SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

Background

Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced.

Methods

In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data.

Findings

Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.

Interpretation

The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity.

Author list

Authors:

Felicity Liew,1* Shubha Talwar,1 Andy Cross,2 Brian J. Willett,3 Sam Scott,3 Nicola Logan,3 Matthew K. Siggins,1 Dawid Swieboda,1 Jasmin K. Sidhu,1 Claudia Efstathiou,1 Shona C. Moore,2 Chris Davis,3 Noura Mohamed,4 Jose Nunag,4 Clara King,4 A. A. Roger Thompson,5 Sarah L. Rowland-Jones,5 Annemarie B. Docherty,6 James D. Chalmers,7 Ling-Pei Ho,8 Alexander Horsley,9 Betty Raman,10 Krisnah Poinasamy,11 Michael Marks,12 Onn Min Kon,1 Luke Howard,1 Daniel G. Wootton,3 Susanna Dunachie,13 Jennifer K. Quint,a Rachael A. Evans,14 Louise V. Wain,15 Sara Fontanella,1 Thushan I. de Silva,5 Antonia Ho,3 Ewen Harrison,6 J. Kenneth Baillie,16 Malcolm G. Semple,2,17 Christopher Brightling,14 Ryan S. Thwaites,1,18*** Lance Turtle,2,16,17,18**** and Peter J. M. Openshaw,1,18** on behalf of the ISARIC4C Investigators and the PHOSP-COVID collaborative group

Affiliations:

  1. National Heart and Lung Institute, Imperial College London, UK
  2. NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK
  3. MRC-University of Glasgow Centre for Virus Research, Immunity and Inflammation, University of Glasgow, UK
  4. Cardiovascular Research Team, Imperial College Healthcare NHS Trust, London, UK
  5. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK
  6. Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK
  7. University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
  8. MRC Human Immunology Unit, University of Oxford, Oxford, UK
  9. Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK 
  10. Radcliffe Department of Medicine, University of Oxford, Oxford, UK
  11. Asthma and Lung UK, London, UK
  12. Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK
  13. Oxford Centre for Global Health Research, University of Oxford, Oxford, UK
  14. Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester, UK
  15. Department of Population Health Sciences, University of Leicester, Leicester, UK
  16. Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
  17. The Pandemic Institute, University of Liverpool, UK
Novel Coronavirus SARS-CoV-2

10.1016/j.ebiom.2022.104402

eBioMedicine

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