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Journal article : Review

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

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fimmu.2023.1092910

Authors


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Role:
Author
ORCID:
0000-0002-0778-1693
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Paediatrics
Oxford college:
Brasenose College
Role:
Author
ORCID:
0000-0002-9842-4674
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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Oxford college:
Green Templeton College
Role:
Author
ORCID:
0000-0003-4307-9161


Publisher:
Frontiers Media
Journal:
Frontiers in Immunology More from this journal
Volume:
14
Article number:
1092910
Place of publication:
Switzerland
Publication date:
2023-01-26
Acceptance date:
2023-01-16
DOI:
EISSN:
1664-3224
Pmid:
36776841


Language:
English
Keywords:
Subtype:
Review
Pubs id:
1329077
Local pid:
pubs:1329077
Deposit date:
2023-10-17

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