Brain scans link long COVID fatigue and fog to lost dopamine neurons

Researchers at Toronto’s Centre for Addiction and Mental Health have found the first direct brain evidence for a cause of the exhaustion and mental fog that trail long COVID: a measurable loss of dopamine-releasing neurons deep in the brain. Using positron emission tomography, the team scanned people with long COVID and compared them to healthy volunteers, tracking a marker that reflects how many dopamine neurons are intact. Patients showed substantially lower levels of that marker across every major region of the striatum, the brain structure that governs motivation, movement and memory. The finding gives a biological name to symptoms doctors have struggled to explain for years.

Mapping dopamine loss across the striatum

The study, published in the journal eBioMedicine, was led by Jeffrey Meyer, a senior scientist at CAMH’s Brain Health Imaging Centre and a Canada Research Chair, with graduate student Yuhan Liu as first author. Rather than scanning the whole brain as a single unit, the team mapped the marker separately across the striatum’s subregions and matched each region’s dopamine loss to the specific symptoms patients reported. Loss in the ventral striatum tracked with reduced motivation. Loss in the dorsal putamen lined up with slowed movement. Loss in the caudate putamen was tied to memory difficulties, giving researchers a region-by-region explanation rather than a single vague marker of “brain fog.”

“[The] findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons,” Meyer said. “This kind of injury is well known to produce symptoms like lack of motivation and motor slowing.” He added that the pattern points to something more specific than generalized inflammation or fatigue: “These results indicate that long COVID is, at least in part, a disorder of the brain’s dopamine system.”

A biological target for a condition without one

Long COVID is estimated to affect about 5% of the global population, including roughly two million people in Canada, and much of that burden has gone untreated because doctors had no agreed biological mechanism to target. Fatigue, cognitive fog and low motivation are common across many conditions, which has made it difficult for clinicians to distinguish long COVID from depression, chronic fatigue syndrome or simple deconditioning. A dopamine-specific finding narrows that ambiguity considerably, because dopamine pathways already have decades of drug development behind them from Parkinson’s disease and other movement disorders.

CAMH plans to test that existing pharmacology directly. Meyer’s team, working with University Health Network, intends to launch a clinical trial within the next couple of months that targets dopamine function directly in people with long COVID, aiming to improve memory, motivation and fatigue rather than treating symptoms individually. It would be among the first trials to use a brain-imaging finding in long COVID to select a specific drug mechanism rather than repurpose a general antiviral or anti-inflammatory approach.

Open questions the PET scans leave behind

The imaging does not establish why the virus, or the body’s response to it, would damage dopamine neurons specifically. Meyer’s group has previously linked long COVID to broader neuroinflammation, and the current findings sit alongside that work rather than replacing it; the dopamine loss could be a downstream effect of inflammation rather than a separate, direct injury. A summary of the findings distributed to the scientific press noted that the imaging technique used, which measures a transporter protein tied to dopamine storage, cannot by itself distinguish whether neurons have died outright or are simply functioning at reduced capacity.

Independent coverage of the peer-reviewed paper has emphasized that the affected patients were drawn from people with persistent, often severe symptoms rather than a random sample of everyone who has had COVID-19, meaning the scale of dopamine loss described may not apply to milder or shorter cases of the condition. Meyer’s team has not yet published data on whether the deficit changes over time, on its own or with treatment, and the current paper describes a single scan per participant rather than repeated imaging that could show whether the neurons keep declining.

That gap matters because long COVID itself is not a single, fixed condition. Some patients recover within months; others report symptoms lasting years, and it is not yet known whether those different trajectories map onto different degrees of dopamine loss. Meyer’s group has said future work will need larger patient groups, drawn from both recent and long-standing cases, before doctors can use a dopamine scan to predict how a given patient’s illness will unfold.

Still, for patients who have spent years being told their exhaustion and forgetfulness were psychological rather than physical, a scan that shows a specific brain system underperforming is a different kind of answer. Researchers elsewhere have already begun citing the CAMH data in broader discussions of long COVID’s biological toll on the brain, treating it as evidence that the condition’s cognitive symptoms have a physical substrate that imaging can now actually see.

Whether restoring dopamine function reverses the symptoms, or only slows their progression, is the question Meyer’s upcoming trial is designed to answer.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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