T cell apoptosis characterizes severe Covid-19 disease
Sónia André, Morgane Picard, Renaud Cezar, Florence Roux‐Dalvai, Aurélie Alleaume‐Butaux, Calaiselvy Soundaramourty, André Santa Cruz, Ana Mendes‐Frias, Clarisse Gotti, Mickaël Leclercq, Alexandre Nicolas, Alexandra Tauzin, Alexandre Carvalho, Carlos Capela, Jorge Pedrosa, António G. Castro, Lucy Kundura, Paul Loubet, Albert Sotto, Laurent Müller, Jean‐Yves Lefrant, Claire Roger, Pierre‐Géraud Claret, Sandra Duvnjak, Tú-Anh Tran, Gina Racine, Ouafa Zghidi‐Abouzid, Pierre Nioche, Ricardo Silvestre, Arnaud Droit, Fabrizio Mammano, Pierre Corbeau, Jérôme Estaquier
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.