Lower Humoral and Cellular Immunity Following Asymptomatic SARS-CoV-2 Infection Compared to Symptomatic Infection in Education (The ACE Cohort)

Hopkins, Georgina; Gomez, Nancy; Tucis, Davis; Bartlett, Laura; Steers, Graham; Burns, Ellie; Brown, Michaela; Harvey-Cowlishaw, Tyler; Santos, Rute; Lauder, Sarah N; Scurr, Martin; Capitani, Lorenzo; Burnell, Stephanie; Rees, Tara; Smart, Kathryn; Somerville, Michelle; Gallimore, Awen; Perera, Marianne; Potts, Martin; Metaxaki, Marina; Krishna, Benjamin; Jackson, Hannah; Tighe, Paddy; Onion, David; Godkin, Andrew; Wills, Mark; Fairclough, Lucy

Abstract

Purpose
Asymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a longitudinal cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort).

Methods
Asymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. 51 participant’s anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron B.1.1.529.1.

Results
Asymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4+ CD45RA+ T cells and activated CD8+ T cells than symptomatic participants, though these differences dissipated after vaccination.

Conclusions
Asymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants.

Citation

Hopkins, G., Gomez, N., Tucis, D., Bartlett, L., Steers, G., Burns, E., Brown, M., Harvey-Cowlishaw, T., Santos, R., Lauder, S. N., Scurr, M., Capitani, L., Burnell, S., Rees, T., Smart, K., Somerville, M., Gallimore, A., Perera, M., Potts, M., Metaxaki, M., …Fairclough, L. (2024). Lower Humoral and Cellular Immunity Following Asymptomatic SARS-CoV-2 Infection Compared to Symptomatic Infection in Education (The ACE Cohort). Journal of Clinical Immunology, 44(6), Article 147. https://doi.org/10.1007/s10875-024-01739-0

• Journal Article Type: Article
• Acceptance Date: May 20, 2024
• Online Publication Date: Jun 10, 2024
• Publication Date: 2024-08
• Deposit Date: Aug 6, 2024
• Publicly Available Date: Aug 20, 2024
• Journal: Journal of Clinical Immunology
• Print ISSN: 0271-9142
• Electronic ISSN: 1573-2592
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 44
• Issue: 6
• Article Number: 147
• DOI: https://doi.org/10.1007/s10875-024-01739-0
• Keywords: Asymptomatic, Symptomatic, Antibody, SARS-CoV-2, T cells, Vaccination
• Public URL: https://nottingham-repository.worktribe.com/output/36280445
• Publisher URL: https://link.springer.com/article/10.1007/s10875-024-01739-0