Models and theories investigating the interactions of SARS-CoV-2 infection with the blood-brain barrier

The neurological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain largely unclear. With the ever-mounting concerns surrounding the neurological harm of SARS-CoV-2, it is important to elucidate these effects and how they transpire. Given that these symptoms include an altered mental status in some cases (including brain fog, headaches, sleep impairment, etc.), it is believed that SARS-CoV-2 must somehow access the central nervous system (CNS), whether by direct infection by virions or by indirect means (1, 2). There is often disagreement as to whether SARS-CoV-2 directly infects the blood-brain barrier (BBB) to gain entry to the CNS. Certain research groups speculate that SARS-CoV-2 harms the CNS indirectly. Studies have found that the viral S1 protein, cleaved off by host furin during entry of the virus into cells, has the ability to pass the BBB, and may be partially responsible for the neurological symptoms exhibited (3). Regardless of what theory is being investigated, to examine the interactions of SARS-CoV-2 on the BBB, an accurate model is necessary. The models and experiments examined in this paper suggest that SARS-CoV-2 BBB invasion is possible, but the mechanism by which this occurs is still uncertain. However, models such as these can be used to continue experimentation and eventually discover how SARS-CoV-2 gains access to the CNS.