Neurological Complications of COVID-19 and Possible Neuroinvasion Pathways: A Systematic Review

Int J Environ Res Public Health. 2020 Sep 14;17(18):6688. doi: 10.3390/ijerph17186688.


The Coronavirus Disease 2019 (COVID-19) outbreak has shocked the whole world with its unexpected rapid spread. The virus responsible for the disease, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), enters host cells by means of the envelope spike protein, which binds to angiotensin-converting enzyme 2 receptors. These receptors are highly expressed in heart, lungs, respiratory tract epithelium, endothelial cells and brain. Since an increasing body of significant evidence is highlighting a possible neuroinvasion related to SARS-CoV-2, a state of the art on the neurological complications is needed. To identify suitable publications, our systematic review was carried out by searching relevant studies on PubMed and Scopus databases. We included studies investigating neurologic manifestations of SARS-CoV-2 in patients over 18. According to the analyzed studies, the most frequent disorders affecting central nervous system (CNS) seem to be the following: olfactory and taste disorders, ischemic/hemorrhagic stroke, meningoencephalitis and encephalopathy, including acute necrotizing encephalopathy, a rare type of encephalopathy. As regards the peripheral nervous system (PNS), Guillain-Barré and Miller Fisher syndromes are the most frequent manifestations reported in the literature. Important clinical information on the neurological manifestations of SARS-CoV-2 would help clinicians raise awareness and simultaneously improve the prognosis of critically ill patients.

Keywords: COVID-19; SARS-CoV-2; neurologic complications.

Publication types

  • Systematic Review

MeSH terms

  • Betacoronavirus
  • Central Nervous System Diseases / virology*
  • Coronavirus Infections / complications*
  • Guillain-Barre Syndrome / virology
  • Humans
  • Miller Fisher Syndrome / virology
  • Pandemics
  • Pneumonia, Viral / complications*

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2