MSU, Corewell Health scientists find link between brain fog and long COVID

May 19, 2025

A new study that is the first to compare inflammation and stress responses in long COVID-19 patients with individuals who have fully recovered shows that those with continued brain fog and other cognitive issues have higher levels of stress hormones and inflammatory markers in their brains. While previous long COVID studies have shown an elevation in these markers in mice, this study evaluated the infection’s impact on the brain’s serum levels in documented COVID-positive patients.

Up until now, physicians have found it difficult to understand why certain patients develop post-COVID cognitive symptoms while others do not. Recent studies estimate tens of millions of people worldwide still have not recovered from the COVID infection, even five years later.

PLOS One recently published the work of lead author Michael Lawrence, PhD, neuropsychologist at Corewell Health, and MSU College of Human Medicine coauthors Bengt Arnetz, MD, PhD, Judith Arnetz, PhD, MPH, both professors emerita in the Department of Family Medicine, and Scott Counts, PhD, associate professor in the Departments of Family Medicine and Translational Neuroscience.

“We compared our long COVID participants to our healthy, fully recovered control group based on neurocognitive measures, emotional functioning, measures of quality of life as well as specific changes in blood markers assessing stress response,” said Lawrence. “To our knowledge, this is the first well-controlled study that shows specific self-reported neurocognitive and central nervous systems changes in long COVID patients which validates the symptoms they’ve been experiencing.”

The pilot study included 17 confirmed COVID patients (10 with long COVID and seven who were fully recovered with no lingering symptoms) and found the following:

Serum levels of nerve growth factor, a biomarker of the brain’s ability to change and adapt by forming new connections, were significantly lower in the long COVID group. This group was also more likely to have higher serum levels of interleukin (IL)-10, a marker of inflammation.

While there was virtually no difference between groups related to neuropsychological test outcomes, long COVID participants did score significantly lower on letter fluency, meaning they had more difficulty with quickly and accurately accessing language centers in the brain and producing words beginning with various letters.

The long COVID group also had significantly lower than healthy controls on quality of life, physical health, emotional functioning and psychological well-being responses.

“Although this is a smaller study and more work needs to be done, from a clinical application standpoint, physicians potentially can identify individuals who are struggling sooner and provide wrap-around care that could be helpful to them,” said Judith Arnetz.

According to the study authors, the struggle physicians have with identifying long COVID patients is that when asked to complete various written diagnostic tests, they tend to look normal. 

“These patients experience significant frustration, and their symptoms often may be minimized by friends, family and even the medical community,” Lawrence said. “It’s tough when everything looks normal on paper, but our patients continue to struggle and report a multitude of difficulties.”  

Arnetz agreed and indicated that physicians might want to take a multidisciplinary approach to care and assess inflammatory and brain biomarkers, which could ultimately offer a better path forward in treating patients with long COVID.

“Additional services such as speech therapy, psychotherapy for stress reduction and incorporating medications that target fatigue and mental fogginess could all be elements of creating a successful treatment plan as well,” Lawrence said.

Media Contacts

Emily Linnert | Michigan State University

Sarina Gleason | Corewell Health

Story originally published by Corewell Health