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Blood-brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated

Chris Greene1, Ruairi Connolly2, Declan Brennan2

  • 1Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.

Nature Neuroscience
|February 22, 2024
PubMed

Insights

Blood-brain barrier disruption occurs in COVID-19 and long COVID brain fog. This involves systemic inflammation and impaired immune responses, contributing to cognitive impairment.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Coronavirus disease 2019 (COVID-19) pathogenesis involves vascular disruption.
  • Neurological sequelae of long COVID are common, but blood-brain barrier (BBB) function in these conditions is not well understood.

Purpose of the Study:

  • To investigate the impact of COVID-19 and long COVID on blood-brain barrier (BBB) integrity.
  • To identify the mechanisms underlying cognitive impairment (brain fog) in long COVID.

Main Methods:

  • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess BBB permeability.
  • Transcriptomic analysis of peripheral blood mononuclear cells (PBMCs).
  • In vitro assays examining PBMC adhesion to brain endothelial cells and endothelial cell responses to patient serum.

Main Results:

  • Evidence of BBB disruption in acute COVID-19 and in long COVID patients with brain fog.
  • Transcriptomic analysis revealed coagulation system dysregulation and a weakened adaptive immune response in individuals with brain fog.
  • Increased PBMC adhesion to brain endothelial cells and inflammatory marker expression in endothelial cells exposed to long COVID serum.

Conclusions:

  • Sustained systemic inflammation and localized BBB dysfunction are key features of long COVID-associated brain fog.
  • These findings highlight the role of vascular and immune dysregulation in long COVID neurological symptoms.

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