Neurological manifestations and pathogenic mechanisms of COVID-19

Abstract

Coronavirus disease (COVID-19) arising from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection has caused a worldwide pandemic, mainly owing to its highly virulent nature stemming from a very strong and highly efficacious binding to the angiotensin converting enzyme-2 (ACE2) receptor. As the pandemic developed, increasing numbers of COVID-19 patients with neurological manifestations were reported, strongly suggesting a causal relationship. Indeed, direct invasion of SARS-CoV-2 viral particles into the brain can occur through the cribriform plate via olfactory nerves, passage through a damaged blood-brain-barrier, or via haematogenic infiltration of infected leukocytes. Neurological complications range from potentially fatal encephalopathy and stroke, to the onset of headaches and dizziness, which despite their apparent innocuous presentation may still imply a more sinister pathology. Here, we summarize the most recent knowledge on the neurological presentations typically being associated with COVID-19, whilst providing potential pathophysiological mechanisms. The latter are centered upon hypoxic brain injury, generation of a cytokine storm with attendant immune-mediated damage, and a prothrombotic state. A better understanding of both the neuroinvasive properties of SARS-CoV-2 and the neurological complications of COVID-19 will be important to improve patient outcomes.