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

10.1016/j.ebiom.2022.104402

eBioMedicine

20th December 2022

Contributing to research themes:

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:

Affiliations:

a National Heart and Lung Institute, Imperial College London, UK

b NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, UK

c MRC-University of Glasgow Centre for Virus Research, Immunity and Inflammation, University of Glasgow, UK

d Cardiovascular Research Team, Imperial College Healthcare NHS Trust, London, UK

e Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK

f Centre for Medical Informatics, The Usher Institute, University of Edinburgh, Edinburgh, UK

g University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

h MRC Human Immunology Unit, University of Oxford, Oxford, UK

i Division of Infection, Immunity & Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

j Radcliffe Department of Medicine, University of Oxford, Oxford, UK

k Asthma and Lung UK, London, UK

l Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK

m Oxford Centre for Global Health Research, University of Oxford, Oxford, UK

n Institute for Lung Health, Leicester NIHR Biomedical Research Centre, University of Leicester, Leicester, UK

o Department of Population Health Sciences, University of Leicester, Leicester, UK

p Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK

q The Pandemic Institute, University of Liverpool, UK

Authors:

Felicity Liew,^a,* Shubha Talwar,^a Andy Cross,^b Brian J. Willett,^c Sam Scott,^c Nicola Logan,^c Matthew K. Siggins,^a Dawid Swieboda,^a Jasmin K. Sidhu,^a Claudia Efstathiou,^a Shona C. Moore,^b Chris Davis,^c Noura Mohamed,^d Jose Nunag,^d Clara King,^d A. A. Roger Thompson,^e Sarah L. Rowland-Jones,^e Annemarie B. Docherty,^fJames D. Chalmers,^g Ling-Pei Ho,^h Alexander Horsley,ⁱ Betty Raman,^j Krisnah Poinasamy,^k Michael Marks,^l Onn Min Kon,^a Luke Howard,^a Daniel G. Wootton,^b Susanna Dunachie,^m Jennifer K. Quint,^a Rachael A. Evans,ⁿ Louise V. Wain,^o Sara Fontanella,^a Thushan I. de Silva,^e Antonia Ho,^c Ewen Harrison,^f J. Kenneth Baillie,^p Malcolm G. Semple,^b,q Christopher Brightling,ⁿ Ryan S. Thwaites,^{a,r, ***} Lance Turtle,^{b,q,r, ****} and Peter J. M. Openshaw,^{a,r, **} on behalf of the ISARIC4C Investigators and the PHOSP-COVID collaborative group