CASPASE-3 expression and activity in PBMCs associate with SARS-CoV-2 infection and clinical features

Background: Although vaccines and treatments exist, new SARS-CoV-2 variants continue to emerge. An imbalance between apoptosis and autophagy may contribute to COVID-19 pathogenesis, leading to tissue damage and inflammation. Objective: To investigate the role of cell death-related proteins during SARS-CoV-2 infection and their associations with clinical variables. Methods: A total of 140 samples were analyzed (n = 73 infected, n = 67 uninfected). Gene expression of apoptotic and autophagic markers was evaluated by RT-qPCR in peripheral blood mononuclear cells. Caspase 3/7 activity was assessed using flow cytometry. Results: Infected patients showed higher expression of CASPASE 3, BID (p < 0.05), and MAP1LC3 (p < 0.01). CASPASE 3 expression was higher in variant omicron, male sex, high viral load, and various clinical symptoms. Caspase 3/7 activity increased in CD4⁺ T and B cells of individuals infected with SARS-CoV-2. Conclusions: Although our previous results with CASPASE 3 are promising and suggest that it may become a potential therapeutic target, additional studies are needed to confirm these hypotheses and evaluate potential intervention strategies.