A new brain imaging study led by scientists at the Center for Addiction and Mental Health (CAMH) has uncovered what researchers describe as the strongest evidence yet that long COVID is associated with damage to dopamine-releasing neurons in the brain. Published in eBioMedicineThe findings could help explain persistent problems such as fatigue-related loss of motivation, slower movements and memory difficulties. They may also point to new treatment strategies.
Long COVID is estimated to affect about five per cent of the world’s population, including about two million people in Canada. The condition can involve a wide 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. As widespread and disruptive as COVID can be, there are currently no evidence-based treatments, in part because scientists still don’t fully understand what happens 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 within 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 in healthy participants.
The researchers found substantially lower levels of this marker in people with long COVID in all major areas of the striatum. The striatum is a group of brain regions that helps regulate motivation, movement, and thinking. Lower levels of markers suggest reduced density of dopamine nerve terminals.
Different patterns of marker loss were also associated with different symptoms. Lower levels in the ventral striatum were related to greater loss of motivation. Reductions in the dorsal putamen were associated with slower movement, while lower levels in the caudate putamen were related to 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. “It is well known that this type of injury produces symptoms such as lack of motivation and motor slowing, and can contribute to memory difficulties in other neurological conditions. Our results suggest that a similar process is occurring in long COVID.”
Previous research pointed to brain inflammation
The new findings build on previous work from the same research team showing that people with long COVID have unusually high levels of inflammation in the brain. That inflammation seemed to be especially pronounced in regions that contained a large number of dopamine-releasing neurons.
“We know that inflammation can damage dopamine neurons. While our previous 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.
Together, the two studies suggest a possible connection between persistent brain inflammation and damage affecting the dopamine system.
A new direction for long COVID treatment
The results could change the way researchers approach the biology and treatment of long COVID. Much of the previous research has focused on inflammation in the brain and changes in immune activity. In 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 drugs that increase 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 may be difficult to measure from the outside.
“For five years I have been searching for answers about what happened to me after contracting COVID in 2021,” says Susan Deuville, Dr. Meyer’s lived experience research advisor. “It was a crushing loss of the life I had and the person I was before. Dr. Meyer’s research 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
Based on these results, researchers plan to begin a clinical trial in the coming months that will focus on dopamine function in people with long COVID. The objective will be to determine if modifying dopamine activity can improve memory, motivation and fatigue.
The trial will be carried out in collaboration with University Health Network (UHN), as part of a partnership between the hospitals aimed at closing the gap between physical and mental health care.
The study was supported by the Canadian Institutes of Health Research (CIHR).