Long COVID may affect the brain’s dopamine system

Long COVID is estimated to affect about 5% of the world’s population, including approximately 2 million people in Canada. The condition can involve a wide range of symptoms lasting at least three months after the initial COVID-19 infection.

Common brain-related symptoms include fatigue, brain fog, memory problems and low mood. Despite the condition’s widespread and potentially long-lasting effects, there are currently no evidence-based treatments, partly because researchers do not yet fully understand what happens in the brain.

PET brain scans reveal changes in dopamine-related regions

For the new study, researchers used positron emission tomography (PET), an imaging technique that measures biological activity in the brain. They examined established markers associated with the health and integrity of dopamine neurons in people with long COVID and compared the results with those of healthy participants.

Researchers found that marker levels were significantly lower in all major regions of the striatum among people with long COVID. The striatum is a group of brain regions involved in motivation, movement and thinking. Lower marker levels suggest a decreased density of dopaminergic nerve endings.

Different patterns of marker loss were associated with different symptoms. Lower levels in the ventral striatum were linked to a greater loss of motivation. Reduced levels in the dorsal putamen were associated with slowed movement, while decreased levels in the caudate putamen were associated with memory impairment.

“Our findings provide strong evidence that long-term infection with COVID-19 is accompanied by the loss of dopamine-releasing neurons,” said Dr. Jeffrey Meyer, senior scientist at the Center for Brain Health Imaging, Canada Research Chair and lead author of the study.

“This type of damage is well known to cause symptoms such as lack of motivation and reduced motor skills, and may contribute to memory impairment in other neurological conditions. Our results suggest that a similar process is occurring during long-term COVID-19 infection.”

Previous research linked long COVID to brain inflammation

The new findings build on previous work by the same research team, which showed unusually high levels of inflammation in the brains of people with long COVID. The inflammation appeared to be particularly pronounced in areas containing large numbers of dopamine-releasing neurons.

“We know that inflammation can damage dopamine neurons. While our previous studies showed high levels of inflammation in these regions, this study provides direct evidence that dopamine neuron markers are reduced in the same regions and that this reduction correlates with patient symptoms,” Dr. Meyer explained.

Together, the two studies suggest a possible link between persistent brain inflammation and damage involving the dopamine system.

Study may point to new long COVID treatment strategies

The results could change how researchers investigate the biology and treatment of long COVID. Much of the previous research has focused on inflammation and immune activation in the brain. By comparison, relatively few clinical trials have directly targeted dopamine-releasing neurons.

“These results indicate that long-term COVID-19 infection is, at least in part, a disorder of the brain’s dopamine system,” Dr. Meyer said. “This suggests that repurposing drugs that enhance the function of dopamine-releasing neurons, such as dopamine precursors or dopamine metabolism inhibitors, may be a promising approach.”

For people who have lived with long COVID for extended periods, the findings may also provide a biological explanation for symptoms that can be difficult to measure externally.

“For five years, I have been searching for answers to what happened to me after contracting the coronavirus in 2021,” said Susan Deville, Dr. Meyer’s real-life research advisor. “This has been a traumatic event that has cost me so much of my life and who I used to be. Dr. Meyer’s research brings me hope. It also proves what those who have been suffering from COVID-19 for so long have always known: COVID-19 is real and its effects are devastating.”

Clinical trials targeting dopamine function are planned

Based on these results, researchers plan to begin clinical trials targeting dopamine function in people with long COVID in the coming months. The goal is to determine whether modifying dopamine activity can improve memory, motivation and fatigue.

The trial is being conducted in collaboration with the University Health Network (UHN) as part of a partnership between hospitals aimed at bridging the gap between mental and physical health care.

This research was supported by the Canadian Institutes of Health Research (CIHR).