Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms

• Published in: Journal of Neurology 2020-08, Vol.267 (8), p.2179-2184
• Main Authors: Zhou, Zhiqiang, Kang, Huicong, Li, Shiyong, Zhao, Xu
• Format: Article
• Language: English
• Subjects: ACE2; Angiotensin; Angiotensin-converting enzyme 2; Animals; Betacoronavirus; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - pathology; Blood-Brain Barrier - virology; Brain - metabolism; Brain - pathology; Brain - virology; Central nervous system; Cerebrospinal fluid; Cerebrovascular diseases; Coronavirus Infections - diagnosis; Coronavirus Infections - epidemiology; Coronavirus Infections - metabolism; Coronaviruses; COVID-19; Dizziness - diagnosis; Dizziness - epidemiology; Dizziness - metabolism; Encephalitis; Encephalitis - diagnosis; Encephalitis - epidemiology; Encephalitis - metabolism; Encephalopathy; Glial cells; Headache; Headache - diagnosis; Headache - epidemiology; Headache - metabolism; Hemorrhage; Humans; Ischemia; Medicine; Medicine & Public Health; Meningitis; Nervous System Diseases - diagnosis; Nervous System Diseases - epidemiology; Nervous System Diseases - metabolism; Neurology; Neuronal-glial interactions; Neuroradiology; Neurosciences; Pandemics; Peptidyl-dipeptidase A; Pneumonia, Viral - diagnosis; Pneumonia, Viral - epidemiology; Pneumonia, Viral - metabolism; Review; Ribonucleic acid; RNA; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Subarachnoid hemorrhage; Thrombosis
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-020-09929-7

Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus (SARS-CoV-2), has become a global pandemic threat. The potential involvement of COVID-19 in central nervous system (CNS) has attracted considerable attention due to neurological manifestations presented throughout the disease process. In addition, SARS-CoV-2 is structurally similar to SARS-CoV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Thus, cells expressing ACE2, such as neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 infection. Here, we have reviewed the neurological characteristics of COVID-19 and summarized possible mechanisms of SARS-CoV-2 invasion of the CNS. COVID-19 patients have presented with a number of different neurological symptoms such as headache, dizziness, hyposmia, and hypogeusia during the course of illness. It has also been reported recently that some cases of COVID-19 have presented with concurrent acute cerebrovascular disease (acute ischemic stroke, cerebral venous sinus thrombosis, cerebral hemorrhage, subarachnoid hemorrhage), meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and acute Guillain–Barré syndrome. Furthermore, SARS-CoV-2 RNA detected in a cerebrospinal fluid specimen of a patient with COVID-19 have provided direct evidence to support the theory of neurotropic involvement of SARS-CoV-2. However, the underlying neurotropic mechanisms of SARS-CoV-2 are yet to be established. SARS-CoV-2 may affect CNS through two direct mechanisms (hematogenous dissemination or neuronal retrograde dissemination) or via indirect routes. The underlying mechanisms require further elucidation in the future.