T cell apoptosis characterizes severe Covid-19 disease PMID: 35066575

ADC Targets in Oncology

2026-04-10

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

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. [email protected].
17. Institut de Génétique Humaine UMR9002 CNRS-Université de Montpellier, Montpellier, France. [email protected].
18. INSERM-U1124, Université Paris, Paris, France. [email protected].
19. CHU de Québec - Université Laval Research Center, Québec City, Québec, Canada. [email protected].

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.