Update on cerebrovascular manifestations of COVID-19

Abstract

The novel member of coronaviruses family, severe acute respiratory coronavirus-2 (SARS-CoV-2), with high structural homology to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS) has spread rapidly with about 20 million cases infection and over 700,000 deaths. SARS-CoV-2 has been emerged as a worldwide disaster due to non-specific few respiratory and gastrointestinal manifestations at the onset of disease as well as long incubation period. Surprisingly, not only respiratory failure but also the underlying coagulation disorder and neurovascular involvement worsen the clinical outcome of infected patients. In this review article, we describe the probable mechanisms of SARS-CoV-2 infection and stroke occurrence. We will also discuss the cerebrovascular events following SARS-CoV-2 infection, the recommended therapies, and future prospects to better manage these patients in coronavirus disease 2019 (COVID-19) outbreak.

Keywords: Anticoagulative therapies; COVID-19; Coagulation; Coronavirus; SARS-CoV-2; Stroke.

Fig. 1

Lung alveolus in phases I and II. SARS-CoV-2 enters into type II alveolar epithelial cells via TMPRSS2 or ACE2 receptors. After viral replication and proliferation, immune response is initiated by monocytes, macrophages, and neutrophils. Then at phase III, inflammatory cytokines such as IL-2, 6, 7, TNF-α, and IFN-γ induce the cytokine storm and systemic inflammation. Lung parenchymal injury is occurred following inflammatory processes, vasodilation, endothelial permeability, leukocyte recruitment, and pulmonary edema. Lung vascular endothelium destruction by direct SARS-CoV-2 entrance and induced inflammation can predispose microthrombus formation and lung infarction

Fig. 2

SARS-CoV-2 directly induces the endothelial cell death in the blood-brain barrier (BBB). The tight junctions in endothelial cells are destructed through monocytes, neutrophils, IL-1β, and TNF-α. In addition to underlying coagulopathy, the basement membrane and Von-Willebrand factor (VWF) contiguity with platelets and RBCs facilitate thrombus formation. The developed thrombus in the brain or other origins such as cardiac thrombus or deep vein thrombus can potentially embolize to distal parts or other branches. Hypoxia-induced vasodilation besides endothelial damage makes the possibility of SARS-CoV-2 dissemination to brain parenchyma or cerebrospinal fluid. High thrombin level due to low protein C, antithrombin III, and tissue factor pathway inhibitor amplifies the function of proteinase-activated inhibitor 1 (PAR-1) receptors which is led to inflammation. AT-III, antithrombin III; Pro C, protein c; TFI, tissue factor pathway inhibitor