Neurological Manifestations of COVID-19 and Other Coronavirus Infections: A Systematic Review

Clin Neurol Neurosurg. 2020 Jul;194:105921. doi: 10.1016/j.clineuro.2020.105921. Epub 2020 May 15.


Background: Increasing research reports neurological manifestations of COVID-19 patients. SARS-CoV-2 shares homology with other human coronaviruses that have also had nervous system involvement.

Objective: To review the neurological aspects of SARS-cov2 and other coronavirus, including transmission pathways, mechanisms of invasion into the nervous system, and mechanisms of neurological disease.

Methods: We conducted a systematic review of articles in PubMed, SCOPUS and EMBASE data bases. Reviewed evidence is presented in sections of this manuscript which includes pathogenesis, neuro-invasion, encephalitis, Guillain-Barré, ADEM, multiple sclerosis, polyneuropathy, and cerebrovascular disease.

Results: A total 67 studies were included in the final analysis of experimental studies, case reports, series of cases, cohort studies, and systematic reviews related to neurological manifestations of SARS- CoV-2 and other human coronavirus infections. The SARS-CoV-2 receptor is expressed in the nervous system. Common reported symptoms included hyposmia, headaches, weakness, altered consciousness. Encephalitis, demyelination, neuropathy, and stroke have been associated with COVID-19. Infection through the cribriform plate and olfactory bulb and dissemination through trans-synaptic transfer are some of the mechanisms proposed. Invasion of the medullary cardiorespiratory center by SARS-CoV-2 may contribute to the refractory respiratory failure observed in critically-ill COVID-19 patients.

Conclusion: An increasing number of reports of COVID-19 patients with neurological disorders add to emergent experimental models with neuro-invasion as a reasonable concern that SARS-CoV-2 is a new neuropathogen. How it may cause acute and chronic neurologic disorders needs to be clarified in future research.

Keywords: COVID-19; Coronavirus; Encephalitis; Neurological manifestations; SARS-CoV-2.

Publication types

  • Case Reports
  • Systematic Review

MeSH terms

  • Betacoronavirus*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / virology
  • Coronavirus Infections / diagnostic imaging*
  • Coronavirus Infections / epidemiology*
  • Coronavirus Infections / metabolism
  • Humans
  • Nervous System Diseases / diagnostic imaging*
  • Nervous System Diseases / epidemiology*
  • Nervous System Diseases / metabolism
  • Observational Studies as Topic / methods
  • Pandemics
  • Pneumonia, Viral / diagnostic imaging*
  • Pneumonia, Viral / epidemiology*
  • Pneumonia, Viral / metabolism

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2