Potential mechanisms of hemorrhagic stroke in elderly COVID-19 patients

Abstract

The novel severe acute respiratory syndrome coronavirus 2 is the causative agent of coronavirus disease 2019, a new human infectious disease. While fever, cough, and respiratory distress are typical first symptoms, a fraction of those affected present instead with neurological symptoms suggestive of central nervous system compromise. This review summarizes the potential contribution of coronavirus disease 2019 to hemorrhagic stroke in the elderly and proposes possible mechanisms. Reports show that the most affected patients have underlying chronic diseases such as hypertension and diabetes, which are two key risk factors for hemorrhagic stroke. Angiotensin-converting enzyme 2 is the main host cell surface receptor interacting with the severe acute respiratory syndrome coronavirus 2 spike glycoprotein to allow viral entry and infection. We speculate that ensuing downregulation of angiotensin-converting enzyme 2 expression may compound the risk conferred by pre-existing comorbidities and critically influence the pathogenesis of hemorrhagic stroke by elevating blood pressure and impairing cerebrovascular endothelial function. Additionally, both age- and/or disease-related immune dysfunction and enhanced catecholamine release secondary to anxiety and stress may also aggravate central nervous system symptoms of severe acute respiratory syndrome coronavirus 2 infection. Thus, assessment of systemic inflammatory biomarkers and tight control of hemodynamic parameters upon admission are crucial to minimize mortality and morbidity in coronavirus disease 2019 patients with central nervous system symptoms suggestive of incipient stroke.

Keywords: ACE2; COVID-19; SARS-CoV-2; hemorrhagic stroke; immunity.

Figure 1

Potential mechanisms mediating increased risk of hemorrhagic stroke in COVID-19 patients. The RBD of SARS-CoV-2’ spike protein interacts with ACE2, leading to ACE2 downregulation. ACE2 deficiency impairs endothelial function in cerebral arteries and determines an increase in Ang-II levels, which elevates BP through activation of AT1 receptors (AT1R). Simultaneously, reduced ACE2 leads to a decrease in Ang (1-7) levels, weakening its vasculo-protective effects mediated by Mas receptor (MasR) activation.