T cell apoptosis characterizes severe Covid-19 disease.
Cell Death Differ
; 29(8): 1486-1499, 2022 08.
Article
in English
| MEDLINE | ID: covidwho-1641945
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
COVID-19
/
Lymphopenia
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Cell Death Differ
Year:
2022
Document Type:
Article
Affiliation country:
S41418-022-00936-x
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