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Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members

Jay, Cecilia, Adland, Emily, Csala, Anna, Dold, Christina, Edmans, Matthew, Hackstein, Carl-Philipp, Jamsen, Anni, Lim, Nicholas, Longet, Stephanie, Ogbe, Ane, Sampson, Oliver, Skelly, Donal, Spiller, Owen B. ORCID:, Stafford, Lizzie, Thompson, Craig P., Turtle, Lance, Barnes, Ellie, Dunachie, Susanna, Carroll, Miles, Klenerman, Paul, Conlon, Chris, Goulder, Philip and Jones, Lucy C. 2023. Cellular immunity to SARS-CoV-2 following intrafamilial exposure in seronegative family members. Frontiers in Immunology 14 , 1248658. 10.3389/fimmu.2023.1248658

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Introduction: Family studies of antiviral immunity provide an opportunity to assess virus-specific immunity in infected and highly exposed individuals, as well as to examine the dynamics of viral infection within families. Transmission of SARS-CoV-2 between family members represented a major route for viral spread during the early stages of the pandemic, due to the nature of SARS-CoV-2 transmission through close contacts. Methods: Here, humoral and cellular immunity is explored in 264 SARS-CoV-2 infected, exposed or unexposed individuals from 81 families in the United Kingdom sampled in the winter of 2020 before widespread vaccination and infection. Results: We describe robust cellular and humoral immunity into COVID-19 convalescence, albeit with marked heterogeneity between families and between individuals. T-cell response magnitude is associated with male sex and older age by multiple linear regression. SARS-CoV-2-specific T-cell responses in seronegative individuals are widespread, particularly in adults and in individuals exposed to SARS-CoV-2 through an infected family member. The magnitude of this response is associated with the number of seropositive family members, with a greater number of seropositive individuals within a family leading to stronger T-cell immunity in seronegative individuals. Discussion: These results support a model whereby exposure to SARS-CoV-2 promotes T-cell immunity in the absence of an antibody response. The source of these seronegative T-cell responses to SARS-CoV-2 has been suggested as cross-reactive immunity to endemic coronaviruses that is expanded upon SARS-CoV-2 exposure. However, in this study, no association between HCoV-specific immunity and seronegative T-cell immunity to SARS-CoV-2 is identified, suggesting that de novo T-cell immunity may be generated in seronegative SARS-CoV-2 exposed individuals.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Additional Information: License information from Publisher: LICENSE 1: URL:
Publisher: Frontiers Media
Date of First Compliant Deposit: 14 September 2023
Date of Acceptance: 11 August 2023
Last Modified: 15 Sep 2023 00:13

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