Understanding the Immunologic Characteristics of Neurologic Manifestations of SARS-CoV-2 and Potential Immunological Mechanisms

Mol Neurobiol. 2020 Dec;57(12):5263-5275. doi: 10.1007/s12035-020-02094-y. Epub 2020 Sep 1.

Abstract

Similar to its predecessors, coronavirus disease 2019 (COVID-19) exhibits neurotrophic properties, which lead to progression of neurologic sequelae. Besides direct viral invasion to the central nervous system (CNS), indirect CNS involvement through viral-mediated immune response is plausible. Aberrant immune pathways such as extreme release of cytokines (cytokine storm), autoimmunity mediated by cross-reactivity between CNS components and viral particles, and microglial activation propagate CNS damage in these patients. Here, we review the currently available evidence to discuss the plausible immunologic pathways that may contribute to the development of COVID-19 neurological complications, namely Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, Guillain-Barre syndrome, seizure, and brainstem involvement.

Keywords: Central nervous system; Coronavirus disease 2019; Cytokines; Immunologic pathways; Neurological complications; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus* / immunology
  • Betacoronavirus* / pathogenicity
  • Brain Stem / physiopathology
  • Brain Stem / virology
  • COVID-19
  • Coronavirus Infections / complications*
  • Coronavirus Infections / epidemiology
  • Coronavirus Infections / immunology
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / immunology
  • Cytopathogenic Effect, Viral
  • Disease Outbreaks
  • Guillain-Barre Syndrome / etiology
  • Guillain-Barre Syndrome / immunology
  • Humans
  • Mice
  • Multiple Sclerosis / etiology
  • Multiple Sclerosis / immunology
  • Nerve Tissue Proteins / physiology
  • Nervous System Diseases / etiology*
  • Nervous System Diseases / immunology
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / immunology
  • Neuroglia / pathology
  • Neuroglia / virology
  • Neurons / pathology
  • Neurons / virology
  • Pandemics*
  • Peptidyl-Dipeptidase A / physiology
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / immunology
  • Receptors, Virus / physiology
  • Respiratory Insufficiency / etiology
  • Respiratory Insufficiency / physiopathology
  • SARS-CoV-2
  • Seizures / etiology
  • Seizures / immunology
  • Severe Acute Respiratory Syndrome / complications
  • Severe Acute Respiratory Syndrome / epidemiology
  • Stroke / etiology
  • Stroke / immunology

Substances

  • Nerve Tissue Proteins
  • Receptors, Virus
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2