Introduction: Angiotensin-converting enzyme 2 (ACE2) is a receptor with a high affinity for the COVID-19 virus and its gene expression varies across different tissues and individuals. Variations in ACE2 gene expression have been linked to disease severity, particularly in individuals with immune conditions such as Multiple Sclerosis (MS). Methodology: Participants were divided into four Groups; Group A (hospitalized severe patients), Group B (outpatients with mild COVID-19 symptoms), Group C (healthy individuals), and Group D (patients with MS). Following RNA extraction and cDNA synthesis, ACE2 gene expression levels were measured using Real-time PCR. Correlations between ACE2 expression, age, and sex were analyzed. Results: ACE2 gene expression was significantly elevated in Groups A (3.52±1.45) and B (2.54±1.345) compared to Groups C (0.33±0.13) and D (0.90±1.45). There were also significant differences between most of the studied Groups. A significant positive correlation was also found between ACE2 gene expression and age (r = 0.368, p < 0.001), suggesting a moderate yet robust relationship. Conclusions: The highest level of ACE2 gene expression was observed in Group A, while Group B exhibited lower ACE2 expression. Groups C and D showed the lowest ACE2 expression level. These findings suggest that ACE2 gene expression is a potential marker for COVID-19 severity and may provide insights into the interplay between COVID-19, MS, age, and sex.