Genetic Predisposition to a Vascular Catastrophe: Does It Affect Severe COVID-19?

ABSTRACT

Introduction. Targeted at the hemostatic system and the vascular endothelium, COVID-19 triggers the pathogenetic cascade of disorders in these systems. This cascade leads to the cerebral infarction, significant aggravation of other neurovas-cular diseases and neurological disorders, which requires an in-depth study. Objective: to identify the impact of factors selected among 21 candidate genes and metabolic markers on disease severity and the probability of death from SARS-CoV-2 infection in patients with a history of ischemic stroke (IS) and apparently healthy participants. Materials and Methods. We analyzed genetic, clinical, and laboratory findings in 85 patients with IS occurred at least one year before the study. During the first stage, participants were divided into three groups Group 1 — 25 patients with a history of IS and COVID-19 at least one year prior to the study;Group 2 — 35 patients with IS history and no clinical manifestations or known COVID-19 history at baseline;and Group 3 — 20 apparently healthy participants as controls who had no clinical manifestations or information about a positive test for COVID-19 at baseline (November 2021). During the second stage, a new Group 4 included 25 patients with a history of IS who were treated for COVID-19 at baseline. Single venous blood tests were used to assess the levels of metabolic markers and identify genetic polymorphisms of hemostasis, immune response, endothelial function, and lipid metabolism in all study participants. Results. We identified the significant factors that determined the irreversible effects (damage) and fatal outcomes in patients with COVID-19 via the throm-bophilia genetic polymorphisms variations as follows F13 encoding fibrin-stabilizing factor XIII — fibrinase (statistical probability of the factor influence > 90%), and SERPINE1 encoding endothelial plasminogen activator inhibitor-1 (PAI-1;statistical probability of the factor influence > 95%). High admission levels of homocysteine, interleukin-6, and activated partial thromboplastin time in patients with COVID-19 were associated with a severe disease course and fatal outcomes. Conclusion. Information about gene variations that trigger thrombosis and the adequate immune response can improve the effectiveness of specific therapy. Patients should understand their genetic profile, since this knowledge may prevent COVID-19 complications and significantly reduce the risk of a vascular catastrophe. © Dutova T. I., Banin I. N., Sazonov I. E., Peleshenko E. I., 2023.