Biomarkers.

Area of Science:

• Neuroscience
• Immunology
• Infectious Diseases

Background:

• Mechanisms of post-COVID-19 cognitive impairment remain unclear.
• Increased blood-brain barrier (BBB) permeability and immune alterations are suspected contributors.
• Brain fog, characterized by memory loss and concentration difficulties, affects many post-SARS-CoV-2 patients.

Purpose of the Study:

• To investigate potential biological mechanisms underlying post-COVID-19 brain fog.
• To compare plasma biomarkers of inflammation, BBB disruption, and tau pathology in patients with and without brain fog.
• To identify differences in biomarkers between COVID-19 patients with and without cognitive impairment.

Main Methods:

• Cross-sectional study comparing COVID-19 positive (COV+) and negative (COV-) patients.
• Defined brain fog as persistent cognitive symptoms (>1 month) post-SARS-CoV-2 infection.
• Measured plasma cytokines, BBB markers (e.g., heparin-binding epidermal growth factor), and phosphorylated tau (pTau) using Simoa technology.
• Assessed cognitive function via neuropsychiatric testing and physician consensus diagnosis (NACC criteria).

Main Results:

• Lower levels of several cytokines (TNF-a, IL-4, IL-10, IL-22) were observed in patients with brain fog.
• Increased markers of BBB permeability (heparin-binding epidermal growth factor, vascular endothelial growth factor, placental growth factor) were found in brain fog patients.
• COVID-19 patients with mild cognitive impairment (MCI) showed lower TNF-a and higher pTau-217 (in Alzheimer's cases) compared to cognitively normal individuals.

Conclusions:

• Findings suggest immune exhaustion and increased BBB permeability as potential mechanisms for post-COVID-19 brain fog.
• Altered tau pathology markers indicate disrupted tau processing may also contribute to cognitive deficits.
• Biomarker analysis provides insights into the pathophysiology of neurological sequelae following SARS-CoV-2 infection.