SARS-CoV-2: is there neuroinvasion?

Abstract

Background SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF. Main body We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways. Conclusions While SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.

Stellate ganglion block reduces symptoms of Long COVID: A case series

“…Whether or not SARS-CoV-2 is neuroinvasive is an open question ( McQuaid et al, 2021 ). Although it can infect human brain organoids ( Song et al, 2021 ), neuroinvasion appears uncommon except in severe COVID-19.…”

Does SARS-CoV-2 affect neurodegenerative disorders? TLR2, a potential receptor for SARS-CoV-2 in the CNS

“…Armocida and colleagues proposed that the virus could infect neurons in the peripheral nervous system and then take advantage of axonal transport to gain access to the CNS 47 . McQuaid et al suggested the lateral ventricles and choroid plexus as a CNS entry mechanism for SARS-CoV-2 48 . Since these regions contain epithelial cells, which express ACE2, it has been suggested that the virus could cross the blood-cerebrospinal fluid barrier and enter the choroid plexus and ventricular system.…”

Neuroinflammation and Its Impact on the Pathogenesis of COVID-19

“…Alteration of BBB integrity during infection may facilitate the entry of the SARS-CoV2 virus into the CNS, where it can then bind to ACE2 receptors of glial cells or neurons ( 142 , 159 ). However, even though SARS-CoV-2 has been detected in brains of severe COVID-19 cases, the entry mechanism(s) remains unclear ( 165 ). It has been proposed that SARS-CoV-2 may infect the brain directly via axonal transport mediated by the olfactory nerve ( 166 ).…”

“…It has been proposed that SARS-CoV-2 may infect the brain directly via axonal transport mediated by the olfactory nerve ( 166 ). Other possibilities for the virus entry into the brain include trafficking through the BBB using leukocytes as carriers or viral neuroinvasion through the GI tract ( 165 , 167 , 168 ).…”