Predicting risks of prothrombotic readiness under COVID-19 using genetic testing

Abstract

COVID-19 poses a significant hazard as regards decompensation of underlying chronic diseases, specific damage to the cardiovascular system, and a high risk of negative health outcomes such as thrombotic events. The coronavirus infection pathogenesis is rather complicated and has not been studied yet; this is largely due to peculiar features of the virus and the initial state of homeostasis in a patient. In this study, our aim was to analyze molecular-genetic markers of homeostasis in patients with the new coronavirus infection COVID-19 as a prognostic trigger of developing pro-thrombotic readiness. Hospitalized patients with COVID-19 were chosen as study objects. We performed molecular-genetic analysis of basic genes significant for homeostasis including several factors such as V (rs6025), II (rs1799963), I (rs1800790), VII (rs6046), XIII A1 (rs5985)), IGN A2 (rs1126643), IGN B3 (rs5918), and PAI-1 (rs1799889). The thrombinemia severity was identified by thrombin generation tests using the Ceveron®alpha automated coagulation analyzer with TGA-module. Allelic variants of PAI-1, prothrombin (FII), and fibrinogen (FI) determined high thrombinemia as per the thrombin kinetics test (endogenous thrombin potential (AUC), peak thrombin concentration (peak-thrombin), time necessary to reach thrombin peak (tPeak), levels of fibrinogen and D-dimer) in COVID-19 patients during the entire hospitalization. We established that elevated thrombin generation becoming apparent through elevated levels of endogenous thrombin potential (AUC) might be a prognostic indicator of the pro-thrombotic state in patients with genetic polymorphisms of PAI-I and fibrinogen. The study results indicate that pro-thrombotic readiness is determined genetically in case COVID-19 patients have allelic variants in PAI-I, prothrombin (factor II) and fibrinogen (factor I) genes.