Neurological manifestations of patients with COVID-19: potential routes of SARS-CoV-2 neuroinvasion from the periphery to the brain

Front Med. 2020 Oct;14(5):533-541. doi: 10.1007/s11684-020-0786-5. Epub 2020 May 4.


Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), has caused a global pandemic in only 3 months. In addition to major respiratory distress, characteristic neurological manifestations are also described, indicating that SARS-CoV-2 may be an underestimated opportunistic pathogen of the brain. Based on previous studies of neuroinvasive human respiratory coronaviruses, it is proposed that after physical contact with the nasal mucosa, laryngopharynx, trachea, lower respiratory tract, alveoli epithelium, or gastrointestinal mucosa, SARS-CoV-2 can induce intrinsic and innate immune responses in the host involving increased cytokine release, tissue damage, and high neurosusceptibility to COVID-19, especially in the hypoxic conditions caused by lung injury. In some immune-compromised individuals, the virus may invade the brain through multiple routes, such as the vasculature and peripheral nerves. Therefore, in addition to drug treatments, such as pharmaceuticals and traditional Chinese medicine, non-pharmaceutical precautions, including facemasks and hand hygiene, are critically important.

Keywords: SARS-CoV-2; brain; coronavirus disease 2019 (COVID-19); neuroinvasion; neurological manifestations.

Publication types

  • Review

MeSH terms

  • Betacoronavirus* / pathogenicity
  • Betacoronavirus* / physiology
  • Coronavirus Infections* / immunology
  • Coronavirus Infections* / physiopathology
  • Coronavirus Infections* / virology
  • Humans
  • Nervous System Diseases* / etiology
  • Nervous System Diseases* / immunology
  • Nervous System Diseases* / therapy
  • Nervous System* / physiopathology
  • Nervous System* / virology
  • Pandemics*
  • Pneumonia, Viral* / immunology
  • Pneumonia, Viral* / physiopathology
  • Pneumonia, Viral* / virology

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2