To investigate whether the brain’s dopamine system is involved, the researchers used PET imaging to measure a well-established marker of dopamine neuron integrity in individuals with long COVID and healthy control participants.
The reduced signal indicates a loss of dopamine nerve terminal density, providing direct evidence that dopamine-releasing neurons are injured in long COVID.
The pattern suggests that damage within specific regions of the dopamine system may contribute to distinct neurological symptoms experienced by people with long COVID.
The study also shifts attention beyond inflammation alone and suggests that long COVID should be considered, at least in part, a disorder affecting the brain’s dopamine system.
The researchers suggest that repurposing dopamine precursors or drugs that inhibit dopamine metabolism could represent a promising strategy for treating persistent cognitive and neurological symptoms associated with long COVID.
New brain imaging research has provided the strongest evidence to date that long COVID is associated with injury to the brain’s dopamine system, offering a potential biological explanation for persistent symptoms such as fatigue, slowed movement, lack of motivation, and memory problems.
The study, published in eBioMedicine by researchers at the Centre for Addiction and Mental Health in Canada, used positron emission tomography (PET) imaging to examine dopamine-releasing neurons in people with long COVID. The findings suggest that reduced dopamine nerve terminal density in key brain regions may underlie many of the neurological symptoms experienced by patients and identify a potential therapeutic target for future treatments.
Long COVID is estimated to affect approximately nine million adults in the United States and about 5% of the global population, making it one of the most common chronic conditions to emerge from the COVID-19 pandemic. The condition is characterized by symptoms that persist for at least three months after the initial SARS-CoV-2 infection and commonly includes fatigue, brain fog, memory impairment, and mood changes. Despite its prevalence, there are currently no evidence-based treatments, largely because the biological mechanisms driving these symptoms remain poorly understood.
To investigate whether the brain’s dopamine system is involved, the researchers used PET imaging to measure a well-established marker of dopamine neuron integrity in individuals with long COVID and healthy control participants.
Compared with healthy volunteers, participants with long COVID had significantly lower levels of the dopamine neuron marker throughout the striatum, a brain region that plays a central role in motivation, movement, learning, and cognition. The reduced signal indicates a loss of dopamine nerve terminal density, providing direct evidence that dopamine-releasing neurons are injured in long COVID.
The imaging findings also closely matched patients’ clinical symptoms. Lower dopamine markers in the ventral striatum were associated with greater loss of motivation, reductions in the dorsal putamen correlated with slower movement, and lower marker levels in the caudate were linked to poorer memory performance. The pattern suggests that damage within specific regions of the dopamine system may contribute to distinct neurological symptoms experienced by people with long COVID.
The findings build on the research group’s earlier work demonstrating elevated inflammation in the brains of people with long COVID, particularly in regions rich in dopamine-producing neurons. Because inflammation is known to damage dopamine neurons in other neurological disorders, the new study provides direct evidence that this inflammatory process may be accompanied by measurable injury to the brain’s dopamine system. The close relationship between dopamine neuron loss and symptom severity further strengthens the case that dopamine dysfunction plays a central role in the condition.
The study also shifts attention beyond inflammation alone and suggests that long COVID should be considered, at least in part, a disorder affecting the brain’s dopamine system. That conclusion has important therapeutic implications because several medications already approved for other neurological disorders increase dopamine availability or enhance dopamine signaling. The researchers suggest that repurposing dopamine precursors or drugs that inhibit dopamine metabolism could represent a promising strategy for treating persistent cognitive and neurological symptoms associated with long COVID.
The findings also provide biological evidence supporting the experiences of people living with long COVID, many of whom have struggled for years with debilitating symptoms despite the absence of clear diagnostic markers. By demonstrating measurable injury to dopamine-releasing neurons, the study offers objective evidence that persistent neurological symptoms have a biological basis.
Building on these results, the investigators plan to launch a clinical trial in collaboration with University Health Network to evaluate whether therapies that improve dopamine function can reduce fatigue, improve motivation, and enhance memory in people with long COVID. If successful, the trial could pave the way for one of the first mechanism-based treatment approaches for the condition.
