Stroke Associated with SARS-CoV-2 Infection and its Pathogenesis: A Systematic Review

Abstract

Introduction: The change of stroke incidence during the COVID-19 pandemic period and the proposed mechanisms of the relationship between SARS-CoV-2 and stroke is reviewed. Methods: Web of Science, PMC/Medline, and Scopus databases were searched until July 2020 without time and language limitations. After quality assessment, 22 articles were included in this study. Results: Based on the results, it is impossible to conclude any definite relationship between the rising or decreasing stroke frequency or the shift in the ischemic and hemorrhagic ratio and SARS-CoV-2 infection. However, it appears that SARS-CoV-2 infection has some correlation with stroke. The supposed mechanisms for the SARS-CoV-2-related hemorrhagic stroke include 1) SARS-CoV-2-related vasculopathy with the endothelial damage of small vessels, 2) viral infection-induced platelet dysfunction or thrombocytopenia, and 3) activation of the proinflammatory cascade leading to coagulopathy. The helpful strategies are receiving therapeutic anticoagulation for high D-dimer or a known thrombus due to SARS-CoV-2 infection, as well as using extracorporeal membrane oxygenation (ECMO) in some patients. Furthermore, the possible mechanisms for the SARS-CoV-2-related ischemic stroke include 1) dysregulation of angiotensin-converting enzyme 2 (a key host cellular receptor for SARSCoV- 2)-related physiologic functions, 2) endothelial cell damages, 3) thrombo-inflammation, and 4) coagulopathy and coagulation abnormalities related to SARS-CoV-2 infection. Conclusion: A better understanding of the SARS-CoV-2 pathogenesis and its relation to neurologic abnormalities such as stroke can help to design new therapeutic approaches.