Fig. 4

SARS-CoV-2 interaction and transport across the BBB. Normal and infected neurovascular unit (NVU). A normal BBB restricts and controls the entry of substances in and out of the brain. Tight junctions between endothelial cells restrict the movement via the paracellular route for small molecules, like ions (e.g., potassium, sodium). Along with this tight barrier there is also low levels of pinocytosis, numerous transporters for select molecules, and efflux pumps to remove substances from the brain into the blood. In an infected/diseased BBB, there is the possibilities that tight junctions loosen, allowing larger molecules to pass via the paracellular route into the brain, decrease in efflux pumps and transporters as well as increased pinocytosis altering the balance across the barrier. Basement membrane breakdown on the abluminal surface can cause increase the barrier permeability. Viral infection can cause the release of cytokines, which can alter the integrity of the BBB and increase immune cell penetration into the brain