2. Academic Validation
  3. T cell apoptosis characterizes severe Covid-19 disease

T cell apoptosis characterizes severe Covid-19 disease

  • Cell Death Differ. 2022 Aug;29(8):1486-1499. doi: 10.1038/s41418-022-00936-x.
Sonia André 1,  Morgane Picard 1,  Renaud Cezar 2,  Florence Roux-Dalvai 3 4,  Aurélie Alleaume-Butaux 1 5,  Calaiselvy Soundaramourty 1,  André Santa Cruz 6 7 8,  Ana Mendes-Frias 6 7,  Clarisse Gotti 3 4,  Mickaël Leclercq 3 4,  Alexandre Nicolas 1,  Alexandra Tauzin 1,  Alexandre Carvalho 6 7 8,  Carlos Capela 6 7 8,  Jorge Pedrosa 6 7,  António Gil Castro 6 7,  Lucy Kundura 9,  Paul Loubet 10,  Albert Sotto 10,  Laurent Muller 11,  Jean-Yves Lefrant 11,  Claire Roger 11,  Pierre-Géraud Claret 12,  Sandra Duvnjak 13,  Tu-Anh Tran 14,  Gina Racine 15,  Ouafa Zghidi-Abouzid 15,  Pierre Nioche 1 5,  Ricardo Silvestre 6 7,  Arnaud Droit 3 4,  Fabrizio Mammano 1,  Pierre Corbeau 16 17,  Jérôme Estaquier 18 19
Affiliations

Affiliations

  • 1 INSERM-U1124, Université Paris, Paris, France.
  • 2 Laboratoire d'Immunologie, CHU de Nîmes, Nîmes, France.
  • 3 Proteomics platform, CHU de Québec - Université Laval Research Center, Québec City, Québec, Canada.
  • 4 Computational Biology Laboratory, CHU de Québec - Université Laval Research Center, Québec City, Québec, Canada.
  • 5 Structural and Molecular Analysis Platform, BioMedTech Facilities INSERM US36-CNRS UMS2009, Université Paris, Paris, France.
  • 6 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
  • 7 ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
  • 8 Department of Internal Medicine, , Hospital of Braga, Braga, Portugal.
  • 9 Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, Montpellier, France.
  • 10 Service des Maladies Infectieuses et Tropicales, CHU de Nîmes, Nîmes, France.
  • 11 Service de Réanimation Chirugicale, CHU de Nîmes, Nîmes, France.
  • 12 Urgences Médico-Chirugicales Hospitalisation, CHU de Nîmes, Nîmes, France.
  • 13 Service de Gérontologie et Prévention du Vieillissement, CHU de Nîmes, Nîmes, France.
  • 14 Service de Pédiatrie, CHU de Nîmes, Nîmes, France.
  • 15 CHU de Québec - Université Laval Research Center, Québec City, Québec, Canada.
  • 16 Laboratoire d'Immunologie, CHU de Nîmes, Nîmes, France. pierre.corbeau@igh.cnrs.fr.
  • 17 Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, Montpellier, France. pierre.corbeau@igh.cnrs.fr.
  • 18 INSERM-U1124, Université Paris, Paris, France. estaquier@yahoo.fr.
  • 19 CHU de Québec - Université Laval Research Center, Québec City, Québec, Canada. estaquier@yahoo.fr.
PMID: 35066575 DOI: 10.1038/s41418-022-00936-x
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.

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