en Microbial pathogenesis Microbial pathogenesis Original article Original article <b><span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">Introduction</span></span></span></b><span style="font-size:10.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">: COVID-19, caused by SARS-CoV-2, is associated with alterations in apoptotic signaling pathways, which influence disease progression and immune function. <i>CASP8</i> and <i>CASP9</i> are key regulators of apoptosis. This study aimed to evaluate the expression levels of the <i>CASP8</i> and <i>CASP9</i> genes in COVID-19 patients compared to healthy controls, and to investigate the effect of Remdesivir treatment on their expression. <b>Methods</b>: Blood samples were collected from 30 hospitalized patients infected with the SARS-CoV-2 Omicron variant 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 <i>GAPDH</i>. <b>Results</b>: No significant difference was observed in <i>CASP8</i> expression between untreated COVID-19 patients and controls. However, <i>CASP8</i> expression increased 2.5-fold in Remdesivir-treated COVID-19 patients compared to untreated patients (<i>P</i> < 0.001). <i>CASP9</i> expression was reduced to 10% of healthy control levels in COVID-19 patients (<i>P</i> < 0.001) but increased to 80% of control values after Remdesivir therapy (<i>P</i> < 0.001). A modest positive correlation was observed between <i>CASP8</i> and <i>CASP9</i> expression (r = 0.333; <i>P</i> = 0.05), and between <i>CASP8</i> expression and total white blood cell (WBC) count (r = 0.356; <i>P</i> = 0.05). <b>Conclusions</b>: Remdesivir modulates apoptosis-related gene expression, upregulating <i>CASP8</i> and partially restoring <i>CASP9</i> 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.</span></span></span> CASP8, CASP9, Apoptotic pathways, Remdesivir, COVID-19 118 126 http://jommid.pasteur.ac.ir/browse.php?a_code=A-10-646-1&slc_lang=en&sid=1 Sohameh Mohebbi s.mohebbi@aletaha.ac.ir 0000-0002-4512-175X Yes Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran Somayeh Arabzadeh s.arabzadeh@aletaha.ac.ir 0000-0002-7330-8271 No Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran Sara Naseri Lahiji saranaseri7560@gmail.com 0009-0006-1824-9826 No Department of Biology, Faculty of Basic Science, Ale Taha Institute of Higher Education, Tehran, Iran Zahra Fathi ILAR23@YAHOO.COM 0009-0003-4294-3381 No Department of Genetics, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran