SARS-CoV-2 infection's pathogenesis: Take-home messages from other pathogens
The proven endotheliotropic attitude of SARS-CoV-2, coupled with its documented ability to colonize the gastrointestinal tract (GIT) of both human hosts (as nicely highlighted in this very interesting article) and experimentally infected animals like cats (1), is a matter of growing concern.
In this respect, alongside the highly plausible possibility that SARS-CoV-2 may infect the central nervous system (CNS) following haematogenous spread to the brain and, still to be proven, also via the neuro-olfactory epithelium (with anosmia being one of the clinical signs comprising the CoViD-19 disease spectrum), it should be adequately taken into account that viral neuroinvasion could also occur from the enteric nervous system plexuses lining the GIT wall.
Indeed, this peculiar neuroinvasion modality is supported by previous studies addressing prion disease pathogenesis, with special reference to those carried out on Scrapie, the prion disease "prototype" (2).
Furthermore, I believe that adequate attention should be also placed upon the possibility that, once in the CNS, SARS-CoV-2 could become "encoated" by cyclophyllin(s), a host molecule interacting with CD147 (a gamma-secretase subunit), which has been recently suggested to act as an additional receptor for SARS-CoV-2. Noteworthy, a cyclophyllin-A and a cyclophyllin-B "coat" have been already shown to be "worn", respectively, by SARS-CoV and Measles virus (3), with such a mechanism allowing these two viral pathogens to escape the host's immune response at the level of brain tissue, where the immune response is already known to be "attenuated" as compared to many other body sites.
1) Shi J., et al. (2020) - Science.
2) Marruchella G., et al. (2007) - J. Gen. Virol.
3) Di Guardo G. (2012) - Front. Microbiol.
Competing interests: No competing interests