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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 ORCID:, Capitani, Lorenzo, Burnell, Stephanie, Rees, Tara, Smart, Kathryn, Somerville, Michelle, Gallimore, Awen ORCID:, Perera, Marianne, Potts, Martin, Metaxaki, Marina, Krishna, Benjamin, Jackson, Hannah, Tighe, Paddy, Onion, David, Godkin, Andrew ORCID:, Wills, Mark and Fairclough, Lucy 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) , 147. 10.1007/s10875-024-01739-0

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:, Type: open-access
Publisher: Springer
ISSN: 0271-9142
Date of First Compliant Deposit: 11 June 2024
Date of Acceptance: 20 May 2024
Last Modified: 11 Jun 2024 09:15

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