<b><i>Introduction:</i></b> The prevalence of coronavirus disease 2019 (COVID-19) has rapidly increased worldwide. More investigation is needed to progress toward understanding the exact role of immune responses in the pathology of the disease, leading to improved anticipation and treatment options. <b><i>Methods:</i></b> In the present study, we examined the relative expression of T-bet, GATA3, RORγt, and FoxP3 transcription factors as well as laboratory indicators in 79 hospitalized patients along with 20 healthy subjects as a control group. In order to make an exact comparison between various degrees of severity of disease, patients were divided into critical (<i>n</i> = 12) and severe (<i>n</i> = 67) groups. To evaluate the expression of genes of interest by performing real-time PCR, blood samples were obtained from each participant. <b><i>Results:</i></b> We found a significant increase in the expression of T-bet, GATA3, and RORγt and a reduction in the expression of FoxP3 in the critically ill patients compared to the severe and control groups. Also, we noticed that the GATA3 and RORγt expressions were elevated in the severe group in comparison with healthy subjects. Additionally, the GATA3 and RORγt expressions showed a positive correlation with elevation in CRP and hepatic enzyme concentration. Moreover, we observed that the GATA3 and RORγt expressions were the independent risk factors for the severity and outcome of COVID-19. <b><i>Discussion:</i></b> The present study showed that the overexpression of T-bet, GATA3, and RORγt, as well as a decrease in the FoxP3 expression was associated with the severity and fatal outcome of COVID-19.