Study Reveals Underlying Causes of COVID-19-Related Brain Fog

Neurological symptoms have been widely observed in COVID-19 patients, with many survivors exhibiting persistent neurological and cognitive impairment. New research from the University of Minnesota found that COVID-19 triggers inflammation in the brain, which is linked to many COVID-related symptoms such as fatigue and “brain fog.”

Published in Frontiers in Microbiology, the researchers examined the specific ways the virus impacts the brain, developing a preclinical model to accurately mimic the effects of COVID-19 on humans to explore the impact of age and sex on the brain-related impacts of the disease.

The study was led by Maxim Cheeran in the College of Veterinary Medicine, Ling Li in the College of Pharmacy and Walter Low in the Medical School. The findings include:

• SARS-CoV-2 infection triggered a neuroinflammatory response, despite the lack of detectable virus in the brain.
• Older age males showed a higher viral load and more pronounced symptoms.
• Older age also led to increased neurological inflammation.

The researchers also found several biological pathways that the virus impacts in the brain, including overactive or misdirected immune response, disruption to the protective blood-brain barrier, damage to cells lining blood vessels, and impacts to how nerve cells are formed and function. These impacts can impair brain function and may even lead to permanent damage.

“There are still things we don’t know about how coronavirus infection affects the brain, and our research is beginning to unravel the mystery,” said Cheeran. “We now know that viral infection in the lungs can cause inflammatory changes in the brain, affected by the age and sex of the patient. With this model, we can further examine the connections between the infected lung and the brain, and start development on targeted treatments to mitigate the impact of COVID-19 on the brain.”

In addition to new targeted therapies, these findings allow for more accurate vaccine development and continued research. The research team has a study underway that could shed light on the persistence of these symptoms in individuals experiencing long COVID, including the long-term impacts on neurocognitive behavior and memory loss.

This work was supported in part by grants from the National Institutes of Health/National Institute on Aging and the SURRGE award program of the University of Minnesota’s College of Pharmacy.