Scientists May Have Discovered What Causes Long COVID Brain Fog

Scientists May Have Discovered What Causes Long COVID Brain Fog

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  • New study looks at brain scans of people with brain fog due to long COVID.

  • Researchers linked long COVID brain fog to leaky blood vessels in the brain.

  • Doctors say there are still limited treatments for brain fog due to long COVID.

Nearly 50% of people with long COVID experience brain fog, making it a common symptom of the condition. But the exact cause of long COVID brain fog has been a mystery. Now, a small study suggests this brain fog could be due to leaky blood vessels in the brain.

The small study, which was published in the journal Nature Neuroscience, analyzed blood samples—specifically, serum and plasma—from 76 patients who were hospitalized with COVID-19 in March or April 2020, along with those from 25 people taken before the pandemic. The researchers discovered that people who said they had brain fog had higher levels of a protein in their blood called S100β than people who didn’t have brain fog.

S100β is made by cells in the brain and isn’t normally found in the blood. That suggests that the patients had a breakdown in the blood-brain barrier, which blocks certain substances from getting to the brain and spinal cord, the researchers noted.

The scientists then did MRI scans with dye of 22 people with long COVID (11 of them who reported having brain fog), along with 10 people who recovered from COVID-19. They found that long COVID patients who had brain fog had signs of a leaky blood-brain barrier. Specifically, the dye injected into the bloodstream leaked into their brains and pooled in regions that play a role in language, memory, mood, and vision.

“Traditional imaging approaches haven’t shown any real sign of ‘damage’ in the brains of patients [with long COVID brain fog],” says study co-author Matthew Campbell, Ph.D., a genetics professor and head of genetics at Trinity College Dublin. “Our approach made use of a dye called a contrast agent as well as a special type of analysis to pinpoint blood vessel leakiness in distinct regions of the brain.”

What does this mean for long COVID patients with brain fog? Here’s what we know right now.

What is brain fog?

Brain fog is a term used to describe a range of neurocognitive symptoms that can include trouble with focus, concentration, and memory, according to the National Institutes of Health (NIH). That can lead to “an inability to perform effectively at work or in school or making a significant financial error,” says Scott Kaiser, M.D., a board-certified geriatrician and director of Geriatric Cognitive Health for the Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA.

But, the definition of brain fog is a little vague. “You can ask 10 patients and 10 healthcare providers and get literally 20 different answers,” says Jim Jackson, Psy.D., neuropsychologist and professor of medicine at Vanderbilt Medical Center and author of the book Clearing the Fog: From Surviving to Thriving with Long Covid—A Practical Guide.

Nizar Souayah, M.D., a neurology professor at Rutgers New Jersey Medical School, agrees. “You can ask patients to describe their brain fog, and they will have totally different answers,” he says.

Brain fog is listed by the Centers for Disease Control and Prevention (CDC) as one of the main symptoms of long-COVID, along with fatigue, chronic cough, and shortness of breath. But brain fog isn’t just related to COVID-19—lack of sleep, certain medications, and a poor diet can also contribute to brain fog.

What causes brain fog with long COVID?

This is still being explored, but science has uncovered a few things. In the latest study, people with long COVID brain fog had blood vessel leakage in areas of the brain that are involved in memory and attention, Campbell points out. “This leakiness likely disrupts the integrity of neurons in the brain by shifting the delicate balance of materials moving into and out of the brain,” he says. Cue the brain fog.

“This phenomenon—having a leaky blood-brain barrier—is a very common route through which cognitive impairment occurs in a wide array of diseases and syndromes,” Jackson says, listing off multiple sclerosis, sepsis, and major depression as a few examples.

Research published last year in the journal Cell also found a link between low levels of serotonin, a chemical that sends signals between nerve cells, and brain fog. For that study, researchers analyzed data from 1,540 people with symptoms of long COVID, as well as blood samples from 58 people who had brain fog between three and 22 months after they had COVID-19.

The researchers found that people who had recovered from COVID-19 but had brain fog had much lower levels of serotonin than people who were in the early stages of a COVID-19 infection and those who had no symptoms after recovering from COVID-19. The researchers pointed out that, while it’s normal for the body’s production of hormones and chemicals to be lower than usual during a viral infection, those levels usually bounce back—and serotonin was the only one that didn’t recover in patients with brain fog.

Overall, though, “there’s still a great deal of uncertainty” about what causes COVID-19 brain fog, Dr. Kaiser says.

What to do if you have long COVID brain fog

If you have brain fog and suspect it’s due to long COVID, Dr. Kaiser recommends contacting your healthcare provider. “There are now many specialty resources available to support people experiencing prolonged symptoms and there may be opportunities to better understand the nature of an individual’s cognitive dysfunction and tailored strategies to address this,” he says. However, Dr. Souayah points out that it can be difficult to get an appropriate diagnosis. “We don't have any good biomarkers for this,” he says.

Still, Dr. Kaiser says that lifestyle moves that can be good for overall brain health may also help, including:

  • Following an anti-inflammatory diet

  • Doing physical and cognitive exercises

  • Trying to get seven-plus hours of sleep at night

  • Having healthy social connections

  • Managing stress

  • Doing creative activities

“Some people may even benefit from a formal cognitive rehabilitation program,” Dr. Kaiser says. Jackson agrees. “We see many people with cognitive impairment after COVID make significant improvements over time with the help of cognitive rehabilitation,” he says. “It isn't a 'magic pill' but, for many, it is the treatment that allows them to function again.”

But Campbell notes that there are currently “limited treatments” for patients. “We do hope that drugs that have the potential to treat blood vessel damage might have utility,” he adds.

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