The potential role of microvascular pathology in the neurological manifestations of coronavirus infection

Abstract

Human coronaviruses are highly pathogenic viruses that pose a serious threat to human health. Examples include the severe acute respiratory syndrome outbreak of 2003 (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) outbreak of 2012, and the current SARS-CoV-2 (COVID-19) pandemic. Herein, we review the neurological manifestations of coronaviruses and discuss the potential pathogenic role of blood–brain barrier dysfunction. We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood of neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood–brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavirus neuropathology, and to test the diagnostic potential of minimally-invasive screening tools (e.g. serum biomarkers, fluorescein retinal angiography and dynamic-contrast MRI).

SARS-CoV-2 Poorly Replicates in Cells of the Human Blood-Brain Barrier Without Associated Deleterious Effects

“…Moreover it was recently described that the virus can directly infect neurons and can be found in the brain or in the CSF of COVID-19 patients (15)(16)(17)(18). In addition, numerous pathologies affecting neurovasculature have been reported in patients, such as thromboembolism or ischemic stroke, highlighting a potential role of the BBB in the neurological COVID-19 diseases (60,61). Despite these observations, the mechanisms of SARS-CoV-2 access to the brain are poorly described.…”

Brain Barriers and brain fluids research in 2020 and the fluids and barriers of the CNS thematic series on advances in in vitro modeling of the blood–brain barrier and neurovascular unit

“…Another possibility is that SARS-CoV-2 may directly affect cells of the NVU and lead to neurological dysfunction [87]. In vitro, Buzhdygan et al [88] found that the spike protein of SARS-CoV-2 induced a loss of brain endothelial cell barrier integrity and triggered a proinflammatory response.…”

Neuropsychiatric manifestations of COVID-19, potential neurotropic mechanisms, and therapeutic interventions

“…Many factors, including frailty, comorbidities (e.g., hypertension, diabetes, cardiovascular disease, and chronic respiratory disease), and compromised immune function may contribute to worse health outcomes and a high mortality rate. Cardiovascular disease, diabetes, hypertension, or other comorbidities, preexisting microvascular pathology may further facilitate the neuroinvasion of the coronavirus and contribute to the development of neuropsychiatric symptoms and neuropathology associated with the viral infection [ 5 ]. The presence of chronic neurological comorbidity is an independent predictor of all-cause mortality in hospitalized COVID-19 patients [ 6 ].…”