[18]
The neuro-targeting nature of the virus can explain the correlation of SARS-COV-2 severity and the ischemic stroke due to the vascular injury and the hyperimmune response. These responses alter the blood-brain barrier permitting the virus to bind to the ACE2 receptor in the glial cells, which, in addition to the hypercoagulation, plays an important role in the development of ischemic stroke. [11,15].
Although the underlying pathophysiological process responsible for the development of stroke in COVID-19 has not yet been determined, different mechanisms related to the COVID-19 infectious process were postulated, such as the host’s hyperinflammatory response with the exaggerated cytokine release. For instance, interleukins play an essential role in the inflammatory response, and COVID-19 patients; IL-1, a macrophage-secreted interleukin, is elevated, especially in severe COVID-19 cases. [4] Other inflammatory mediators responsible for activating acute-phase reactions like interferon-gamma[5] , tumor necrosis factor-alpha, and IL-6 were also elevated in SARS-COV-2 infected patients [8,9] . IL-6 activity has a unique importance as it’s considered a target for tocilizumab, an IL-6 receptor antagonist with possible alleviation of the SARS-COV2-associated cytokines storm and subsequently the severity of the infection.[20].
Jenny et al. has addressed the relationship between the Inflammatory cytokines and risk for ischemic stroke risk in their cohort study. They found that raised IL-6 levels were associated with increased risk of ischemic stroke (mean 4.5 vs. 3.7ng/mL; p < 0.001)[14]. Another factor supporting this association is the endothelial injury, as described by Varga et al., where the histopathology of different samples from three patients with SARS-COV2 infection confirmed evidence of viral endothelial invasion with subsequent accumulation of the inflammatory cells attributed to the widespread of ACE2 receptors through the endothelial vascular lining