Case-control Study of the Association between Genetic Variants of Hemostasis System Genes and the Development of Venous Thrombosisin Patients Who Have Had COVID-19

Introduction: The coronavirus infection, COVID-19, still poses the most complex problem in medical science. One of the main links in the etiopathogenesis of this infection is the disturbance in the hemostasis system and capillary blood flow. The tendency to form blood clots in COVID-19 may be associated with a certain hereditary predisposition. Thus, the aim of this work is to study the correlation of several genetic variants with the hereditary predisposition to developing thrombosis following a new coronavirus infection of mild to moderate severity. Methods: This study was carried out on 182 patients aged 21 to 52 years who had episodes of venous thrombosis of various localizations within a year after clinically expressed COVID-19 of mild to moderate severity, confirmed by molecular genetic diagnostics of SARS-CoV-2. There were 154 patients in the control group aged 20 to 55 years (98 men and 58 women) who did not have such episodes after a mild or moderate infection (according to duplex analysis of vessels to exclude subclinical thrombosis and normal level D-dimer). The analysis of genetic variants of the hemostasis system genes (F2 c.20210G>A, F5 c.1691G>A, F7 c.10976G>A, F13 c.G>T, FGB c.-455 G>A, ITGA2 c.807C>T, ITGB3 c.1565 T>C, PAI c.-675 5G>4G) was performed using real-time PCR with automatic melting curve analysis. Statistical analysis of the results was performed using the chisquare analysis method on four-field genotype distribution tables, with a significance criterion of p =0.05 and the calculation of OR and CI. In some cases, Fisher's exact test was used. Results: The study showed a strong association between the development of thrombosis after a previous coronavirus infection and four polymorphic variants: F2 c.20210G>A (genotype GA + AA, OR = 4.75 (CI: 1.72 - 14.23, p <0.001)), F5 c.1691G>A (genotype GA + AA, OR = 5.92 (CI: 2.48 - 15.36, p <0.001)), ITGA2 c.807C>T (TT OR = 5.32 (CI: 2.86-6.09, p <0.0087)), and ITGB3 c.1565 T>C (genotype CC OR = 5.91 (CI: 2.6 - 13.31, p <0.001)). Conclusion: As a result, we identified a relationship between 4 polymorphic variants with a high risk of developing thrombophilia in patients who had a new coronavirus infection of mild to moderate severity.