Remdesivir Modulates CASP8 and CASP9 Expression in COVID-19 Patients: Impact on Apoptotic Pathways and Immune Response

Introduction: COVID-19, caused by SARS-CoV-2, is associated with alterations in apoptotic signaling pathways, which influence disease progression and immune function. CASP8 and CASP9 are key regulators of apoptosis. This study aimed to evaluate the expression levels of the CASP8 and CASP9 genes in COVID-19 patients compared to healthy controls, and to investigate the effect of Remdesivir treatment on their expression. Methods: Blood samples were collected from 30 hospitalized patients infected with the SARS-CoV-2 Omicronvariant before and after Remdesivir treatment, and from 20 healthy controls. Patients received intravenous Remdesivir therapy (200 mg on day one, followed by 100 mg daily for 4 days). RNA was extracted from blood leukocytes, and real-time quantitative PCR (qPCR) was conducted to assess gene expression, normalized to GAPDH. Results: No significant difference was observed in CASP8 expression between untreated COVID-19 patients and controls. However, CASP8 expression increased 2.5-fold in Remdesivir-treated COVID-19 patients compared to untreated patients (P < 0.001). CASP9 expression was reduced to 10% of healthy control levels in COVID-19 patients (P < 0.001) but increased to 80% of control values after Remdesivir therapy (P < 0.001). A modest positive correlation was observed between CASP8 and CASP9 expression (r = 0.333; P = 0.05), and between CASP8 expression and total white blood cell (WBC) count (r = 0.356; P = 0.05). Conclusions: Remdesivir modulates apoptosis-related gene expression, upregulating CASP8 and partially restoring CASP9 expression in COVID-19 patients. These findings suggest that Remdesivir influences apoptotic pathways, which may contribute to immune regulation during SARS-CoV-2 infection and enhance therapeutic outcomes.