Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion

Jay, Cecilia, Ratcliff, Jeremy, Turtle, Lance ORCID: 0000-0002-0778-1693, Goulder, Philip and Klenerman, Paul
(2023) Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion. FRONTIERS IN IMMUNOLOGY, 14. 1092910-.

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The factors determining whether infection will occur following exposure to SARS-CoV-2 remain elusive. Certain SARS-CoV-2-exposed individuals mount a specific T-cell response but fail to seroconvert, representing a population that may provide further clarity on the nature of infection susceptibility and correlates of protection against SARS-CoV-2. Exposed seronegative individuals have been reported in patients exposed to the blood-borne pathogens Human Immunodeficiency virus and Hepatitis C virus and the sexually transmitted viruses Hepatitis B virus and Herpes Simplex virus. By comparing the quality of seronegative T-cell responses to SARS-CoV-2 with seronegative cellular immunity to these highly divergent viruses, common patterns emerge that offer insights on the role of cellular immunity against infection. For both SARS-CoV-2 and Hepatitis C, T-cell responses in exposed seronegatives are consistently higher than in unexposed individuals, but lower than in infected, seropositive patients. Durability of T-cell responses to Hepatitis C is dependent upon repeated exposure to antigen - single exposures do not generate long-lived memory T-cells. Finally, exposure to SARS-CoV-2 induces varying degrees of immune activation, suggesting that exposed seronegative individuals represent points on a spectrum rather than a discrete group. Together, these findings paint a complex landscape of the nature of infection but provide clues as to what may be protective early on in SARS-CoV-2 disease course. Further research on this phenomenon, particularly through cohort studies, is warranted.

Item Type: Article
Uncontrolled Keywords: SARS-CoV-2, seronegative, T-cells, exposed, hepatitis C
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 19 Apr 2023 16:59
Last Modified: 19 Apr 2023 16:59
DOI: 10.3389/fimmu.2023.1092910
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