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. 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.

“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 Center, 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.”

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.