COVID-19-Associated Neurological Disorders: The Potential Route of CNS Invasion and Blood-Brain Relevance

Cells. 2020 Oct 27;9(11):2360. doi: 10.3390/cells9112360.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that has sparked a global pandemic of the coronavirus disease of 2019 (COVID-19). The virus invades human cells through the angiotensin-converting enzyme 2 (ACE2) receptor-driven pathway, primarily targeting the human respiratory tract. However, emerging reports of neurological manifestations demonstrate the neuroinvasive potential of SARS-CoV-2. This review highlights the possible routes by which SARS-CoV-2 may invade the central nervous system (CNS) and provides insight into recent case reports of COVID-19-associated neurological disorders, namely ischaemic stroke, encephalitis, encephalopathy, epilepsy, neurodegenerative diseases, and inflammatory-mediated neurological disorders. We hypothesize that SARS-CoV-2 neuroinvasion, neuroinflammation, and blood-brain barrier (BBB) dysfunction may be implicated in the development of the observed disorders; however, further research is critical to understand the detailed mechanisms and pathway of infectivity behind CNS pathogenesis.

Keywords: CNS; COVID-19; SARS-CoV-2; blood-brain barrier; cerebrovascular; neurological disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / immunology
  • Betacoronavirus / metabolism*
  • Blood-Brain Barrier / physiopathology*
  • Blood-Brain Barrier / virology*
  • COVID-19
  • Coronavirus Infections / complications*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Cytokines / metabolism
  • Humans
  • Nervous System Diseases / complications*
  • Pandemics
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • SARS-CoV-2
  • Virus Internalization*

Substances

  • Cytokines
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2