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Exposed seronegative: Cellular immune responses to SARS-CoV-2 in the absence of seroconversion.
Jay, Cecilia; Ratcliff, Jeremy; Turtle, Lance; Goulder, Philip; Klenerman, Paul.
  • Jay C; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Ratcliff J; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Turtle L; National Institute for Health and Care Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, United Kingdom.
  • Goulder P; Peter Medawar Building for Pathogen Research, Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
  • Klenerman P; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Front Immunol ; 14: 1092910, 2023.
Article in English | MEDLINE | ID: covidwho-2231410
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Hepatitis C / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Humans Language: English Journal: Front Immunol Year: 2023 Document Type: Article Affiliation country: Fimmu.2023.1092910

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Hepatitis C / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Humans Language: English Journal: Front Immunol Year: 2023 Document Type: Article Affiliation country: Fimmu.2023.1092910