Ab0276 Peculiarities of the Course of Covid-19 and Allelic Polymorphism Rs4646994 of the Ace1 Gene in Juvenile Idiopathic Arthritis

Background: Currently, there are no statistically significant data on the determination of risk factors and the role of the rs4646994 polymorphism in predicting the severity of COVID-19 in juvenile idiopathic arthritis (JIA). Objectives: To study the features of the clinical course of COVID-19 and the role of the allelic polymorphism rs 4646994 of the ACE1 gene for the prevention and personalized therapy of patients with JIA. Methods: We analyzed the anamnestic and clinical data of 44 patients with JIA who had COVID-19, the average age of children was (9.47±4.2) years. There were 2 groups of patients: I - 31 (70.5%) children with mild and asymptomatic course, II - 13 (29.5%) children with moderate COVID-19. The control group consisted of 20 children with mild and asymptomatic COVID-19 without chronic somatic pathology. The isolation and purification of genomic DNA preparations using proteinase K were performed, which constituted the Patient Biobank for genotyping at rs4646994 of the ACE1 gene. Results: COVID-19 infection in 70.5% of patients with JIA has a mild, subclinical course. Insufficient medical control of the underlying autoimmune disease may be a predicted risk factor for more severe COVID-19 [OR 4.29±0.85 (DI (1.2-22.9)], (p=0.03). When studying the distribution of ACE I/D genotypes and alleles in JIA depending on the severity of coronavirus infection, no significant difference was found in the groups. However, there was a tendency to increase the frequency of the genotype (II insertion) among patients with JIA who had mild COVID-19 compared with the control group. In genotype II, there is, on the one hand, an imbalance of components of the renin-angiotensin system, which leads to the development of inflammatory processes characteristic of this autoimmune disease, but, on the other hand, genotype II can be considered as a protective factor, which causes a milder course of COVID-19 in this category of patients. In contrast to studies conducted in adult patients, no association has been established in children between the severity of COVID-19 disease and the carriage of the D allele of the ACE1 gene. The lack of data on such an association in the studied groups of children can be explained by the fact that there is evidence of a lower level of ACE2 expression in children than in adults, as well as a different tissue-specific localization of active ACE2 molecules and, accordingly, the systemically associated ACE1 protein level, depending on the genotype. The development, distribution and function of ACE2 protein in children may differ from that observed in adults. Studies have shown that the intracellular response induced by ACE2 in alveolar epithelial cells in children is lower than in adults. It was proved that the DD genotype was significantly more common in the group of children without rheumatologic pathology (p=0.02). Conclusion: In 70.5% of patients with JIA, COVID-19 infection has a mild, subclinical course. The polymorphic variants of the ACE1 rs4646994 gene can`t be considered as informative markers for the prognosis of COVID-19 in children. The study was performed within the framework of the Horizon 2020 program under the contract No. RN/07-2023 of 25.12.2023 and is one of the first to assess the relationship between the severity of COVID-19 and the allelic polymorphism of the ACE1 gene in JIA in the Ukrainian population. The search for candidate genes that influence the course of COVID-19 in children with JIA is ongoing. REFERENCES: [1] Abouzeid H, Alkholy UM, Abdou MA, et al. Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with CAP: A case-control study. Pediatr Pulmonol. 2017;52(12):1592-1598. doi:10.1002/ppul.23886. [2] Keikha M, Karbalaei M. Global distribution of ACE1 (rs4646994) and ACE2 (rs2285666) polymorphisms associated with COVID-19: A systematic review and meta-analysis. Microb Pathog. 2022;172:105781. doi:10.1016/j.micpath.2022.105781. Acknowledgements: NIL. Disclosure of Interests: None declared.