What is the link between Long Covid and The Mysterious Brain Fog?

Highlights:

• AMPAR receptors may explain the onset of brain fog among those affected by long Covid
• AMPARs also provide explanation for receptor expression triggers as a result of inflammation
  

Despite many years having passed since the COVID-19 pandemic first struck, the full extent of the harm caused by SARS-CoV-2 has never been fully understood. Cognitive impairment in the form of brain fog, which occurs as a result of COVID-19 infection, is one of the most debilitating in this regard and is found to occur among 80% of those affected by Long Covid.

Previous studies have shown changes occurring in brain structure, but the molecular dysfunctions could not be deciphered. Objective biomarkers could not be devised to confirm Long COVID diagnosis and formulate treatments until the breakthrough research by Professor Takuya Takahashi, which was published in Brain Communications on October 1, 2025.

Drawing upon findings from research on psychiatric and neurological disorders, including schizophrenia, dementia, depression, and bipolar disorder, the team made the conjecture that patients with brain fog had damaged or dysfunctional AMPA receptors, which are the molecules designated for memory and learning.

The researchers used a novel method, referred to as the [11C]K-2 AMPAR PET imaging, to determine the density of AMPARs in the human brain. Imaging data from 30 patients with Long Covid was compared to that of 80 healthy individuals, and revealed variations in the density of AMPARs in the brains of patients in line with the understanding that heightened receptor density was proportionate to the severity of impairment.

Alongside, AMPAR levels were also associated with the proportions of inflammatory markers, pointing toward receptor expression getting triggered in the face of inflammation.

The research findings represent a resounding moment in the treatment of Long Covid. The role of AMPARs offers a biological explanation for cognitive decline and opens the doors for new opportunities to treat the disease. For example, drugs can be devised to derail AMPAR activity, thereby helping keep a check on brain fog.

Prof. Takahashi added that Long Covid brain fog should be considered as a legitimate clinical condition, with his team’s findings helping us better understand and mitigate threats posed by the disease.