Journal
CELL DEATH AND DIFFERENTIATION
Volume 29, Issue 8, Pages 1486-1499Publisher
SPRINGERNATURE
DOI: 10.1038/s41418-022-00936-x
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Categories
Funding
- Fondation Recherche Medicale
- Agence Nationale de la Recherche (COVID-I2A)
- Nimes University Hospital [NIMAO/2020/COVID/PC-01]
- Foundation for Science and Technology (FCT) [UIDB/50026/2020, UIDP/50026/2020]
- Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) [NORTE-01-0145-FEDER-000013, NORTE-01-0145-FEDER-000023]
- FCT [UMINHO/BD/57/2018]
- Fundacao para a Ciencia e Tecnologia (FCT)
- Research and Innovation Chair L'Oreal in Digital Biology
- Canada Research Chair program
- Abbvie France
- Abbvie Canada
- AMF
- [IF/00021/2014]
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By comparing COVID-19 patients with healthy donors, the study found a strong correlation between T cell apoptosis and lymphopenia in severe cases. The plasma levels of soluble FasL (sFasL) and T cell surface expression of Fas/CD95 were positively correlated with T cell death and CD4 T cell counts. The study also identified modulations in the Bcl-2 family and demonstrated the potential of a pan-caspase inhibitor, Q-VD, to prevent T cell apoptosis and enhance Th1 transcripts.
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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