A groundbreaking brain imaging study led by researchers at the Centre for Addiction and Mental Health (CAMH) has uncovered what scientists are describing as the most compelling evidence to date that long COVID is fundamentally associated with physical damage to dopamine-releasing neurons in the brain. Published in the scientific journal eBioMedicine, these findings provide critical insights into the biological underpinnings of persistent, debilitating symptoms such as fatigue-related loss of motivation, motor slowing, and memory difficulties. Beyond illuminating the underlying pathology of the condition, the discovery opens vital new pathways toward targeted treatment strategies for millions of sufferers worldwide.
Long COVID remains a widespread and often misunderstood public health crisis, currently estimated to affect approximately five per cent of the global population. In Canada alone, the condition impacts roughly two million individuals. The illness is characterized by a diverse, unpredictable, and enduring broad range of symptoms that continue for at least three months following the initial acute phase of a SARS-CoV-2 infection. Among the most disruptive manifestations are neurological and cognitive symptoms, including profound fatigue, cognitive impairment commonly referred to as "brain fog," memory problems, and low mood. Despite how pervasive and life-altering long COVID can be for those who experience it, there are currently very few evidence-based treatments available. This therapeutic void exists largely because scientists and medical professionals have lacked a comprehensive understanding of the precise physiological disruptions occurring within the central nervous system.
Brain Scans Reveal Changes in the Dopamine System
To investigate the root causes of these persistent neurological symptoms, the research team utilized positron emission tomography (PET), an advanced imaging technique capable of measuring precise biological and chemical activity inside the living human brain. Using this technology, the investigators examined a well-established neurobiological marker directly associated with the health, density, and overall integrity of dopamine neurons in individuals suffering from long COVID. They then compared these diagnostic scans with results obtained from a control group of healthy participants.
The analysis yielded stark contrasts. The researchers discovered substantially lower levels of the dopamine neuron marker in individuals with long COVID across all major subregions of the striatum. The striatum is a complex and vital group of deep-brain structures that plays a fundamental role in regulating motivation, physical movement, and high-level cognitive thinking. These lower marker levels strongly indicate a reduced density of dopamine nerve terminals, pointing to actual cellular loss or injury within these critical pathways.
Furthermore, the study revealed distinct patterns of marker loss that closely corresponded with specific clinical symptoms experienced by the patients. Lower marker levels located specifically within the ventral striatum were directly linked to a greater loss of motivation and drive. Meanwhile, reductions observed in the dorsal putamen were strongly associated with slower physical movement and motor delays. Additionally, lower levels detected in the caudate putamen were reliably connected to persistent 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."
Earlier Research Pointed to Brain Inflammation
These new discoveries do not exist in a vacuum; rather, they build directly upon previous pioneering work conducted by the exact same research team. Earlier studies demonstrated that individuals suffering from long COVID exhibit unusually high levels of neuroinflammation—or inflammation within the brain. Crucially, that inflammation appeared to be especially pronounced and concentrated in neurological regions containing large numbers of 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.
When viewed together, these two successive studies construct a compelling narrative, suggesting a direct biological connection between persistent, chronic brain inflammation and the subsequent physical damage involving the brain’s dopamine system. This mechanistic link helps bridge the gap between immune system response and long-term neurological decline.
A New Direction for Long COVID Treatment
The implications of these results are profound and have the potential to fundamentally alter how researchers, pharmacologists, and clinicians approach the biology and treatment of long COVID. Historically, a significant majority of previous research efforts have centered almost exclusively on generalized inflammation in the brain and systemic changes in immune activity. By comparison, very few clinical trials or therapeutic interventions have focused directly on protecting or restoring 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 the millions of people living with long COVID, these findings offer something long denied to them by the medical establishment: a concrete, biological explanation for severe, debilitating symptoms that can frequently be difficult to observe, quantify, or measure from the outside.
"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
Capitalizing on the momentum of these recent results, the research team is wasting little time in translating laboratory discoveries into practical clinical applications. Plans are currently underway to initiate a comprehensive clinical trial within the upcoming couple of months. This upcoming study will directly target dopamine function in human participants suffering from long COVID.
The primary objective of the clinical trial will be to determine whether medically modifying and supporting dopamine activity can successfully alleviate symptoms, improving memory retention, restoring motivation, and mitigating chronic fatigue.
The upcoming trial will be conducted in close collaboration with the University Health Network (UHN), operating as part of a strategic partnership between the participating hospitals designed specifically to bridge the longstanding gap between mental and physical health care. The underlying research study itself received financial support and backing from the Canadian Institutes of Health Research (CIHR).