A new brain‑imaging study led by researchers at the Centre for Addiction and Mental Health (CAMH) has uncovered what the team describes as the strongest evidence to date linking long COVID to damage of dopamine‑releasing neurons in the brain. The findings, published in *eBioMedicine*, may explain persistent symptoms such as fatigue‑related loss of motivation, slower movement, and memory challenges, and could point toward novel treatment approaches.
Long COVID is estimated to affect about five percent of the global population, including roughly two million people in Canada. The condition can involve a wide range of symptoms that persist for at least three months after the initial infection. Typical brain‑related manifestations include fatigue, brain fog, memory deficits, and low mood. Despite its prevalence and impact, evidence‑based treatments remain unavailable, partly because the underlying brain mechanisms are not yet fully understood.
Brain Scans Reveal Changes in the Dopamine System
The study employed positron emission tomography (PET), an imaging technique that quantifies biological activity within the brain. Researchers assessed a well‑validated marker of dopamine‑neuron health and integrity in individuals with long COVID and compared these measurements to those obtained from healthy control participants.
Participants with long COVID showed markedly lower marker levels across all major regions of the striatum—a brain structure that governs motivation, movement, and cognition. Reduced marker levels indicate a diminished density of dopamine‑containing nerve terminals.
The distribution of marker loss correlated with specific clinical features. Lower values in the ventral striatum corresponded to reduced motivation, while decreases in the dorsal putamen were linked to motor slowing. Losses in the caudate putamen were associated with memory impairment.
“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.”
Earlier Research Pointed to Brain Inflammation
These results build on earlier work by the same team, which demonstrated that individuals with long COVID exhibit unusually elevated brain inflammation, particularly in areas rich in dopamine‑releasing neurons.
Dr. Meyer notes, “We know that inflammation can damage dopamine neurons. While our prior research revealed high inflammation levels in these regions, the current study offers direct evidence that the dopamine‑neuron marker is reduced in the same areas, and that this loss aligns with patients’ symptom profiles.”
Collectively, the two investigations point to a potential link between ongoing brain inflammation and dopamine‑system injury.
A New Direction for Long COVID Treatment
The findings may shift the scientific perspective on long COVID’s biology and therapeutic strategies. Previous investigations have largely emphasized brain inflammation and immune dysregulation, whereas direct clinical trials targeting dopamine‑releasing neurons have been scarce.
Dr. Meyer adds, “These results suggest that long COVID is, at least partly, a disorder of the brain’s dopamine system. Consequently, repurposing drugs that enhance dopamine‑neuron function—such as dopamine precursors and metabolism inhibitors—may offer a promising therapeutic avenue.”
For individuals coping with long COVID, the discovery may also furnish a biological rationale for symptoms that are often hard to quantify externally.
“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.”
Clinical Trial Planned to Target Dopamine Function
Based on these insights, the investigators intend to launch a clinical trial within the next few months aimed at modulating dopamine function in patients with long COVID. The primary objective will be to assess whether altering dopamine activity can enhance memory, motivation, and reduce fatigue.
The trial will be carried out in partnership with the University Health Network (UHN), reflecting a collaborative effort to integrate mental and physical health care.
The research was supported by the Canadian Institutes of Health Research (CIHR).