1. T cell apoptosis characterizes severe Covid-19 disease
- Author
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André, Sonia, Picard, Morgane, Cezar, Renaud, Roux-Dalvai, Florence, Alleaume-Butaux, Aurélie, Soundaramourty, Calaiselvy, Cruz, André Santa, Mendes-Frias, Ana, Gotti, Clarisse, Leclercq, Mickaël, Nicolas, Alexandre, Tauzin, Alexandra, Carvalho, Alexandre, Capela, Carlos, Pedrosa, Jorge, Castro, António Gil, Kundura, Lucy, Loubet, Paul, Sotto, Albert, Muller, Laurent, Lefrant, Jean-Yves, Roger, Claire, Claret, Pierre-Géraud, Duvnjak, Sandra, Tran, Tu-Anh, Racine, Gina, Zghidi-Abouzid, Ouafa, Nioche, Pierre, Silvestre, Ricardo, Droit, Arnaud, Mammano, Fabrizio, Corbeau, Pierre, and Estaquier, Jérôme
- Abstract
Severe SARS-CoV-2 infections are characterized by lymphopenia, but the mechanisms involved are still elusive. Based on our knowledge of HIV pathophysiology, we hypothesized that SARS-CoV-2 infection-mediated lymphopenia could also be related to T cell apoptosis. By comparing intensive care unit (ICU) and non-ICU COVID-19 patients with age-matched healthy donors, we found a strong positive correlation between plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 with the propensity of T cells to die and CD4 T cell counts. Plasma levels of sFasL and T cell death are correlated with CXCL10 which is part of the signature of 4 biomarkers of disease severity (ROC, 0.98). We also found that members of the Bcl-2 family had modulated in the T cells of COVID-19 patients. More importantly, we demonstrated that the pan-caspase inhibitor, Q-VD, prevents T cell death by apoptosis and enhances Th1 transcripts. Altogether, our results are compatible with a model in which T-cell apoptosis accounts for T lymphopenia in individuals with severe COVID-19. Therefore, a strategy aimed at blocking caspase activation could be beneficial for preventing immunodeficiency in COVID-19 patients.
- Published
- 2022
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