A new imaging study reports a link between long COVID dopamine system changes and lingering symptoms such as fatigue, slowed movement, and memory issues. Led by scientists at the Centre for Addiction and Mental Health (CAMH) and published in eBioMedicine, the research provides what investigators describe as the strongest evidence to date that the condition is associated with injury to dopamine-releasing neurons. The findings may guide future treatments.
Long COVID is estimated to affect about five percent of the global population, including roughly two million people in Canada. The condition spans a broad range of symptoms persisting at least three months after infection. Brain-related complaints often include fatigue, brain fog, memory problems, and low mood. Despite its scale and impact, there are no evidence-based treatments, in part because the underlying brain changes remain unclear.
Long COVID dopamine changes seen on PET scans
For the study, researchers used positron emission tomography, or PET, to measure a well-established marker of dopamine neuron health in people with long COVID, then compared results with healthy participants.
They observed substantially lower levels of this marker across all major areas of the striatum, a set of brain regions that regulate motivation, movement, and aspects of cognition. Lower levels indicate reduced density of dopamine nerve terminals.
Patterns of marker loss tracked with specific symptoms. Lower levels in the ventral striatum correlated with greater loss of motivation. Reductions in the dorsal putamen were associated with slower movement. Lower levels in the caudate putamen were linked to memory difficulties.
“Our findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons,” said Dr. Jeffrey Meyer, Senior Scientist at the Brain Health Imaging Centre, Canada Research Chair, and senior author. He noted that such injury is known to cause lack of motivation and motor slowing, and may contribute to memory problems. “Our results suggest a similar process is occurring in long COVID.”
Earlier work suggested inflammation
The results build on prior research by the same team showing unusually high levels of brain inflammation in people with long COVID, especially in regions rich in dopamine-releasing neurons.
According to Dr. Meyer, inflammation can injure dopamine neurons. The new findings provide direct evidence that the dopamine neuron marker is reduced in those regions and that the loss aligns with patients’ symptoms. Together, the studies suggest a possible link between persistent brain inflammation and damage within the dopamine system.
A path toward targeted treatment
The findings could shift how researchers approach the biology and treatment of long COVID. While much previous work has centered on neuroinflammation and immune changes, few clinical trials have targeted dopamine-releasing neurons directly.
“These results indicate that long COVID is, at least in part, a disorder of the brain’s dopamine system,” Dr. Meyer said. He added that repurposing medications that augment dopamine function, including dopamine precursors and inhibitors of dopamine metabolism, could be a promising avenue.
For people living with long COVID, the study offers a potential biological explanation for symptoms that can be hard to quantify. Related research on neurological disease mechanisms, such as studies where mice are given brain organoids to study human neural development, is helping scientists map how changes in brain cells translate into behavior and cognition.
“For five years I have been seeking answers on what happened to me after I contracted COVID in 2021,” said Susan Deuville, a 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 to test dopamine-targeting approach
Building on the results, the team plans to launch a clinical trial in the coming months to target dopamine function in people with long COVID. The goal is to assess whether modifying dopamine activity can improve memory, motivation, and fatigue.
The trial will be conducted in collaboration with University Health Network as part of a partnership aimed at bridging mental and physical health care. The study was supported by the Canadian Institutes of Health Research.