Molecular and genetic aspects of the pathogenesis of COVID-associated thrombosis

Abstract

Annotation. COVID-19 is a viral infectious disease that reached pandemic proportions in 2020. The SARS-CoV-2 virus, which is the etiological factor of the coronavirus disease, has a complex mechanism of impact on the human body, causing various manifestations and causing complications of the disease. As you know, a severe form of coronavirus infection is associated with dire consequences, among which the main step is a violation of the coagulation system, which has the appearance of CVD syndrome, but its main symptom is thrombosis of arterial and venous vessels. The frequency of occurrence of thrombocytopenia forces us to investigate the pathogenesis of the development of this process to reduce the number of cases. However, there is still no clear opinion about the pathogenesis of such thrombosis. Therefore, the purpose of this review was to analyse the most probable mechanisms of development of venous and/or arterial thrombosis associated with coronavirus disease. In the course of the study, 64 information sources were analysed, extracted from PubMed, Web of Science, Google Scholar, and Elsevier databases. At the beginning of a thorough analysis of information, the following main links of COVID-associated thrombosis were identified: direct hyperactivation of blood platelets, which leads, through the participation of their surface molecules (P-selectin, CD40L, etc.), to the activation of aggregation and adhesion of platelets; ACE2 - mediated cell activation and endothelial dysfunction, which together have the property of stimulating thrombus formation; activation of the NETosis process, the MAPK pathway, Toll-like receptors and the Nox2 enzyme system, which also through a cascade of various reactions, which are described below, cause thrombosis. We understood that these several pathogenetic chains can work relatively separately, but the difficulty in describing the development of thrombotic disease caused by the SARS-CoV-2 virus is that these aspects of pathogenesis are closely related and intertwined at different links, forming both direct and feedback loops, and vicious circles. The obtained structured data can serve as a basis for further original research, which will allow the development of targeted therapy for the treatment and prevention of post-covid thromboses, directed at the described molecular genetic aspects.