Molecular Mechanisms of SARS-CoV-2/COVID-19 Pathogenicity on the Central Nervous System: Bridging Experimental Probes to Clinical Evidence and Therapeutic Interventions

Adv Exp Med Biol. 2022:1376:1-27. doi: 10.1007/5584_2021_675.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has dramatically impacted the global healthcare systems, constantly challenging both research and clinical practice. Although it was initially believed that the SARS-CoV-2 infection is limited merely to the respiratory system, emerging evidence indicates that COVID-19 affects multiple other systems including the central nervous system (CNS). Furthermore, most of the published clinical studies indicate that the confirmed CNS inflammatory manifestations in COVID-19 patients are meningitis, encephalitis, acute necrotizing encephalopathy, acute transverse myelitis, and acute disseminated encephalomyelitis. In addition, the neuroinflammation along with accelerated neurosenescence and susceptible genetic signatures in COVID-19 patients might prime the CNS to neurodegeneration and precipitate the occurrence of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. Thus, this review provides a critical evaluation and interpretive analysis of existing published preclinical as well as clinical studies on the key molecular mechanisms modulating neuroinflammation and neurodegeneration induced by the SARS-CoV-2. In addition, the essential age- and gender-dependent impacts of SARS-CoV-2 on the CNS of COVID-19 patients are also discussed.

Keywords: COVID-19; Neurodegeneration; Neuroinflammation; Neuroinvasion; Neurosenescence; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • COVID-19*
  • Central Nervous System
  • Humans
  • Nervous System Diseases*
  • Pandemics
  • SARS-CoV-2
  • Virulence