Covert Pathways to the Cranial Cavity: Could These Be Potential Routes of SARS-CoV-2 to the Brain?

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) induced central nervous system disease has now been recognized as a complication of coronavirus disease (COVID-19) in addition to its multisystem organ infection. How does the central nervous system (CNS) get involved? The possible routes by which SARS-CoV-2 enters the CNS is now an active niche of research worldwide. We had previously hinted the pathway via the nose to the brain across the olfactory mucosa and cribriform plate. Here we detail three pathways by which the infection can ascend to the brain and have highlighted routes that can lead to CNS involvement from other body cavities like the mouth and pharynx. The spaces contained within the ensheathed olfactory nerves connected to the cerebrospinal fluid of the cranial cavity, in particular, has been described in addition to other routes of ascending infection toward the CNS. We implore others to investigate these covert yet important passages to understand the pathogenesis of Neuro-COVID in our fight against SARS-CoV-2 that has changed the lives of the human race in the ongoing pandemic.