brain scan
© CC0/Public DomainBrain Scan
A new brain imaging study led by researchers at the Center for Addiction and Mental Health (CAMH), published in eBioMedicine, provides the strongest evidence to date that long COVID is associated with injury to dopamine-releasing neurons in the brain — a finding that may explain symptoms such as lack of motivation due to fatigue, slowed movement and memory difficulties, and could open the door to new treatment strategies.

Long COVID is estimated to affect 5% of the world's population and is characterized 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.

Brain scans point to dopamine loss

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 with healthy individuals. Specifically, lower markers in the ventral striatum were associated with 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.

Dr. Jeffrey Meyer, senior scientist at the Brain Health Imaging Center, Canada Research Chair, and senior author of the study, says:
"Our findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons. 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.

Meyer explains:
"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."
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.

Meyer adds:
"These results indicate that long COVID is, at least in part, a disorder of the brain's dopamine system. 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."
Hope and a trial ahead

For individuals affected by long COVID, the new findings offer hope.

Susan Deuville, lived experience research adviser to Meyer, said:
"For five years I have been seeking answers about what happened to me after I contracted COVID in 2021. It was a crushing loss of the life I had and the person I was before. Meyer's research 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 next 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.