Role of polymorphisms of genes involved in hemostasis in COVID-19 pathogenesis

Abstract

Objective. To analyze polymorphisms of genes involved in hemostasis among patients with coronavirus disease 2019 (COVID 19) to improve the diagnosis of coagulopathy and prognosis of COVID-19 severity. Patients and methods. We have examined 52 patients with COVID-19 aged 33 to 84 years. Of them, 30 individuals (Group 1) were hospitalized with extremely severe (1A) and severe (1B) disease, whereas 22 patients with mild and asymptomatic disease were treated in outpatient departments (group 2). We assessed allelic variants of genes associated with hemostasis dysfunction (including FGB, FII, FV, FVII, F13A1, PAI-I, Gp1a, and Gp3a) using genomic DNA isolated from peripheral blood leukocytes. Polymorphisms were detected by polymerase chain reaction. Data analysis was performed using the Statistica, version 12 (StatSoft, USA). To compare independent categorical variables, we constructed contingency tables, performed Pearson chisquare test with Yates correction, Fisher exact test, and calculated relative risk (RR) [CI]. Results. COVID-induced coagulopathy (CAC) was diagnosed in 16.7% of patients; risk of CAC was identified in 30% of patients; sepsis-induced coagulopathy (SIC) was observed in 3.3% of patients; none of study participants had disseminated intravascular coagulation (DIC). Hemostasis impairments were more common in group 1A (RR = 2.28 [1.16–4.48]). Only patients from Group 1 had mutations in the gene encoding prothrombin (FII) –6.9% (RR = 1.78 [1.40–2.28]); protective polymorphisms in the FVII gene were more common in patients from Group 2 (χ2 = 3.28, р = 0.046); the rs 5985 polymorphism in the F13A1 gene was more common in patients from Group 1 (RR = 1.73 [1.06–2.82]). Patients with extremely severe COVID- 19 were more likely to have polymorphisms in the Gp1a gene (ITGA2) (RR =1.64 [1.05–2.56]) and F13A1 gene (χ2 = 2.67, р = 0.05), as well as homozygous mutation in the FII gene; they had no polymorphisms in the FVII gene (10976G→A). Thrombophilia, detected in 3 patients from Group 1, was a risk factor for thrombocytopenia (RR = 13.5 [3.56–51.23]), САС (RR = 9.0 [3.1–26.16]), and death (n = 4). The 4G allele (4G/4G, 4G/5G variants) in the PAI-I gene (rs 1799889), causing impaired fibrinolysis, was more frequently registered in patients with mild COVID-19 (91%) than in those with extremely severe COVID-19 (70%). It is possible that patients with extremely severe disease develop transient hyperfibrinolysis, which results in the transformation of local pulmonary COVID-19 into sepsis. Therefore, the 4G/4G and 4G/5G polymorphisms may have a protective role. Key words: hemostasis, COVID-19, polymorphism, genetics, COVID-induced coagulopathy