Scientists uncover biological cause of Long COVID brain fog in major breakthrough

Scientists in Japan have identified a potential biological cause of Long COVID brain fog, providing evidence that the condition is more than just a lingering symptom and that it’s a measurable, molecular disorder in the brain.

A team at Yokohama City University led by Professor Takuya Takahashi found that people with Long COVID experience widespread increases in AMPA receptor activity, a type of molecule crucial for learning and memory.

“By applying our newly developed AMPA receptor PET imaging technology, we aim to provide a novel perspective and innovative solutions to the pressing medical challenge that is Long COVID,” said Professor Takahashi.

What is Long Covid brain fog?

Brain fog - a catch-all term for cognitive impairment, poor memory and sluggish thinking - is one of the most common and disabling symptoms of the SARS-CoV-2 infection (COVID-19).

Studies suggest it affects more than 80 per cent of people with Long COVID, leaving millions struggling to work, study or manage daily life.

Until now, scientists have struggled to find clear biological markers explaining why. Previous imaging studies showed subtle structural changes in the brain, but none could pinpoint the molecular disruptions responsible for the fog.

According to the World Health Organization, approximately six in every 100 people who have COVID-19 develop post COVID-19 condition.

How was the research carried out?

The Japanese team believed that AMPA receptors (AMPARs) might be involved. These receptors act as key communication hubs between brain cells and have previously been implicated in mental health and neurological conditions such as depression, schizophrenia and dementia.

Using a new technique called K-2 AMPAR PET imaging, the researchers scanned the brains of 30 Long COVID patients and compared the results with 80 healthy volunteers.

They found that receptor density was significantly elevated in patients - and the higher the AMPAR activity, the worse their cognitive symptoms.

Inflammation also appeared to play a role. Higher levels of inflammatory markers were linked to the same receptor increases, suggesting that the brain’s immune response may be driving the molecular changes.

“Our findings clearly demonstrate that Long COVID brain fog should be recognized as a legitimate clinical condition. This could encourage the healthcare industry to accelerate the development of diagnostic and therapeutic approaches for this disorder,” explains Takahashi.

While the work is still in its early stages, the findings could help. point toward treatments that reduce excessive AMPAR activity, potentially easing symptoms for those affected.