Ischemic stroke, inflammation, and endotheliopathy in COVID-19 patients

Objective: Early reports suggest an increased risk of ischemic stroke during COVID-19 infection. We aimed to identify patients with COVID-19 and ischemic stroke and explore markers of endotheliopathy, inflammation, and hypercoagulability. Background: Novel coronavirus-19 disease (COVID-19) is associated with a diverse array of neurologic complications, including ischemic stroke. Suspected mechanisms include hypercoagulability and endothelial injury, although evidence is sparse in stroke patients. Design/Methods: This was a retrospective, observational cohort study of patients with acute ischemic stroke and COVID-19 (n=21) compared to non-COVID-19 acute ischemic stroke patients (n=11). Timing of stroke onset during COVID-19 course, acute phase reactant levels, cytokine levels, endothelial activation, and hypercoagulability were evaluated with respect to stroke onset and etiology. Results: Twenty-one ischemic stroke patients were diagnosed with COVID-19 during the study period. Both groups had a similar age and burden of vascular risk factors. COVID-19 patients had significantly higher levels of endothelial activation around the time of stroke when compared to controls. The mean Factor VIII level was 332% of normal in the COVID-19 group and 49% in the control group, while von Willebrand Factor antigen and activity were 330% and 285% in the COVID-19 group and 213% and 152% in the control group, respectively. Cytokine storming and a strong inflammatory responses are defining features of severe COVID-19. We demonstrated a temporal correlation between stroke onset and the peak of acute phase reactants. Elevated cytokine levels, IL-6 and soluble IL-2 receptor levels in particular, were significantly associated with embolic stroke of undetermined source (ESUS) in COVID-19 patients when compared with other etiologies. Conclusions: We provide emerging evidence that endotheliopathy and the systemic inflammatory response in patients with vascular risk factors and COVID-19 is associated with ischemic stroke. Further research is needed. Understanding the mechanism of stroke in COVID- 19 patients will be critical in providing primary stroke prevention and treatment.