Fig. 1.

Transmission routes of coronaviruses into the CNS. (1) Intranasal inoculation of coronaviruses can lead to neuroinvasion through primary olfactory neurons in the olfactory epithelium and mitral/tufted cells in the olfactory bulb. (2) Infected monocytes can cross from BBB via diapedesis and infect glial and neuronal cells. (3) Interaction between CoV and ACE2 receptors on BBB endothelial cells can enter into the CNS. (4) Finally, viruses can enter the CNS through peripheral nerves via trans-synaptic transmission. ACE2, angiotensin-converting enzyme 2; CNS, central nervous system; PNS, peripheral nervous system