Alterations in the fibrinolysis system and plasma cytokine profile following COVID-19 in patients with chronic cerebral ischemia

This review examines the pathogenetic mechanisms of nervous system damage in patients with chronic cerebral ischemia and COVID-19. It is believed that in cases of coronavirus disease, nervous system damage can occur due to various reasons: direct viral invasion, excessive activation of the immune response (cytokine storm), and the development of systemic hypoxemia. The affinity of SARS-CoV-2 for ACE2 receptors also leads to direct damage to intracranial arteries. These processes are accompanied by changes in blood coagulation/anticoagulation systems, significantly impacting the pathogenesis of both diseases. Due to the activation of pro-inflammatory cytokines and endothelial dysfunction, there is increased permeability of the blood-brain barrier (BBB), leading to the migration of T-lymphocytes and inflammatory mediators into the interstitial space of the brain. The immune-mediated inflammatory reaction leads to the formation of subcortical demyelination and the activation of astrocytes. Fibrinogen, transforming into fibrin, enters the central nervous system, activating local inflammation processes, blocking the maturation of oligodendrocytes, disrupting myelinogenesis, and promoting the formation of beta-amyloid plaques. The existing state of hypercoagulation increases the risk of developing ischemic foci in the brain in patients with COVID-19. Simultaneously, the activation of the fibrinolysis system occurs, with increased levels of type 1 tissue plasminogen activator (PAI-1), a key marker of endothelial dysfunction, and a factor regulating fibrinolysis.Targeted inhibition of PAI-1 may hold promise as a new therapeutic strategy to improve treatment outcomes and prevent complications from the nervous system.