The COVID-19 pandemic caused by SARS-CoV-2 is influenced by genetic and epigenetic factors, including miR-155, which affects immune cell and virus functions and laboratory biomarkers. This study evaluates miR-155's role as a biomarker for SARS-CoV-2 detection and monitoring, examining its significance in identifying infection in both vaccinated and unvaccinated individuals using ROC curve analysis. Among the miRNAs, miRNA-155 (miR-155) has been thoroughly examined in individuals with SARS-CoV-2 that is either severe or mild. According to reports, people infected with SARS-CoV-2 may be instructed to trigger a cytokine storm or strong pro-inflammatory reactions. CRP and miR-155 exhibited a strong and positive correlation, Consequently, the molecules have the capacity to control the expression of the viral and immune system proteins inside the host cells. Based on these findings, MiR-155 has been shown to have a major role in the pathophysiology and severity of SARS-CoV-2, and it may be used as a clinical biomarker for early infection severity and detections