Fig. 1.

A schematic drawing of the SARS-CoV-2 invasion pathways in the brain.

SARS-CoV-2 can access the brain via the olfactory nerve or blood circulation. (A) In route 1, the virus is carried by the axons of the olfactory sensory neurons into the OLB towards the PVN. SARS-CoV-2 is transported to the cytoplasm mediated by ACE2 and proteases in PVN. Subsequently, the viral RNA is replicated, transcribed, and translated by viral proteins inside the cell. The viral protein and RNA are assembled to constitute a new virion to be released in the neuronal membrane. (B) In route 2, the SARS-CoV-2 moves from blood to extracellular fluid in circumventricular organs. This virus can enter SFO neurons through ACE2. Axonal projections from the SFO synapse on PVN and SON neurons, which regulates the hydroelectrolytic balance. SARS-CoV-2 infection can disrupt the SFO and PVN functions, leading to hydroelectrolytic imbalance. ACE2, angiotensin-converting enzyme 2; OLB, bulb olfactory; PVN, paraventricular hypothalamic nucleus; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SFO, subfornical organ; SON, supraoptic hypothalamic nucleus.