Background: Suppression of the renin-angiotensin system by SARS-CoV-2 binding changes the balance between ACE and ACE2, which affects blood pressure regulation. The ACE gene polymorphisms in intron 16 are associated with susceptibility to SARS-CoV-2 infection in patients with hypertension. Objective: This study analyzed the ACE gene polymorphism distribution and determined the probability of infection and severity of hypertension in COVID-19 patients. Methods: One hundred and six adult subjects were involved in this cross-sectional study, comprising 95 COVID-19 subjects and 91 non-COVID-19 subjects from two parts of Indonesia in 2021, i.e. Palu City, Central Celebes, and Lahat District, South Sumatra, DNAs extracted from whole blood were analyzed for I/D polymorphisms by Polymerase Chain Reaction (PCR) method. Results: Distribution of ACE genotypes were found as follows; II (53%), ID (38%), and DD (9%). The percentage of hypertension and the severity of COVID-19 in the Palu population were higher than those in Lahat District, i.e., 44% vs. 14% and 80% vs. 46%, respectively. Although there was no significant association between the I/D genotypes and susceptibility or severity of COVID-19 (p> 0.05), it appeared that subjects with hypertension and dyspnea symptoms were five times more susceptible to a moderate-severe symptom that required hospitalization and was associated with a fivefold increase in the risk of dyspnea symptoms that required hospitalization. However, comorbid hypertension was associated with moderate to severe COVID-19 (p=0.007). Conclusion: It can be assumed that in our studied population, ACE gene I/D polymorphisms and hypertension are not associated with susceptibility to SARS-CoV-2 infection, but the presence of comorbid hypertension is a risk factor for more severe COVID-19. © the Authors.