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

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.