Cerebral Vasomotor Reactivity in COVID-19: A Narrative Review【MDPI Open Access Journals 2023年7月24日】


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily affects the respiratory system but can also lead to neurological complications. Among COVID-19 patients, the endothelium is considered the Achilles heel. A variety of endothelial dysfunctions may result from SARS-CoV-2 infection and subsequent endotheliitis, such as altered vascular tone, oxidative stress, and cytokine storms. The cerebral hemodynamic impairment that is caused is associated with a higher probability of severe disease and poor outcomes in patients with COVID-19. This review summarizes the most relevant literature on the role of vasomotor reactivity (VMR) in COVID-19 patients. An overview of the research articles is presented. Most of the studies have supported the hypothesis that endothelial dysfunction and cerebral VMR impairment occur in COVID-19 patients. Researchers believe these alterations may be due to direct viral invasion of the brain or indirect effects, such as inflammation and cytokines. Recently, researchers have concluded that viruses such as the Human Herpes Virus 8 and the Hantavirus predominantly affect endothelial cells and, therefore, affect cerebral hemodynamics. Especially in COVID-19 patients, impaired VMR is associated with a higher risk of severe disease and poor outcomes. Using VMR, one can gain valuable insight into a patient’s disease progression and make more informed decisions regarding appropriate treatment options. A new pandemic may develop with the COVID-19 virus or other viruses, making it essential that healthcare providers and researchers remain focused on developing new strategies for improving survival in such patients, particularly those with cerebrovascular risk factors.

1. Introduction

COVID-19 has become one of the leading causes of death worldwide, making it one of the most devastating health issues of the past few decades. Despite the primary target of COVID-19 being the respiratory system, mounting evidence indicates that it may also negatively impact the cerebrovascular system. In addition to respiratory symptoms, reports of neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are emerging. These neurological manifestations include headache, ageusia (loss of taste), anosmia (loss of smell), as well as severe complications including seizures, ischemic stroke, cerebral hemorrhage, encephalitis, and meningitis. Patients who suffer from severe clinical manifestations of SARS-CoV-2 infection are more likely to experience neurological symptoms compared to those who suffer from mild symptoms. This virus is distinguished by the presence of the spike (S) glycoprotein, which provides the virus with access to neural, glial, and endothelial cells containing angiotensin-converting enzyme 2 (ACE2). There is still much to be discovered about the pathophysiology of this virus and how it affects the nervous system. However, it is believed that the neurological manifestations of acute COVID-19 can be attributed to multiple overlapping pathogenetic mechanisms. These include viral neuroinvasion, endotheliopathy associated with blood–brain barrier dysfunction, coagulopathies that precipitate hypoxic-ischemic neuronal damage, metabolic imbalances, oxidative stress cascades, and cellular apoptosis.

In COVID-19 patients, the endothelial cells are regarded as the Achilles heel since injury to the endothelium will initiate and propagate SARS-CoV-2 infection. The endothelium produces substances that cause blood vessels to contract or relax, which corresponds to cerebral hemodynamic vasomotor reactivity (VMR). With vasodilator stimulation, such as CO2 inhalation, breath-holding test (BHT), or acetazolamide administration, VMR can be assessed using rates of blood flow in cerebral arteries and changes in blood flow caused by hypercarbia. The impairment of vasoreactivity and reduced reserve capacity in brain arteries predispose patients to cerebrovascular disease. Recently, researchers have found that impaired VMR is associated with a higher probability of severe illness and poor outcomes in patients with COVID-19. It is worth mentioning that structural changes in vasculature occur more slowly than functional changes. Hence, functional assessment of the vasculature, such as the VMR assessment, is more sensitive than structural analysis when acute exposure to the disease process is present. Researchers have shown that viruses other than SARS-CoV-2, such as the Human Herpesvirus 8 and Hantavirus, can negatively impact cerebral hemodynamics. In treating patients with viral infections such as COVID-19, physicians should consider VMR because of its potential to implement an appropriate, speedy, and aggressive treatment to improve neurological sequelae. Additionally, VMR has been observed to change over time in patients with different clinical neurologic manifestations, suggesting it could be a biomarker for the disease’s progression. It may be possible to prescribe targeted interventions to patients who might benefit from them, resulting in improved patient outcomes. Furthermore, it would reduce the burden associated with cerebrovascular disorders by utilizing valuable information obtained from a VMR evaluation.

This review summarizes the most relevant literature on cerebral hemodynamic changes, particularly VMR impairment in COVID-19 patients in the acute or chronic infection phases.