T cell apoptosis characterizes severe Covid-19 disease

Cell Death Differ. 2022 Aug;29(8):1486-1499. doi: 10.1038/s41418-022-00936-x. Epub 2022 Jan 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CD4-Positive T-Lymphocytes / metabolism
  • COVID-19*
  • Caspases / metabolism
  • Fas Ligand Protein
  • Humans
  • Lymphopenia*
  • SARS-CoV-2
  • T-Lymphocytes / metabolism
  • fas Receptor / metabolism


  • Fas Ligand Protein
  • fas Receptor
  • Caspases