Remdesivir Modulates CASP۸ and CASP۹ Expression in COVID-۱۹ Patients: Impact on Apoptotic Pathways and Immune Response

Introduction: COVID-۱۹, caused by SARS-CoV-۲, is associated with alterations in apoptotic signaling pathways, which influence disease progression and immune function. CASP۸ and CASP۹ are key regulators of apoptosis. This study aimed to evaluate the expression levels of the CASP۸ and CASP۹ genes in COVID-۱۹ patients compared to healthy controls, and to investigate the effect of Remdesivir treatment on their expression. Methods: Blood samples were collected from ۳۰ hospitalized patients infected with the SARS-CoV-۲ Omicron variant before and after Remdesivir treatment, and from ۲۰ healthy controls. Patients received intravenous Remdesivir therapy (۲۰۰ mg on day one, followed by ۱۰۰ mg daily for ۴ 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 CASP۸ expression between untreated COVID-۱۹ patients and controls. However, CASP۸ expression increased ۲.۵-fold in Remdesivir-treated COVID-۱۹ patients compared to untreated patients (P < ۰.۰۰۱). CASP۹ expression was reduced to ۱۰% of healthy control levels in COVID-۱۹ patients (P < ۰.۰۰۱) but increased to ۸۰% of control values after Remdesivir therapy (P < ۰.۰۰۱). A modest positive correlation was observed between CASP۸ and CASP۹ expression (r = ۰.۳۳۳; P = ۰.۰۵), and between CASP۸ expression and total white blood cell (WBC) count (r = ۰.۳۵۶; P = ۰.۰۵). Conclusions: Remdesivir modulates apoptosis-related gene expression, upregulating CASP۸ and partially restoring CASP۹ expression in COVID-۱۹ patients. These findings suggest that Remdesivir influences apoptotic pathways, which may contribute to immune regulation during SARS-CoV-۲ infection and enhance therapeutic outcomes.

کلیدواژه ها:

CASP۸ ، CASP۹ ، Apoptotic pathways ، Remdesivir ، COVID-۱۹