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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.<\/jats:p>","DOI":"10.1038\/s41418-022-00936-x","type":"journal-article","created":{"date-parts":[[2022,1,22]],"date-time":"2022-01-22T05:02:34Z","timestamp":1642827754000},"page":"1486-1499","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":148,"title":["T cell apoptosis characterizes severe Covid-19 disease"],"prefix":"10.1038","volume":"29","author":[{"given":"Sonia","family":"Andr\u00e9","sequence":"first","affiliation":[]},{"given":"Morgane","family":"Picard","sequence":"additional","affiliation":[]},{"given":"Renaud","family":"Cezar","sequence":"additional","affiliation":[]},{"given":"Florence","family":"Roux-Dalvai","sequence":"additional","affiliation":[]},{"given":"Aur\u00e9lie","family":"Alleaume-Butaux","sequence":"additional","affiliation":[]},{"given":"Calaiselvy","family":"Soundaramourty","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9 Santa","family":"Cruz","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Mendes-Frias","sequence":"additional","affiliation":[]},{"given":"Clarisse","family":"Gotti","sequence":"additional","affiliation":[]},{"given":"Micka\u00ebl","family":"Leclercq","sequence":"additional","affiliation":[]},{"given":"Alexandre","family":"Nicolas","sequence":"additional","affiliation":[]},{"given":"Alexandra","family":"Tauzin","sequence":"additional","affiliation":[]},{"given":"Alexandre","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Capela","sequence":"additional","affiliation":[]},{"given":"Jorge","family":"Pedrosa","sequence":"additional","affiliation":[]},{"given":"Ant\u00f3nio Gil","family":"Castro","sequence":"additional","affiliation":[]},{"given":"Lucy","family":"Kundura","sequence":"additional","affiliation":[]},{"given":"Paul","family":"Loubet","sequence":"additional","affiliation":[]},{"given":"Albert","family":"Sotto","sequence":"additional","affiliation":[]},{"given":"Laurent","family":"Muller","sequence":"additional","affiliation":[]},{"given":"Jean-Yves","family":"Lefrant","sequence":"additional","affiliation":[]},{"given":"Claire","family":"Roger","sequence":"additional","affiliation":[]},{"given":"Pierre-G\u00e9raud","family":"Claret","sequence":"additional","affiliation":[]},{"given":"Sandra","family":"Duvnjak","sequence":"additional","affiliation":[]},{"given":"Tu-Anh","family":"Tran","sequence":"additional","affiliation":[]},{"given":"Gina","family":"Racine","sequence":"additional","affiliation":[]},{"given":"Ouafa","family":"Zghidi-Abouzid","sequence":"additional","affiliation":[]},{"given":"Pierre","family":"Nioche","sequence":"additional","affiliation":[]},{"given":"Ricardo","family":"Silvestre","sequence":"additional","affiliation":[]},{"given":"Arnaud","family":"Droit","sequence":"additional","affiliation":[]},{"given":"Fabrizio","family":"Mammano","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8576-6683","authenticated-orcid":false,"given":"Pierre","family":"Corbeau","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-8044","authenticated-orcid":false,"given":"J\u00e9r\u00f4me","family":"Estaquier","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,1,22]]},"reference":[{"key":"936_CR1","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1126\/science.abm4454","volume":"374","author":"M Worobey","year":"2021","unstructured":"Worobey M. 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