Nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination



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This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.


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.


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.


Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months. Nasal and plasma anti-S IgG remained elevated for at least 12 months with high plasma neutralising titres against all variants. Of 180 with complete data, 160 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. Samples 12 months after admission showed no association between nasal IgA and plasma IgG responses, indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination.


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:


  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. Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK
  5. Cardiovascular Research Team, Imperial College Healthcare NHS Trust, London, UK.
  6. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, 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. Centre for inflammation research, University of Edinburgh, Edinburgh, UK.
  16. Department of Health Sciences, University of Leicester, Leicester, UK.
  17. The Pandemic Institute, University of Liverpool.


Felicity Liew1 (MRCP), Shubha Talwar1 (MRes), Andy Cross2 (PhD), Brian J. Willett3 (PhD), Sam Scott3 (MSc), Nicola Logan3 (MSc), Matthew K. Siggins1 (PhD), Dawid Swieboda1 (PhD), Jasmin K. Sidhu1 (PhD), Claudia Efstathiou1(MSc), Shona C. Moore2 (PhD), Chris Davis3 (PhD), Noura Mohamed5 (MSc), Jose Nunag5 (MSc), Clara King5 (BSc), A. A. Roger Thompson6 (MRCP), Sarah L. Rowland-Jones6 (FMedSci), Annemarie B. Docherty4 (FRCA), James D. Chalmers7 (FRCPE), Ling- Pei Ho8 (FRCP), Alexander Horsley9 (PhD), Betty Raman10 (FRACP), Krisnah Poinasamy11(LLM), Michael Marks12 (PhD), Onn Min Kon1 (MD), Luke Howard(FRCP), Daniel G. Wootton2 (MRCP), Susanna Dunachie13 (FRCP), Jennifer K. Quint(FRCP), Rachael A. Evans14 (FRCP) , Louise V . Wain14 (PhD), Sara Fontanella(PhD), Thushan I. de Silva(PhD), Antonia Ho3 (PhD), Ewen Harrison(FRCS), J. Kenneth Baillie15 (FMedSci), Malcolm G. Semple2,17 (FRCPE), Christopher Brightling14 (FMedSci), Ryan S. Thwaites1*† (PhD), Lance Turtle2,17*† (MRCP), Peter J.M. Openshaw1*† (FMedSci) and on behalf of the ISARIC4C Investigators and the PHOSP-COVID collaborative group.