Involvement of the nervous system in COVID-19: The bell should toll in the brain

Abstract

The world is fuming at SARS-CoV-2 for being the culprit for causing the devastating COVID-19, claiming millions of lives across the globe in the form of respiratory disorders. But lesser known are its effects on the CNS that are slowly surfacing in the worldwide population. Our review illustrates findings that claim SARS-CoV-2's arrival onto the ACE2 receptors of neuronal and glial cells mainly via CSF, olfactory nerve, trigeminal nerve, neuronal dissemination, and hematogenous pathways. The role of SARS-CoV-2 structural proteins in its smooth viral infectivity of the host cannot be ignored, especially the spike proteins that mediate spike attachment and host membrane fusion. Worth mentioning the nucleocapsid, envelope, and membrane proteins make the proliferation of SARS-CoV-2 much simpler than expected in spreading infection. This has led to catastrophic conditions like seizures, Guillain-Barré syndrome, viral encephalitis, meningoencephalitis, acute cerebrovascular disease, and respiratory failures. Placing a magnifying lens on the lesser-explored CNS consequences of COVID-19, we attempt to shift the focus of our readers onto the new supporting threats to which further studies are needed.

Keywords: ACE2 receptor; COVID-19; Coronavirus; Entry; Mechanisms; Nervous system; Neurological disorder; SARS-CoV-2.

Graphical abstract

Fig. 1

The development of SARS-CoV-2 antibodies after its infection in the CSF.

Fig. 2

The entry of SARS-CoV-2 in the CNS via the olfactory sensory neurons.

Fig. 3

Nucleus tractus solitarius infection by SARS-CoV-2 via the trigeminal nerve pathway.

Fig. 4

The hematogenous route used by SARS-CoV-2 to infect neurons in the CNS.

Fig. 5

Interaction of SARS-CoV-2 spike protein with ACE2 receptors at multiple sites to facilitate CNS damage.