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Long COVID Brain Fog “Very Well Explained” By Altered Levels Of 2 Key Biomarkers

May 16, 2025 by Deborah Bloomfield

Brain fog has become one of the most familiar, and most feared, symptoms associated with long COVID. In a new study, scientists say they’ve identified two biomarkers that are altered in people with long COVID compared with people who recovered fully from the infection, indicating that there may be more we can do to identify and support patients earlier. 

Since the opening stages of the pandemic five years ago, it’s been clear that some people experience lingering symptoms after their initial COVID-19 infection. In many cases, these were people who had had mild initial symptoms, had not been hospitalized, and who had previously been fit and healthy. 

The road to understanding and developing treatments for this condition has been long, and research is still continuing. Meanwhile, patients report difficulties in convincing medical professionals that their symptoms – which can be wide-ranging and hugely variable – are real.

Many of these individuals six months out are still left feeling as if they’re not understood and they’re not receiving care.

Dr Michael Lawrence

“Individuals that experience long COVID report a constellation of symptoms, and these symptoms can be cognitive, they can be physical, and they can be emotional,” study first author Dr Michael Lawrence, from Corewell Health in Grand Rapids, Michigan, told reporters at a recent press briefing. 

“[We can estimate] around 3-4 percent of all Americans will be suffering from brain fog and the symptoms,” added co-author Dr Bengt Arnetz. “So, it’s quite a substantial number of people.”

There have been some hopeful breakthroughs, but one key area of study revolves around identification. What separates people who recover fully from COVID from those who don’t, and could we find and start treating these people at an earlier stage?

That was the driving force behind the new pilot study from Lawrence, Arnetz, and colleagues. 

“If we can identify these individuals based upon these biomarkers that may be vulnerable to experiencing long COVID, then we can wrap care around them early and hopefully affect change soon, because many of these individuals six months out are still left feeling as if they’re not understood and they’re not receiving care,” said Lawrence.

The team recruited 17 patients with a history of COVID-19 confirmed with a positive PCR test. Within this cohort, 10 people had long COVID, while the other seven had fully recovered. 

“I think one of the things that makes our study very unique is that we had PCR-confirmed COVID patients,” Lawrence explained. “And we defined long COVID much more conservatively than other literature. Other literature says that you have to have persisting symptoms for greater than three months. In our study, we actually made it greater than six months.”

As well as answering questions about their symptoms and quality of life, the participants underwent tests of cognitive functions – covering things like attention, memory, and processing speed – and the researchers took samples of their blood and plasma to analyze. 

The key finding was that serum levels of a protein called nerve growth factor were significantly lower in the long COVID group. At the same time, this group had higher serum levels of interleukin-10 (IL-10).

Arnetz explained that nerve growth factor works in the brain by stimulating neurons to grow and connect with one another, while IL-10 is a marker of inflammation. It’s both part of the way the body fights inflammation, and part of a mechanism that works to drive energy in the body. 

Taken together, the team believes that low nerve growth factor could be impacting brain plasticity, explaining cognitive symptoms like brain fog, while increased IL-10 could be a sign of ongoing inflammation as well as a sign of the body trying to combat fatigue.

“Every time we learn new things, our brain changes,” Lawrence elaborated. “What we hear from COVID patients is, ‘I can still do things, but everything takes more energy. Everything’s harder. Nothing’s as automatic as it used to be’.”

“Those symptoms I think are very well explained by what [Arnetz] knows about these biomarkers.”

Lawrence explained that one of the frustrating things for long COVID patients is that their neurocognitive test results can often come back normal, while they themselves know that they feel different. There’s also no concrete way of measuring fatigue. That’s why finding objective biomarkers like this could be so helpful for this patient group – and potentially for others too. 

“Probably the biggest parallel from a medical diagnosis is fibromyalgia, and individuals with fibromyalgia describe a lot of what they call ‘fibro fog’, which is very similar to the fogginess that post-COVID patients experience as well. And so I think looking at a fibromyalgia population and comparing these biomarkers would be very interesting as well,” Lawrence said in response to IFLScience’s question on the topic.

This study was intentionally small, but the team would like to see things scaled-up in the future, as well as tracking patients to see how levels of biomarkers might change over time. 

“I think if we can identify these individuals early with biomarkers, then we can develop multidisciplinary treatment to focus on all aspects of the individual,” Lawrence concluded.

“We really need to treat the whole person, but we need to treat it early.”

The study is published in the journal PLOS One. 

Deborah Bloomfield
Deborah Bloomfield

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Source Link: Long COVID Brain Fog “Very Well Explained” By Altered Levels Of 2 Key Biomarkers

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