COVID-19 and neurological symptoms: is the SARS-CoV-2 virus neurotropic?

Importance: The most notable symptoms of the Coronavirus Disease 2019 (COVID-19) pandemic are fever, cough, dyspnea, and in severe cases, adult respiratory distress syndrome (ARDS.) But neurological symptoms including confusion, stroke, and encephalopathy are reported, and anosmia and hypogeusia are also common indicating that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be neurotropic.

Observations: The SARS-Co-1 and 2 viruses bind to angiotensin converting enzyme 2 (ACE2), which is present on human brain endothelium and non-neuronal cells in the nasopharynx and lingual epithelium. However, SARS-CoV-1 and 2 do not bind rodent ACE2 avidly, which has required the generation of humanized ACE2 transgenic animal models of disease. Transgenic mouse models suggest that the SARS- CoV-1 and Middle East respiratory syndrome (MERS)-CoV are neurotropic and infect and damage the brain, including the cardiorespiratory centers in the medulla. The symptoms of anosmia and hypogeusia indicate a portal to the brain. The relationship between encephalitis lethargica and post encephalitis parkinsonism to the Spanish Flu (H1N1 influenza virus) is unclear but raises the question of long term neurological complications of pandemics.

Conclusions and relevance: There is a concern that there may be long term neurological sequelae of infection with SARS-CoV-2. Registries and long term neurological follow up with longitudinal cohort studies of COVID19 positive patients are needed.