How coronaviruses gain entry into the nervous system

Coronaviruses are neurotropic and potentially neurovirulent (Desforges, Le Coupanec et al. 2019). Like SARS-CoV, SARS‐CoV2 exploits the receptor angiotensin converting enzyme 2 (ACE2) to gain entry inside the cells. In humans, ACE2 is expressed in the capillary endothelium, as well as in the brain, offering some potential sites of interaction between the virus and its receptor (Baig, Khaleeq et al. 2020). An interesting hypothesis has emerged around the use of angiotensin-converting enzyme (ACE) inhibitors to treat diabetes, which leads to increased expression of ACE2, making the cells more vulnerable to infection with the virus. Clinical studies are underway to test this hypothesis. Yet, the presence of ACE2 is not sufficient to make host cells susceptible to infection.

Autopsies from SARS patients in 2002 have demonstrated the presence of SARS CoV particles in their brain (Li, Bai et al. 2020). While Acute Hemorrhagic Necrotizing Encephalopathy has been described for SARSCov2 (Poyiadji, Shahin et al. 2020), the SARS Cov2 has been detected by gene sequencing in the CSF of one patient (Özdağ Acarli, Samanci et al. 2020) who received a diagnosis of viral encephalitis.

Experiments in mice revealed that the SARS CoV and MERS CoV given intranasally were able to enter the brain, probably via the olfactory nerves, heavily infecting the brainstem. Even though the exact route used by the virus is not definitely proven, it has been suggested that it might first invade the peripheral nerve terminals, and then gain access to the CNS via a trans-synaptic route (Li, Bai et al. 2020). Furthermore, some coronaviruses have been shown to spread via a trans-synaptic route to the medullary cardiorespiratory center from the mechanoreceptors and chemoreceptors in the lung and lower respiratory airways. Could the anosmia observed in some CoVid 19 patients reflect the involvement of the olfactory bulbs? Could SARS Cov2 infect the nucleus of the solitary tract and nucleus ambiguous, potentially destroying medullary neurons and from there on, induce acute respiratory failure of patients with COVID‐19 (Li, Bai et al. 2020)?

PP

Viral infections, neurodegenerative & psychiatric diseases: an arduous search for clues …

Viruses & Acute infections

Encephalitis with an infectious cause is frequent, among which viral encephalitis represents an important proportion. Encephalitis is ... read more