Аннотация:Background. Coronavirus disease 2019 (COVID-19) is a highly contagious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several risk factors of COVID-19 susceptibility and severity are associated with oxidative stress.Aim: to investigate the association of single nucleotide polymorphisms (SNPs) of glutathione S-transferase pi-1 (GSTP1) and glutathione peroxidase 4 (GPX4) genes with the severity of COVID-19.Methods. Study subjects were divided into two groups based on the severity of their symptoms. Allele-specific real time polymerase chain reaction (RT-PCR) was used for genotyping, and multifactor dimensionality reduction (MDR) analysis was performed to investigate the SNP-SNP interaction models.Results. The results showed a significant association of GPX4 rs713041 with the severity of COVID-19 (p=0.035). Most of GPX4 718TT carriers had a severe course of COVID-19 (OR=3.50; 95% CI [1.18-10.35]). The resulted three-locus SNP-SNP interaction model was statistically significant (p=0.0084, OR = 2.42; 95% CI [1.24 - 4.73]). Linkage disequilibrium analysis of GSTP1 SNPs rs1695 and rs1138272 showed a high possibility of linkage disequilibrium between the two sites (D’ = 0.949).Conclusions: To our knowledge, this is the first study to investigate the association of GSTP1 rs1695, GSTP1 rs1138272, and GPX4 rs713041 and SNP-SNP interaction with the severity of COVID-19 symptoms. The obtained results may serve as a novel potential factor of COVID-19 prognosis.