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

10.1101/2022.09.09.22279759

MedRxiv

9th September 2022

Contributing to research themes:

This research has not been peer-reviewed.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.

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

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. 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.

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:

Affiliations:

National Heart and Lung Institute, Imperial College London, UK.
NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK.
MRC-University of Glasgow Centre for Virus Research, Immunity and Inflammation, University of Glasgow, UK.
Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK
Cardiovascular Research Team, Imperial College Healthcare NHS Trust, London, UK.
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
MRC Human Immunology Unit, University of Oxford, Oxford, UK.
Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Asthma and Lung UK, London, UK.
Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK.
Oxford Centre for Global Health Research, University of Oxford, Oxford UK.
Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester, UK.
Centre for inflammation research, University of Edinburgh, Edinburgh, UK.
Department of Health Sciences, University of Leicester, Leicester, UK.
The Pandemic Institute, University of Liverpool.

Authors:

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 Howard¹(FRCP), Daniel G. Wootton² (MRCP), Susanna Dunachie¹³ (FRCP), Jennifer K. Quint¹(FRCP), Rachael A. Evans¹⁴(FRCP) , Louise V . Wain¹⁴(PhD), Sara Fontanella¹(PhD), Thushan I. de Silva⁶(PhD), Antonia Ho³ (PhD), Ewen Harrison⁴(FRCS), J. Kenneth Baillie¹⁵ (FMedSci), Malcolm G. Semple^2,17 (FRCPE), Christopher Brightling¹⁴(FMedSci), Ryan S. Thwaites¹*† (PhD), Lance Turtle^2,17*† (MRCP), Peter J.M. Openshaw¹*† (FMedSci) and on behalf of the ISARIC4C Investigators and the PHOSP-COVID collaborative group.