Small study shows a possible reason some long COVID patients experience 'brain fog'

According to a new study published in Nature Neuroscience, researchers at Trinity College in Ireland used blood tests to measure certain biological markers and specialized brain images to discover that long COVID patients with brain fog had more permeability or "leakiness" of their blood-brain barrier – offering the first biological evidence that this symptom may be due to underlying changes in the brain.

"A lot of long COVID symptoms, especially brain fog, are often written off as 'oh that’s all in your head' but this study is suggesting an actual biological mechanism behind it," Dr. Leah Croll, neurologist and assistant professor at Temple University, told ABC News. "Knowing this is real can be very validating for people who experience this symptom."

While this study is small, it could help inform ongoing research to better understand how to diagnose and treat long COVID that impacts millions of Americans. There is currently no test or treatment for this condition that can be disabling to those who have it.

In the study, researchers selected 32 patients who had COVID-19 in March or April of 2020 to undergo specialized brain imaging called a dynamic contrast-enhancing MRI – 10 had recovered from COVID-19, 11 had long COVID, and 11 had long COVID with brain fog. They found that the brain images showed more permeability or "leakiness" of the blood-brain barrier in patients who had long COVID with brain fog compared to the other groups. They also conducted cognitive tests and showed that six of the participants with brain fog had mild-to-moderate cognitive impairment and specifically showed problems with recall, executive functioning and word finding.

The researchers also measured blood markers of inflammation and blood clotting, and some markers related to the blood-brain barrier in 76 people who were hospitalized with an acute COVID-19 infection in March and April of 2020. It revealed that patients who specifically said they had brain fog with their acute infection had a statistically significant increase in a marker that is indirectly associated with blood-brain barrier dysfunction. Researchers say these findings suggests that inflammation impacting the blood-brain barrier may contribute to people experiencing brain fog with both acute and long COVID, but brain imaging was not done on the patients with an acute infection in the study.

There are limitations of the study. It was only done with a few people at one hospital in Ireland in the first stages of the COVID-19 pandemic before vaccines were available, so it may not be generalizable across all people who currently have long COVID, but it does provide new insights. More research is needed to confirm this finding and understand the implications of it, but experts say it may help researchers as better tests and treatments are developed for long COVID in the future.

"Right now, we're beginning to understand the biological underpinnings of COVID-related brain fog. Gaining that understanding is the vital first step we need to advance future research." Croll said. "I am hopeful that we are on a path towards effective tests and treatments, one study at a time."

Dr. Jade A Cobern, board-certified physician in pediatrics and preventive medicine, is a fellow of the ABC News Medical Unit.