T cell apoptosis characterizes severe Covid-19 disease.
Sonia AndréMorgane PicardRenaud CezarFlorence Roux-DalvaiAurélie Alleaume-ButauxCalaiselvy SoundaramourtyAndré Santa CruzAna Mendes-FriasClarisse GottiMickaël LeclercqAlexandre NicolasAlexandra TauzinAlexandre CarvalhoCarlos CapelaJorge PedrosaAntónio Gil CastroLucy KunduraPaul LoubetAlbert SottoLaurent MullerJean-Yves LefrantClaire RogerPierre-Géraud ClaretSandra DuvnjakTu-Anh TranGina RacineOuafa Zghidi-AbouzidPierre NiocheRicardo SilvestreArnaud DroitFabrizio MammanoPierre CorbeauJérome EstaquierPublished in: Cell death and differentiation (2022)
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.
Keyphrases
- sars cov
- cell death
- intensive care unit
- cell cycle arrest
- respiratory syndrome coronavirus
- coronavirus disease
- cell surface
- mechanical ventilation
- early onset
- cell proliferation
- oxidative stress
- healthcare
- poor prognosis
- hiv aids
- drug induced
- hiv infected
- endoplasmic reticulum stress
- hiv positive
- human immunodeficiency virus
- hiv testing
- kidney transplantation
- long non coding rna
- south africa