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- Title
Low perforin expression in CD8+ T lymphocytes during the acute phase of severe SARS-CoV-2 infection predicts long COVID.
- Authors
Kundura, Lucy; Cezar, Renaud; André, Sonia; Campos-Mora, Mauricio; Lozano, Claire; Vincent, Thierry; Muller, Laurent; Lefrant, Jean-Yves; Roger, Claire; Claret, Pierre-Geraud; Duvnjak, Sandra; Loubet, Paul; Sotto, Albert; Tu-Ahn Tran; Estaquier, Jérôme; Corbeau, Pierre
- Abstract
T cell cytotoxicity plays a major role in antiviral immunity. Anti-SARS-CoV-2 immunity may determine acute disease severity, but also the potential persistence of symptoms (long COVID). We therefore measured the expression of perforin, a cytotoxic mediator, in T cells of patients recently hospitalized for SARS-CoV-2 infection. We recruited 54 volunteers confirmed as being SARS-CoV-2-infected by RT-PCR and admitted to Intensive Care Units (ICUs) or non-ICU, and 29 age- and sex-matched healthy controls (HCs). Amounts of intracellular perforin and granzyme-B, as well as cell surface expression of the degranulation marker CD107A were determined by flow cytometry. The levels of 15 cytokines in plasma were measured by Luminex. The frequency of perforin-positive T4 cells and T8 cells was higher in patients than in HCs (9.9 ± 10.1% versus 4.6 ± 6.4%, p = 0.006 and 46.7 ± 20.6% vs 33.3 ± 18.8%, p = 0.004, respectively). Perforin expression was neither correlated with clinical and biological markers of disease severity nor predictive of death. By contrast, the percentage of perforin-positive T8 cells in the acute phase of the disease predicted the onset of long COVIDone year later. A lowT8 cytotoxicity in the first days of SARS-CoV-2 infection might favor virus replication and persistence, autoimmunity, and/or reactivation of other viruses such as Epstein-Barr virus or cytomegalovirus, paving the way for long COVID. Under this hypothesis, boosting T cell cytotoxicity during the acute phase of the infection could prevent delayed sequelae.
- Subjects
POST-acute COVID-19 syndrome; T cells; PERFORINS; SARS-CoV-2; CD8 antigen
- Publication
Frontiers in Immunology, 2022, Vol 13, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2022.1029006