Infectivity of human coronavirus in the brain

Abstract

A new strain of human coronaviruses (hCoVs), Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been identified to be responsible for the current outbreak of the coronavirus disease 2019 (COVID-19). Though major symptoms are primarily generated from the respiratory system, neurological symptoms are being reported in some of the confirmed cases, raising concerns of its potential for intracranial invasion and neurological manifestations, both in the acute phase and in the long-term. At present, it remains unclear the extent to which SARS-CoV-2 is present in the brain, and if so, its pathogenic role in the central nervous system (CNS). Evidence for neuroinvasion and neurovirulence of hCoVs has been recognised in animal and human studies. Given that SARS-CoV-2 belongs to the same family and shares characteristics in terms of receptor binding properties, it is worthwhile exploring its potential CNS manifestations. This review summarises previous findings from hCoVs in relation to the CNS, and compares these with the new strain, aiming to provide a better understanding of the effects of SARS-CoV-2 on the CNS.

Keywords: Brain; Coronavirus; Human; Neuroinvasion; Neurological manifestation; SARS-CoV-2.

Fig. 1

Possible dissemination routes of CNS infection with hCoVs. Route 1 (yellow solid arrows): olfactory nerve to olfactory cortex of temporal lobe to hippocampus to amygdala, or to hypothalamus; Route 2 (green dot arrows): via serotoninergic dorsal raphe system; Route 3 (red dot arrows): via hematogenous route and Virchow-Robin spaces; Route 4 (gray dot arrows): via lymphatic system. Dissemination routes with empiric data are indicated by solid arrows, and speculative ones are indicated by dot arrows. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)