SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination.
Creators: name: Liew, Felicity
name: Talwar, Shubha
name: Cross, Andy
name: Willett, Brian J
name: Scott, Sam
name: Logan, Nicola
name: Siggins, Matthew K
name: Swieboda, Dawid
name: Sidhu, Jasmin K
name: Efstathiou, Claudia
name: Moore, Shona C
name: Davis, Chris
name: Mohamed, Noura
name: Nunag, Jose
name: King, Clara
name: Thompson, AA Roger
name: Rowland-Jones, Sarah L
name: Docherty, Annemarie B
name: Chalmers, James D
name: Ho, Ling-Pei
name: Horsley, Alexander
name: Raman, Betty
name: Poinasamy, Krisnah
name: Marks, Michael
name: Kon, Onn Min
name: Howard, Luke
name: Wootton, Daniel G
name: Dunachie, Susanna
name: Quint, Jennifer K
name: Evans, Rachael A
name: Wain, Louise V
name: Fontanella, Sara
name: de Silva, Thushan I
name: Ho, Antonia
name: Harrison, Ewen
name: Baillie, J Kenneth
name: Semple, Malcolm G
name: Brightling, Christopher
name: Thwaites, Ryan S
name: Turtle, Lance
name: Openshaw, Peter JM
name: Investigators, ISARIC4C
name: group, PHOSP-COVID collaborative
Publisher: name: The Francis Crick Institute
Year: 2023
Subjects: classificationCode: Chemical Biology & High Throughput
subject: Chemical Biology &amp; High Throughput
classificationCode: Computational & Systems Biology
subject: Computational &amp; Systems Biology
classificationCode: Ecology,Evolution & Ethology
subject: Ecology,Evolution &amp; Ethology
classificationCode: Metabolism
subject: Metabolism
classificationCode: Structural Biology & Biophysics
subject: Structural Biology &amp; Biophysics

description: 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 &lt; 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p &lt; 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p &lt; 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.