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

Liew, F. et al. (2023) SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination. EBioMedicine, 87, 104402. (doi: 10.1016/j.ebiom.2022.104402) (PMID:36543718) (PMCID:PMC9762734)

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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. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Scott, Mr Sam and Davis, Dr Chris and Logan, Miss Nicola and Willett, Professor Brian and Ho, Dr Antonia
Authors: Liew, F., Talwar, S., Cross, A., Willett, B. J., Scott, S., Logan, N., Siggins, M. K., Swieboda, D., Sidhu, J. K., Efstathiou, C., Moore, S. C., Davis, C., Mohamed, N., Nunag, J., King, C., Thompson, A. A. R., Rowland-Jones, S. L., Docherty, A. B., Chalmers, J. D., Ho, L.-P., Horsley, A., Raman, B., Poinasamy, K., Marks, M., Kon, O. M., Howard, L., Wootton, D. G., Dunachie, S., Quint, J. K., Evans, R. A., Wain, L. V., Fontanella, S., de Silva, T. I., Ho, A., Harrison, E., Baillie, J. K., Semple, M. G., Brightling, C., Thwaites, R. S., Turtle, L., and Openshaw, P. J.M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:EBioMedicine
ISSN (Online):2352-3964
Published Online:19 December 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in EBioMedicine 87: 104402
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630014Cross-Cutting Programme – Viral Genomics and Bioinformatics (Programme 9)David RobertsonMedical Research Council (MRC)MC_UU_12014/12III - Centre for Virus Research