Fig. 1.

According to pre-clinical model based on SARS-CoV, in the first phase of neuroinvasion the virus follows a trans-synaptic pathway along the olfactory nerve reaching the entorhinal cortex. Minimal or no respiratory symptoms are detected and CoV replication increases the viral load in CSF (blue curve). In the “CNS clearance” phase, CoV could be located in the brainstem (e.g. nucleus of the solitary tract) affecting the respiratory drive. The viral load in CSF progressively decreases but, on the contrary, SARS-CoV-2 could be detected in respiratory secretions by nasopharyngeal swab (yellow hyperbole). In the last phase, the respiratory system is severely affected leading to potential hypoxia with subsequent brain damage. IP, Interstitial pneumonia. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)