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.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• neuroinvasion
• central nervous system disorders
• peripheral nervous system disorders

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.

Notes on contributors

Matteo Galea

Matteo Galea is a medical student enrolled in the M.D. programme of the University of Malta Medical School, Mater Dei Hospital.

Michaela Agius

Michaela Agius is a medical student enrolled in the M.D. programme of the University of Malta Medical School, Mater Dei Hospital.

Neville Vassallo

Neville Vassallo is an associate professor in neurophysiology within the Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, of the University of Malta. He is also an accredited Specialist in Family Medicine with the Ministry for Health, Malta.