Summary: Researchers comparing people with long COVID to those who fully recovered found that individuals reporting persistent cognitive symptoms such as brain fog display signs of increased brain inflammation and a reduced biological capacity to respond to stress. The study identified lower levels of nerve growth factor and higher levels of inflammatory markers in the long COVID group.
Although standard cognitive testing showed largely similar results between groups, people with long COVID reported worse overall quality of life, poorer physical and emotional health, and demonstrated specific deficits in verbal fluency. These objective biomarker differences provide biological validation for the symptoms many long COVID patients describe and point to potential targets for earlier diagnosis and tailored treatment.
Key Facts:
- Biomarker Imbalance: The long COVID group had reduced serum nerve growth factor and elevated interleukin-10 (IL-10), suggesting impaired neuroplasticity alongside increased inflammation.
- Language Deficits: Participants with long COVID scored worse on letter fluency tasks, indicating difficulty with rapidly retrieving words based on initial letters.
- Lower Quality of Life: People with long COVID reported significantly poorer physical well-being, emotional functioning, and overall psychological health compared with fully recovered controls.
Source: Corewell Health
New controlled research comparing inflammation and stress-response markers in people with long COVID versus fully recovered individuals reveals biological differences linked to persistent cognitive complaints.
Previous laboratory studies in animals had suggested that infection could alter brain inflammation and stress systems, but this is among the first controlled investigations to measure these markers in documented COVID-positive patients and directly compare those with lingering cognitive symptoms to those who recovered without ongoing issues.
Clinicians have struggled to explain why some patients develop long-term cognitive symptoms after COVID while others recover fully. Recent estimates suggest that millions worldwide continue to experience lingering effects of infection years after their initial illness, and this study aims to shed light on biological processes that may underlie those persistent complaints.
“We compared our long COVID participants to our healthy, fully recovered control group using neurocognitive testing, assessments of emotional functioning, quality-of-life measures, and blood markers related to the stress response,” said Michael Lawrence, Ph.D., a neuropsychologist at Corewell Health in Grand Rapids, Michigan and lead author of the study.
“To our knowledge, this is the first controlled clinical study demonstrating specific self-reported neurocognitive and central nervous system changes in long COVID patients, providing objective evidence that aligns with the symptoms patients report.”
The pilot study, published in PLOS One, included 17 confirmed COVID-19 patients—10 with long COVID symptoms and seven who had fully recovered with no lingering problems. The main findings included the following:
- Serum nerve growth factor, a protein that supports the brain’s ability to form new connections and adapt (neuroplasticity), was significantly lower in the long COVID group. That same group was more likely to show elevated interleukin-10 (IL-10), an immune marker associated with inflammation.
- On most neuropsychological tests the two groups performed similarly; however, people with long COVID scored significantly lower on letter fluency tasks, reflecting difficulties with rapid language retrieval and verbal processing.
- Participants with long COVID reported significantly worse outcomes on measures of quality of life, physical health, emotional functioning, and psychological well-being compared to fully recovered controls.
“Although this is a small pilot study and further research is needed, these results suggest clinicians could use biomarker and symptom assessments to identify struggling patients earlier and offer coordinated care,” said Judith Arnetz, Ph.D., professor emerita at Michigan State University College of Human Medicine and corresponding author on the study.
The investigators note a common clinical challenge: many patients with long COVID look normal on routine paper-and-pencil tests, which can lead to their symptoms being underestimated by family, employers, and even health care providers.
“Patients often report frustration when standard tests fail to capture their daily struggles,” Dr. Lawrence said. “Objective blood-based biomarkers combined with targeted assessments may help validate patients’ experiences and guide more personalized treatment.”
Both authors suggest a multidisciplinary approach could improve outcomes for patients with long COVID. Assessing inflammatory and neural biomarkers, and offering services such as speech therapy, stress-reduction psychotherapy, and treatments aimed at fatigue and cognitive fog may form components of an effective care plan.
About this long COVID and neurology research news
Author: Sarina Gleason
Source: Corewell Health
Contact: Sarina Gleason – Corewell Health
Image: The image is credited to Neuroscience News
Original Research: The findings will appear in PLOS One