How SARS-Cov-2 can involve the central nervous system. A systematic analysis of literature of the department of human neurosciences of Sapienza University, Italy

Abstract

Italy is currently one of the countries most affected by the global emergency of COVID-19, a lethal disease of a novel coronavirus renamed as SARS-CoV-2. SARS-CoV-2 shares highly homological sequence with the most studied SARS-CoV, and causes acute, highly deadly pneumonia (COVID-19) with clinical symptoms similar to those reported for SARS-CoV and MERS-CoV. Increasing evidence shows that these coronaviruses are not always confined to the respiratory tract and that they may also neuroinvasive and neurotropic, with potential neuropathological consequences in vulnerable populations. The aim of this study is to predict a likely CNS involvement by SARS-CoV-2 by studying the pathogenic mechanisms in common with other better known and studied coronaviruses with which it shares the same characteristics. Understanding the mechanisms of neuroinvasion and interaction of HCoV (including SARS-Cov-2) with the CNS is essential to evaluate potentially pathological short- and long-term consequences. Autopsies of the COVID-19 patients, detailed neurological investigation, and attempts to isolate SARS-CoV-2 from the endothelium of cerebral microcirculation, cerebrospinal fluid, glial cells, and neuronal tissue can clarify the role played by COVID-19 in CNS-involvement and in the ongoing mortalities as has been in the recent outbreak.

Keywords: Brain; Central nervous system; Covid-19; Human coronavirus; Italy; Neuroscience; SARS-Cov-2.

Fig. 1

A prisma Flow-diagram for selection of studies.

Fig. 2

A schematic representation of the possible spreading of SARS-CoV-2 to CSN drawn by the author. SARS-COV-2 uses severals mRNA encoding proteins, such S1 protein that enables the attachment of the virion to the cell membrane by interacting with the host ACE2 receptor. Viral S and E proteins, structural and accessory proteins are important factors of neurovirulence, neuropropagation and neurodegeneration of infected cells. HCoV may lead to the disruption of the nasal epithelium and across the cribriform plate of the ethmoid bone close to the olfactory bulb uses as the main entry route into the CNS the olfactory nerve fibers. The virus disseminates to several different regions of the brain and the brainstem via a synapse-connected route to the medullary cardiorespiratory center, may also partially explain why some of the patients developed respiratory failure (upper part of scheme). The second hypothesized pattern of spreading within the CNS is through neuronal dissemination, where a given virus infects neurons in the periphery using the mechanisms of active transport within those cells to gain access to the CNS (lower part of scheme).