Figure 2.

Potential mechanism of CNS invasion by SARS-CoV-2. (1) The blood−brain barrier (BBB) permits a limited exchange, due to the continuous capillary endothelium, with a tight junction supported by continuous basement membrane and surrounded by astrocyte feet. Monocytes infected with SARS-CoV-2 act as Trojan horses, due to their access to the CNS. Thus, an extravasation of infected monocytes can promote CNS infection. (2) The high-spectrum olfactory receptors expressed on the cilia of olfactory neurons may act as receptors for SARS-CoV-2, thus infecting the bipolar neuron in the nasal epithelium. Retrograde movement leads SARS-CoV-2 to the olfactory bulb, which is connected to the limbic system, thus promoting the invasion of the limbic system, including the hippocampus. (3) Chemoreceptive neuron infection in the lower respiratory tract may lead to a retrograde migration of the virus through the nervous network toward the respiratory center in the brain stem, resulting in acute respiratory failure. Created with BioRender.com