New ‘long COVID' study zeroes in on possible biological cause of brain fog
St. PAUL, Minn., May 15 (UPI) -- Millions of "long COVID" patients coping with debilitating "brain fog" and chronic fatigue, who are looking for answers to what's at the root of their illness, received a hopeful sign through a new study released Thursday.
The answers, though somewhat complex, appear to be biological and neurological, authors of the study said. In other words, it's not just in patients' heads.
An estimated 12 million COVID "long-haulers" in the United States experience a range of neurological symptoms such as feeling slow, having difficulty thinking or concentrating, confusion and forgetfulness many months after recovery from the viral infection.
Sufferers have reported up to 200 different symptoms, both mental and physical, the most common of which include brain fog, lingering fatigue and shortness of breath.
The neurological symptoms, for example, can limit those who once exceled at sophisticated mental "multitasking" to doing just one thing at a time, making them far less able to handle stress or tap the mental flexibility needed for their jobs.
Since long COVID first emerged as a recognized syndrome, the hunt has been on to find a "biological mechanism" at the root of the malady. Those efforts got a boost this week with the publication of a small-scale study showing altered levels of a pair of key brain chemicals in patients who complained of symptoms six months after infection.
Researchers from Corewell Health in Grand Rapids, Mich., and Michigan State University said their findings provide more evidence that a biological mechanism is indeed at the root of the cognitive impairments.
The study is the first to directly measure inflammation in long COVID patients and bolsters theories that the pernicious brain fog and fatigue are not just mental issues, but linked to a biological cause that can be objectively assessed, the authors say.
More than 6% of American adults reported they were experiencing long COVID symptoms in 2023, translating to nearly 25 million people. Of those, about half have complained of brain fog -- and at those levels the need to understand and develop health strategies for them is tremendous.
The Michigan study, published in multidisciplinary journal PLOS One, looked for telltale biomarkers and to assess cognition in patients who have been very "conservatively" defined as having long COVID -- that is, those who were still experiencing brain fog six months after initial infection with the SARS-CoV-2 virus, the authors said.
They looked at a total of 17 people with confirmed COVID diagnoses, including 10 who were still reporting long COVID symptoms and a control group of seven others who had recovered without any long-lasting symptoms.
The authors found that those with the symptoms had lower serum levels of nerve growth factor, or NGF, a protein that plays a key role in neuron development and maintenance of the brain's plasticity. NGF is associated with high-level cognitive functions that require memory and mental flexibility.
Those same subjects also had higher levels of interleukin-10, a powerful anti-inflammatory protein secreted by white blood cells that plays a crucial role in regulating the immune system.
Meanwhile, the group also showed declines in "letter fluency," a neurological cognition test meant to measure how quickly subjects can perform "executive function" mental tasks requiring working memory and attention to detail.
According to study co-author Dr. Bengt Arnetz, a professor of family and preventive medicine and former chairman of Michigan State University's Department of Family Medicine Clinical Center, the combination of these biological and neurological differences in long COVID sufferers is significant.
"We found biological changes, which I think it's very big strength for this study," he told reporters during a virtual press conference earlier this week. "In parallel with the effects on executive function, we also saw that [NGF], which reflects the brain's ability to adapt to grow new neurons and connection, was suppressed in long COVID. This is aligned with the findings in the neuro-cognitive test.
"And that's a very novel finding. No one has really looked at that before [among patients] with proven COVID cases who have recovered from the infection."
Co-author Michael Lawrence, a clinical neuropsychologist with Corewell Health in Grand Rapids, said the long COVID sufferers underwent a battery of psychological exams to assess what effects the condition has had on their mental acuity. He found that, generally speaking, they "look normal on neurocognitive testing" -- except for one measure.
"Out of the multitude of tests that we gave, only one test seemed to show group differences, and that test is a test of what we call letter fluency. It measures executive functioning, but executive functioning under time constraints," he told UPI.
Long COVID patients come to his practice complaining of challenges relating to fatigue, brain fog and being "ineffective and inefficient," he said, but they are continually frustrated and often feel "invalidated" by the medical community because there was no known biological reason for their complaints.
The study results suggest "it's this processing speed-related issue that we think is somewhat related to COVID 'fog,' but also somewhat different, outside of the cognitive domain" -- thus likely pointing to a biological cause.
The deficit of interleukin-10, "given that it's an energy production protein... I think there is a relationship there," Lawrence said. "And I think it's helpful, because now we have some objective findings that really confirm what patients are describing and feeling."
The study provides hope that "if we can identify these individuals early with biomarkers, then we can develop multidisciplinary treatment to focus on all aspects of the individual," he added.
"I think patients and our medical community, at least years ago, tended to separate the mental health from the physical. But what we know is they're all very interconnected. The more we can improve mental health-related symptoms, what we see is decreased reports of pain and fatigue. We really need to treat the whole person, but we need to treat it early."
Future researchers "can look at these biomarkers over time to see what treatments tend to affect or change these serum levels," Lawrence said.
Copyright 2025 UPI News Corporation. All Rights Reserved.
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