SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

Manuela Pennisi, Giuseppe Lanza, Luca Falzone, Francesco Fisicaro, Raffaele Ferri, Rita Bella

Research output: Contribution to journalReview articlepeer-review


Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called "cytokine storm"), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Issue number15
Publication statusPublished - Jul 31 2020


  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus/isolation & purification
  • Blood-Brain Barrier/metabolism
  • Brain Diseases/complications
  • COVID-19
  • Central Nervous System/metabolism
  • Coronavirus Infections/pathology
  • Encephalitis/complications
  • Humans
  • Pandemics
  • Peptidyl-Dipeptidase A/metabolism
  • Pneumonia, Viral/pathology
  • SARS-CoV-2


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