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.
【저자키워드】 Microbiology, Immune cell death, 【초록키워드】 SARS-CoV-2, Apoptosis, HIV, Biomarker, intensive care, severe COVID-19, CXCL10, knowledge, SARS-COV-2 infection, disease severity, Th1, immunodeficiency, CD4, ICU, lymphopenia, T cell, ROC, pathophysiology, death, plasma, T-cell, inhibitor, expression, mechanism, caspase, COVID-19 patients, COVID-19 patient, Activation, Bcl-2 family, healthy donors, individual, positive correlation, non-ICU, transcripts, Prevent, ENhance, involved, characterized, demonstrated, correlated, modulated, Plasma level, 【제목키워드】 Apoptosis, T cell, disease,