Neurological Complications Associated with the Blood-Brain Barrier Damage Induced by the Inflammatory Response During SARS-CoV-2 Infection

Mol Neurobiol. 2021 Feb;58(2):520-535. doi: 10.1007/s12035-020-02134-7. Epub 2020 Sep 25.


The main discussion above of the novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has focused substantially on the immediate risks and impact on the respiratory system; however, the effects induced to the central nervous system are currently unknown. Some authors have suggested that SARS-CoV-2 infection can dramatically affect brain function and exacerbate neurodegenerative diseases in patients, but the mechanisms have not been entirely described. In this review, we gather information from past and actual studies on coronaviruses that informed neurological dysfunction and brain damage. Then, we analyzed and described the possible mechanisms causative of brain injury after SARS-CoV-2 infection. We proposed that potential routes of SARS-CoV-2 neuro-invasion are determinant factors in the process. We considered that the hematogenous route of infection can directly affect the brain microvascular endothelium cells that integrate the blood-brain barrier and be fundamental in initiation of brain damage. Additionally, activation of the inflammatory response against the infection represents a critical step on injury induction of the brain tissue. Consequently, the virus' ability to infect brain cells and induce the inflammatory response can promote or increase the risk to acquire central nervous system diseases. Here, we contribute to the understanding of the neurological conditions found in patients with SARS-CoV-2 infection and its association with the blood-brain barrier integrity.

Keywords: Blood-brain barrier; COVID-19; Inflammatory response; Neurological complications; Neurotropism; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Blood-Brain Barrier / pathology
  • Blood-Brain Barrier / virology*
  • Brain / pathology
  • Brain / virology*
  • COVID-19 / complications*
  • COVID-19 / pathology
  • Central Nervous System Diseases / pathology
  • Central Nervous System Diseases / virology*
  • Humans
  • Inflammation / pathology
  • Inflammation / virology*