How Does SARS-CoV-2 Effect the Central Nervous System?

As researchers across the globe have focused their attention on understanding SARS-CoV-2, the picture that is emerging is that of a coronavirus that has serious effects on the vasculature in multiple organ systems, including the cerebral vasculature, reported a study published by PubMed.gov.
Observed effects on the central nervous system include neurological symptoms (headache, nausea, dizziness), fatal microclot formation, and in rare cases, encephalitis.
However, our understanding of how the virus causes these mild to severe neurological symptoms and how the cerebral vasculature is impacted remains unclear.
Thus, the results presented in this report explored whether deleterious outcomes from the SARS-CoV-2 viral spike protein on primary human brain microvascular endothelial cells (hBMVECs) could be observed.
The spike protein, which plays a key role in receptor recognition, is formed by the S1 subunit containing a receptor-binding domain (RBD) and the S2 subunit.
First, using postmortem brain tissue, we show that the angiotensin-converting enzyme 2 or ACE2 (a known binding target for the SARS-CoV-2 spike protein) is ubiquitously expressed throughout various vessels calibers in the frontal cortex. Moreover, ACE2 expression was upregulated in cases of hypertension and dementia. ACE2 was also detectable in primary hBMVECs maintained under cell culture conditions.
Analysis of cell viability revealed that neither the S1, S2, or a truncated form of the S1 containing only the RBD had minimal effects on hBMVEC viability within a 48-hour exposure window.
The introduction of spike proteins to in-vitro models of the blood-brain barrier (BBB) showed significant changes to barrier properties.
Key to our findings is the demonstration that S1 promotes loss of barrier integrity in an advanced 3D microfluidic model of the human BBB, a platform that more closely resembles the physiological conditions at this CNS interface.
Evidence suggests that the SARS-CoV-2 spike proteins trigger a pro-inflammatory response on brain endothelial cells that may contribute to an altered state of BBB function.
'Together, these results are the first to show the direct impact that the SARS-CoV-2 spike protein could have on brain endothelial cells; thereby offering a plausible explanation for the neurological consequences seen in COVID-19 patients, concluded this study abstract.'
A further discussion was summarized in this attachment:
'To our knowledge, this is the first reported evaluation that examined the effects of the SARS-CoV-2 spike protein on the BBB. Our findings provide insight into the continued theme that this novel coronavirus triggers responses at the endothelium. Specifically, regarding the brain endothelium, the SARS-CoV-2 spike protein-induced destabilization of the BBB promoted a pro-inflammatory status but did not appear to alter cell viability acutely. Dysfunction of the barrier offers a plausible explanation to the observed neurological complications seen in COVID-19. Lastly, the opening of the BBB hints at the possible means in which the SARS-CoV-2 pathogen could also neuroinvade.'