NONSPECIFIC ANTIINFECTIVE PROTECTION IN PATIENTS WITH COVID-19 DEPENDING ON GENE POLYMORPHISM, DISEASE SEVERITY AND COMORBIDITY

Background. The level of antiinfective protection is important in the comprehensive assessment of the immune status of patients, the study of which will provide an opportunity to develop a high-quality set of therapeutic and preventive measures to improve the effectiveness of medical care for patients with COVID-19. Aim: to conduct a comprehensive analysis of the level of nonspecific antiinfective protection in patients with COVID-19 depending on the polymorphism of the genes TMPRSS2 (C-allele; rs12329760), FGB (G-allele; rs1800790) and eNOS (T-allele; rs2070744), the severity of the disease and the combination with comorbidities. Materials and methods. We examined 204 patients with coronavirus infection who were hospitalized in the Infectious Diseases Department of the Uman Central City Hospital during 2021-2023, among the patients there were 51.97% (106) women, 48.03% (98) men, the average age of patients was 55.93±8.75 years. Comorbidity was retrospectively established in patients participating in the cohort study: 82 patients had concomitant cardiovascular disease; 46 patients were diagnosed with endocrine pathology; 76 patients had other comorbidities, which were grouped into one group “Other comorbidities”. The polymorphism of the TMPRSS2 (rs12329760), FGB (rs1800790) and NOS3 (rs2070744) genes was investigated by real-time polymerase chain reaction (Real Time PCR) in 96 patients. The level of nonspecific antiinfective protection of patients was determined by the following indicators: neutrophil granulocyte response, neutrophil-lymphocyte ratio, neutrophil shift index, neutrophil-monocyte ratio, etc. Results. It has been established that the reactive response of neutrophil granulocytes (NG) is higher in patients with COVID-19 who carry the wild G-allele (especially the GG genotype) of the FGB gene (rs1800790) - by 60, 0% (p=0.007), TT-genotype of the TMPRSS2 gene (rs12329760) - by 41.38% (p=0.012) and wild T-allele of the NOS3 gene (rs2070744) - by 29.87% (p=0.046). Severe and, to a lesser extent, moderate COVID-19 is accompanied by a lower level of cellular nonspecific resistance - by 34.33% (p<0.001), nonspecific reactivity and reactive response - by 45, 34% (p=0.002) and 15.02%, with a worse response to endo- and exo-intoxication in coronavirus infection with lower leukocyte intoxication indices (LII) by 29.56-41.50% (p≤0.049-0.003). Comorbidities significantly worsen the clinical and laboratory course of COVID-19: the lowest cellular reactivity with the highest reactive response of NG was found in comorbidity with cardiovascular disease against the background of more severe endogenous intoxication - by 38.60% (p<0.001) and 30.21-40.0% (p≤0.032-0.017), respectively. Conclusion. Polymorphism of FGB (rs1800790), TMPRSS2 (rs12329760), NOS3 (rs2070744) genes, disease severity and comorbidities have different effects on nonspecific antiinfective protection in patients with COVID-19.