Angiotensin-Converting Enzyme 1 (ACE1) gene polymorphisms in pediatric patients with COVID-19: impact on disease severity and outcomes

Angiotensin-converting enzyme 1 ( ACE1 ) gene polymorphisms have been suggested to influence susceptibility to and severity of coronavirus disease 2019 (COVID-19) through dysregulation of the renin–angiotensin system. Despite considerable research on COVID-19, the influence of genetic factors, particularly polymorphisms in the ACE gene, on disease severity in pediatric populations remains inadequately understood. Therefore, the present study aimed to investigate the association of ACE1 insertion/deletion (I/D) polymorphism and ACE1 variants rs4341 and rs4343 with clinical manifestations, laboratory findings, and disease severity in hospitalized children with COVID-19. This study included 100 hospitalized pediatric patients with confirmed COVID-19 infection. Demographic characteristics, including age and sex, clinical manifestations, comorbidities, disease severity, laboratory findings, ICU hospitalization, and mortality outcomes were recorded. Genotyping of the ACE1 I/D polymorphism was performed using PCR-based methods, while rs4341 (C/G) and rs4343 (A/G) polymorphisms were analyzed using PCR-restriction fragment length polymorphism (PCR-RFLP) assays. Among the 100 enrolled patients, 76% had mild/moderate disease and 24% had severe disease. The ACE1 D/D genotype was identified in 76% of patients, whereas the ACE1 I/I genotype was detected in only 3% of cases. In the analysis of the rs4341 polymorphism, among 77 successfully genotyped patients, the C/C genotype was predominant and identified in 56 out of 77 (73.7%) individuals, while the C/G genotype was observed in 20 out of 77 (26.3%) patients. Severe disease was observed in 34 out of 56 (61%) individuals carrying the rs4341 C/C genotype compared with 8 out of 20 (40%) individuals with the C/G genotype; however, the difference was not statistically significant ( P = 0.12). Patients carrying the rs4343 A/A genotype exhibited significantly higher white blood cell counts [8.2 (5.7–11.9) ×10⁹ cells/L vs. 5.5 (4.2–7.8) ×10⁹ cells/L, P = 0.008], platelet counts [269 (220.2–332) ×10⁹ cells/L vs. 206 (161.5–300) ×10⁹ cells/L, P = 0.041], and lactate dehydrogenase levels [555.5 (494.8–601.7) U/L vs. 461 (403–593.7) U/L, P = 0.011] compared with rs4343 A/G carriers. In conclusion, although the ACE1 D/D genotype was highly prevalent among pediatric COVID-19 patients, it was not significantly associated with disease severity or ICU hospitalization. Similarly, no significant associations were identified between rs4341 or rs4343 polymorphisms and overall clinical outcomes. However, rs4343 variants were associated with differences in laboratory parameters, including WBC count, platelet count, and LDH levels, suggesting a possible role in host inflammatory responses during SARS-CoV-2 infection. These findings should be interpreted cautiously due to the relatively small sample size and lack of a healthy control group.