Background:  Key actors in SARS-CoV-2 entrance into host cells include angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). Our objective was to study gene expression of those key actors in COVID-19 patients, with especial emphasis on patients having other comorbidities. Methods: The Expression of ACE2 and TMPRSS2 genes in nasopharyngeal swabs was assessed in 84 COVID-19 patients in comparison with 30 healthy controls using real-time PCR. We also compared expression levels of ACE2 and TMPRSS2 between different COVID-19 groups; moderate & severe, diabetic & non-diabetic, hypertensive & normotensive individuals, and between individuals belonging to different age groups. Results: Our results showed that up-regulation of ACE2 and TMPRSS2 was observed in COVID-19 patients relative to healthy controls, and there was a positive correlation between ACE2 and TMPRSS2 expression levels. TMPRSS2 gene expression level was higher in older age groups and both genes showed higher expression levels in males. On the other hand, no difference was detected in the gene expression level of ACE2 and TMPRSS2 between moderate and severe COVID-19 patients. Also, alterations were detected in the two genes expression levels in patients having comorbidities. Conclusions: The ACE2 and TMPRSS2 gene expression levels varied between different patient groups, posing a greater risk of getting SARS-CoV2 infection.