INFLUENCE OF GENE POLYMORPHISM, SEVERITY OF CLINICAL COURSE OF THE DISEASE AND COMBINATION WITH COMORBIDITIES ON CELLULAR AND GENERAL REACTIVITY IN PATIENTS WITH COVID-19

Abstract

Background. In the pathogenesis of COVID-19 development, cellular and general reactivity of the patient's body in response to exo- and endo-intoxication are important indicators, they are diagnostic markers of the severity of the disease. Aim: to find out and analyze the effect of gene polymorphism, severity of the clinical course of the disease and combination with comorbidities on the cellular and general body reactivity of patients with COVID-19. Materials and methods. The study included 204 patients with mild, moderate, and severe COVID-19-associated pneumonia who had comorbidities: cardiovascular disease (82 patients), endocrinopathy (46 patients), and comorbidities of the ENT organs, connective tissue, gastrointestinal tract, chronic kidney disease (CKD), who were grouped into the group "other comorbidities (76 patients). Among the patients were 51.97% (106) women and 48.03% (98) men. The average age of patients was 55.93±8.75 years. The polymorphism of the TMPRSS2 (rs12329760), FGB (rs1800790) and NOS3 (rs2070744) genes was investigated by real-time polymerase chain reaction (Real Time PCR). The level of cellular and general reactivity of the body of patients with coronavirus infection was determined by the cellular resistance index and leukocyte indices of intoxication (LII) according to J.Y. Kalf-Kalf, Reis, Himich, modified leukocyte index, intoxication index, hematological index of intoxication according to V.S. Vasiliev and nuclear index of endotoxemia. Results. It was found that patients with coronavirus infection carry mutational T-alleles of the gene (especially TT genotype) of the TMPRSS2 gene (rs12329760), A-allele of the FGB gene (rs1800790) and T-allele of the NOS3 gene (rs2070744) have the highest level of cellular resistance and cellular reactivity in response to endo- and exo-intoxication, which leads to a probable decrease in intoxication and is an adaptive defense response of the body. It was found that in the mild clinical course of coronavirus infection, the highest level of cellular reactivity and cellular resistance is observed, in the moderate course, the cellular reactivity of the body decreases by 81.34%, and in the severe course - by 45.35%, while high to moderate endo- and exo-intoxication, respectively, persists. In comorbidity with endocrinopathies or cardiovascular diseases (CVD), lower cellular resistance (especially in CVD) was found than in the combination of COVID-19 with other comorbidities in the remission/compensation phase - by 32, 64% (p<0.001) and 38.60% (p<0.001) against the background of higher endogenous intoxication according to the modified intoxication index and Reiss LI - by 30.21-40.0% (p≤0.032-0.017), respectively. Conclusion. The severity of the clinical course, the presence of comorbidities, polymorphism of the genes TMPRSS2 (rs12329760), FGB (rs1800790), NOS3 (rs2070744) have a multidirectional effect on cellular and general reactivity in patients with COVID-19.