Long COVID may be damaging your brain's Dopamine system, groundbreaking study finds

Long COVID is estimated to affect five per cent of the world population, including two million Canadians, and is characterised by a wide range of persistent and sometimes debilitating symptoms, including brain-related ones such as fatigue, brain fog, memory problems, or low mood, that continue for at least three months following the initial COVID-19 infection. Despite its prevalence, no evidence-based treatments currently exist, largely due to limited understanding of the underlying brain pathology.

In the new study, researchers used positron emission tomography (PET) brain imaging to measure a well-established marker of dopamine neuron integrity in people with long COVID and healthy individuals.

The team found significantly lower levels of the imaging marker—indicating reduced dopamine nerve terminal density—across all major regions of the striatum, the brain structure that plays a central role in motivation, movement, and thinking, in people with long COVID compared to healthy individuals. Specifically, lower markers in the ventral striatum were associated with a greater loss of motivation, marker reductions in the dorsal putamen were associated with slowed movement speed, and marker loss in the caudate putamen was linked 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. “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.”

Building on earlier evidence

The findings build on the team’s earlier work showing that people with long COVID have elevated levels of inflammation in the brain, especially in regions that are rich in 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.

Implications for treatment

The study represents a notable shift in how long COVID may be understood and treated. Previous studies predominantly focused on brain inflammation and immune changes that occur during long COVID, with almost no clinical trials targeting the 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 individuals affected by long COVID, the new findings offer hope.

“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.”

Based on the new findings, the team plans to launch a clinical trial targeting dopamine function to help with memory, motivation, and fatigue in people with long COVID in the upcoming couple of months, in collaboration with University Health Network (UHN), as part of the hospitals’ partnership to help bridge the gap between mental and physical health care.

The study was supported by the Canadian Institutes of Health Research (CIHR). Graduate student Yuhan Liu was the first author of the study.