Coronavirus Disease 2019 and Stroke: Clinical Manifestations and Pathophysiological Insights

Afshin A Divani, Sasan Andalib, Mario Di Napoli, Simona Lattanzi, M Shazam Hussain, José Biller, Louise D McCullough, M Reza Azarpazhooh, Alina Seletska, Stephan A Mayer, Michel Torbey, Afshin A Divani, Sasan Andalib, Mario Di Napoli, Simona Lattanzi, M Shazam Hussain, José Biller, Louise D McCullough, M Reza Azarpazhooh, Alina Seletska, Stephan A Mayer, Michel Torbey

Abstract

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest that axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the clinical manifestations and pathophysiological mechanisms of stroke in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.

Keywords: ACE2; COVID-19; Endothelial damage; Pandemic; Renin-angiotensin system; SARS-CoV-2; Stroke.

Conflict of interest statement

Declaration of Competing Interest The authors declare no conflict of interest with regard to this paper.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
Schematic process of endocytosis of SARS-COV-2, proliferation of the virus inside the cell, and effect of virus upon RAS. Having been primed by TMPRSS2, SARS-COV-2’s spike glycoprotein binds to ACE2. The virus enters the cell and is proliferated. SARS-COV-2 downregulates ACE2, which in turn under-activates the RAS alternative axis (ACE2-Ang-(1-7)-Mas). Under-activation of the alternative axis gives rise to over-activation of the classical RAS axis (ACE-Ang II-AT1R). The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response can contribute to the pathophysiology of stroke during SARS-CoV-2 infection. Abbreviations: SARS-COV-2: severe acute respiratory syndrome coronavirus 2, RAS: renin-angiotensin system, ACE2: angiotensin-converting enzyme 2, TMPRSS2: Transmembrane protease, serine 2, Ang: angiotensin, Mas: Mas receptor, AT1R: angiotensin 1 receptor.
Fig. 2
Fig. 2
Non-contrast head CT showing posterior fossa ICH with acute obstructive hydrocephalus in a COVID-19 positive patient.

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