Fig. 3

Possible routes of brain invasion. SARS-CoV-2 may enter the CNS through the olfactory system (A) cross the neural-mucosal interface in the olfactory mucosa, infect the olfactory neurons and then migrate up to the medulla oblongata. The virus can also take a route through the trigeminal nerve (B), infecting it in the nasal cavity. Other potential routes of neuroinvasion by SARS-CoV2 include pathways of retrograde synaptic transport via axons from receptors in the lung (C) and via the vagus nerve from enteric nervous system (D). The brain invasion may occur by disrupting the BBB (E), and by compromising the function of the choroid plexus (F). This can lead to the triggering of a neuroinflammatory response and promote the cerebral inflammatory state

Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus type 2; ACE2: angiotensin-converting enzyme 2; TJ: tight junctions; BV: blood vessel; CP: choroid plexus; EC: epithelial cell; CSF cerebrospinal fluid; NS: nervous system; VN: vagus nerve.