive Care service, St George's University Hospital National Health Service (NHS) Trust, London, United Kingdom.
  11. George W Carnell: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
  12. Wanwisa Dejnirattisai: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  13. Christina Dold: Oxford Vaccine Group, Department of Paediatrics, and.
  14. David W Eyre: Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
  15. Philip Hopkins: Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College, London, United Kingdom.
  16. Alison Howarth: Department of Microbiology/Infectious Diseases, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom.
  17. Kreepa Kooblall: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, and.
  18. Hannah Klim: Peter Medawar Building for Pathogen Research.
  19. Susannah Leaver: General Intensive Care service, St George's University Hospital National Health Service (NHS) Trust, London, United Kingdom.
  20. Lian Ni Lee: Peter Medawar Building for Pathogen Research.
  21. César López-Camacho: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  22. Sheila F Lumley: Peter Medawar Building for Pathogen Research.
  23. Derek C Macallan: Institute of Infection & Immunity, St George's University of London, London, United Kingdom.
  24. Alexander J Mentzer: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  25. Nicholas M Provine: Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
  26. Jeremy Ratcliff: Peter Medawar Building for Pathogen Research.
  27. Jose Slon-Compos: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  28. Donal Skelly: Peter Medawar Building for Pathogen Research.
  29. Lucas Stolle: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
  30. Piyada Supasa: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  31. Nigel Temperton: Viral Pseudotype Unit, Medway School of Pharmacy, University of Kent, Chatham, United Kingdom.
  32. Chris Walker: Meso Scale Diagnostics, Rockville, Maryland, USA.
  33. Beibei Wang: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  34. Duncan Wyncoll: Intensive Care Medicine, Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom.
  35. Peter Simmonds: Peter Medawar Building for Pathogen Research.
  36. Teresa Lambe: The Jenner Institute Laboratories, University of Oxford, Oxford, United Kingdom.
  37. John Kenneth Baillie: Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
  38. Malcolm G Semple: NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.
  39. Peter Jm Openshaw: National Heart and Lung Institute, Imperial College, London, United Kingdom.
  40. Uri Obolski: School of Public Health, Faculty of Medicine, and.
  41. Marc Turner: National Microbiology Reference Unit, Scottish National Blood Transfusion Service, Edinburgh, United Kingdom.
  42. Miles Carroll: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  43. Juthathip Mongkolsapaya: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  44. Gavin Screaton: Wellcome Centre for Human Genetics, Nuffield Department of Medicine.
  45. Stephen H Kennedy: Nuffield Department of Women's & Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
  46. Lisa Jarvis: National Microbiology Reference Unit, Scottish National Blood Transfusion Service, Edinburgh, United Kingdom.
  47. Eleanor Barnes: Peter Medawar Building for Pathogen Research.
  48. Susanna Dunachie: Peter Medawar Building for Pathogen Research.
  49. José Lourenço: Peter Medawar Building for Pathogen Research.
  50. Philippa C Matthews: Peter Medawar Building for Pathogen Research.
  51. Tihana Bicanic: Institute of Infection & Immunity, St George's University of London, London, United Kingdom.
  52. Paul Klenerman: Peter Medawar Building for Pathogen Research.
  53. Sunetra Gupta: Peter Medawar Building for Pathogen Research.
  54. Craig P Thompson: Peter Medawar Building for Pathogen Research.
PMID: 35608920 DOI: 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.

Keywords

Adaptive immunity Immunology Imprinting Infectious disease

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Grants

  1. BB/M011224/1/Biotechnology and Biological Sciences Research Council
  2. MC_PC_19025/Medical Research Council
  3. MC_PC_19059/Medical Research Council

MeSH Term

Antibodies, Viral
Antibody Formation
COVID-19
Epitopes
Humans
SARS-CoV-2
Spike Glycoprotein, Coronavirus

Chemicals

Antibodies, Viral
Epitopes
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 263

Word Cloud

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