Genetic predictors of survival and development of MACE in the acute COVID-19 in patients with high cardiovascular risk
Authors:   S.M. Kirov Military Medical Academy, Tyuryupov M.S. ,   St. Petersburg, Russian Federation, Shulenin K.S. ,   S.M. Kirov Military Medical Academy; St. Petersburg, Russian Federation, Svyoklina T.S. ,   S.M. Kirov Military Medical Academy; St. Petersburg, Russian Federation, Kutelev G.G. ,   S.M. Kirov Military Medical Academy; St. Petersburg, Russian Federation, Shulenin D.K. ,   S.M. Kirov Military Medical Academy; St. Petersburg, Russian Federation, Alanichev A.E. ,   S.M. Kirov Military Medical Academy; St. Petersburg, Russian Federation, Cherkashin D.V. ,   S.M. Kirov Military Medical Academy; St. Petersburg, Russian Federation
Published: May 2024

Introduction. Despite the fact that the SARS-CoV-2 virus is highly contagious, the clinical manifestations of the disease caused by it can have significant differences: from a low-symptom course to extremely severe forms with the development of a fatal outcome. It is obvious that the observed polymorphism of the development of infection caused by SARS-CoV-2 is due, among other things, to genetic factors. These include single-nucleotide polymorphisms of genes involved in the stages of the pathogenesis of infection: from the penetration of the virus into target cells, the expression of its RNA to the response of the host organism. The study of genetic predictors that cause changes in susceptibility to the SARS-CoV-2 virus and differences in the severity of infection will help to better understand the pathogenesis of this disease and give an idea of promising areas of therapy and prevention. Aim. To study the relationship of genetic biomarkers with the severity of infection caused by SARS-CoV-2, cardiovascular complications and the risk of death in the early period of the disease. Design. A single-center retrospective study. Materials and methods. The study included 164 patients (90 men, 74 women) with infection caused by SARS-CoV-2. All patients were classified as high and very high cardiovascular risk. Concomitant somatic pathology: arterial hypertension in 164 (100%), coronary heart disease in 80 (48.9%), alimentary obesity in 100 (61%), prediabetes in 52 (31.74%), chronic kidney disease in 34 (20.7%) patients. At the first stage of the study, the relationship of genetic biomarkers with the severity of the disease was evaluated, at the second — with cardiovascular complications, and at the third — with the onset of death. Results. In the group of patients with severe disease, variant DD of ACE Alu I/D gene polymorphism, rs4646994 (p = 0.004), variant GG of IL-10 polymorphism 1082 G/A, rs1800896 (p = 0.043), allele *11 HLA-DRB1 (p = 0.015) were significantly more common. The genetic predictors of the development of cardiovascular complications were the genotype DD of the ACE gene (rs4646994) (p = 0.038), the allele *3 HLA-DRB1 (p = 0.041), the allele *13 HLA-DRB1 (p = 0.047) was less common. When searching for a correlation between the selected genetic biomarkers and mortality, only a negative contribution of the ACE Alu I/D polymorphism variant DD, rs4646994 (p = 0.015) was revealed. The survival analysis showed that in the DD variant of the ACE Alu polymorphism I/D, rs4646994, the median survival rate is lower than in the II variant (13 (9–15) days and 21 (12–n/o) days, respectively (p = 0.03)), and lower than in the ID (31 variant (14–n/ o) day (p < 0.0001)). The survival rate of patients with the heterozygous variant of the polymorphism MTRR –66 A/G, rs1801394 was 11.5 (9–16) days, with variant AA — 7 (3–n/o), and with variant GG — 6 (4–14), p = 0.013. With the *16 HLA DRB1 allele, survival was only 5.5 (2–n/o) days versus 22 (17–n/o) days in patients without it, p = 0.04. Conclusion. Predictors of an increased risk of severe infection caused by SARS-CoV-2 include the DD variant of the ACE Alu I/D gene polymorphism, rs4646994, the GG variant of the IL-10 1082 G/A gene polymorphism, rs1800896 and the *11 HLA-DRB1 allele. The negative effect of the DD variant of the polymorphism of the ACE Alu I/D gene, rs4646994, the *3 HLA-DRB1 allele and the protective effect of the *13 HLA-DRB1 allele have been proven in relation to the overall risk of major cardiovascular complications. The carriage of the *16 HLA-DRB1 allele and the DD variant of the ACE Alu I/D gene polymorphism, rs4646994, correlate with an increased risk of early hospital mortality in patients. At the same time, the heterozygous variant of the MTRR –66 A/G polymorphism, rs1801394, is a protective biomarker and is associated with better survival. Key words: COVID-19, SARS-CoV-2 virus, mortality, cardiovascular complications, cardiovascular risk, genetic biomarkers