A new brain imaging study led by scientists at the Centre for Addiction and Mental Health (CAMH) has uncovered what researchers describe as the strongest evidence so far that long COVID is associated with damage to dopamine-releasing neurons in the brain. Published in eBioMedicine, the findings could help explain persistent problems such as fatigue-related loss of motivation, slower movement, and memory difficulties. They may also point toward new treatment strategies.
Long COVID is estimated to affect about five per cent of the global population, including roughly two million people in Canada. The condition can involve a broad range of symptoms that continue for at least three months after the initial COVID-19 infection. Common brain-related symptoms include fatigue, brain fog, memory problems, and low mood. Despite how widespread and disruptive long COVID can be, there are currently no evidence-based treatments, in part because scientists still do not fully understand what is happening in the brain.
Brain Scans Reveal Changes in the Dopamine System
For the new study, researchers used positron emission tomography (PET), an imaging technique that can measure biological activity inside the brain. They examined a well-established marker associated with the health and integrity of dopamine neurons in people with long COVID and compared the results with those from healthy participants.
The researchers found substantially lower levels of this marker in people with long COVID across all major areas of the striatum. The striatum is a group of brain regions that helps regulate motivation, movement, and thinking. Lower marker levels suggest a reduced density of dopamine nerve terminals.
Different patterns of marker loss were also associated with different symptoms. Lower levels in the ventral striatum were linked to greater loss of motivation. Reductions in the dorsal putamen were associated with slower movement, while lower levels in the caudate putamen were connected with memory difficulties.
“Our findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons,” says Dr. Jeffrey Meyer, Senior Scientist at the Brain Health Imaging Centre, Canada Research Chair, and senior author of the study. “This kind of injury is well known to produce symptoms like lack of motivation and motor slowing, and may contribute to memory difficulties in other neurological conditions. Our results suggest a similar process is occurring in long COVID.”
Earlier Research Pointed to Brain Inflammation
The new findings build on previous work by the same research team showing that people with long COVID have unusually high levels of inflammation in the brain. That inflammation appeared to be especially pronounced in regions containing large numbers of dopamine-releasing neurons.
“We know that inflammation can injure dopamine neurons. While our earlier research showed high levels of inflammation in those regions, this study provides direct evidence that the dopamine neuron marker is reduced in the same regions — and that this loss correlates with patients’ symptoms,” explains Dr. Meyer.
Taken together, the two studies suggest a possible connection between persistent brain inflammation and damage involving the dopamine system.
A New Direction for Long COVID Treatment
The results could change how researchers approach the biology and treatment of long COVID. Much of the previous research has centered on inflammation in the brain and changes in immune activity. By comparison, very few clinical trials have focused directly on dopamine-releasing neurons.
“These results indicate that long COVID is, at least in part, a disorder of the brain’s dopamine system,” adds Dr. Meyer. “This suggests that repurposing medications that augment the function of dopamine-releasing neurons, including dopamine precursors and inhibitors of dopamine metabolism, could be a promising approach.”
For people living with long COVID, the findings may also provide a biological explanation for symptoms that can be difficult to measure from the outside.
“For five years I have been seeking answers on what happened to me after I contracted COVID in 2021,” says Susan Deuville, lived experience research advisor to Dr. Meyer. “It was a crushing loss of the life I had and the person I was before. The research of Dr. Meyer brings hope. It also validates what long COVID sufferers have always known — long COVID is real and the effects are devastating.”
Clinical Trial Planned to Target Dopamine Function
Building on these results, the researchers plan to begin a clinical trial in the upcoming couple of months that will target dopamine function in people with long COVID. The goal will be to determine whether modifying dopamine activity can improve memory, motivation, and fatigue.
The trial will be conducted in collaboration with University Health Network (UHN), as part of a partnership between the hospitals aimed at bridging the gap between mental and physical health care.
The study was supported by the Canadian Institutes of Health Research (CIHR).
