Does coronaviruses induce neurodegenerative diseases? A systematic review on the neurotropism and neuroinvasion of SARS-CoV-2

Drug Discov Ther. 2021 Jan 23;14(6):262-272. doi: 10.5582/ddt.2020.03106. Epub 2020 Dec 31.


The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in 2019 in Wuhan, China. Clinically, respiratory tract symptoms as well as other organs disorders are observed in patients positively diagnosed coronavirus disease 2019 (COVID-19). In addition, neurological symptoms, mainly anosmia, ageusia and headache were observed in many patients. Once in the central nervous system (CNS), the SARS-CoV-2 can reside either in a quiescent latent state, or eventually in actively state leading to severe acute encephalitis, characterized by neuroinflammation and prolonged neuroimmune activation. SRAS-CoV-2 requires angiotensin-converting enzyme 2 (ACE2) as a cell entry receptor. The expression of this receptor in endothelial cells of blood-brain barrier (BBB) shows that SRAS-CoV-2 may have higher neuroinvasive potential compared to known coronaviruses. This review summarizes available information regarding the impact of SRAS-CoV-2 in the brain and tended to identify its potential pathways of neuroinvasion. We offer also an understanding of the long-term impact of latently form of SARS-CoV-2 on the development of neurodegenerative disorders. As a conclusion, the persistent infection of SRAS-CoV-2 in the brain could be involved on human neurodegenerative diseases that evolve a gradual process, perhapes, over several decades.

Keywords: SRAS-CoV-2; neurodegenerative diseases; neuroinvasion; neurotropism.

Publication types

  • Systematic Review

MeSH terms

  • Animals
  • COVID-19 / complications
  • COVID-19 / virology*
  • Central Nervous System Viral Diseases / metabolism
  • Central Nervous System Viral Diseases / pathology
  • Central Nervous System Viral Diseases / virology*
  • Host-Pathogen Interactions
  • Humans
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Neurodegenerative Diseases / virology*
  • Neurons / metabolism
  • Neurons / pathology
  • Neurons / virology*
  • SARS-CoV-2 / pathogenicity*
  • Viral Tropism*
  • Virus Latency