Long COVID tied to dopamine deficits in brain imaging study

Clinical takeaway: Long COVID's brain symptoms may reflect a measurable dopamine deficit rather than a purely functional or psychological problem, which could reshape how clinicians frame these complaints with patients.

Fatigue, low motivation, slowed movement, and memory trouble are among long COVID's most disabling symptoms, and among the least understood. With no measurable brain finding to anchor them, these complaints have often been treated as functional or psychological. A new PET study offers a physical correlate: people with long COVID showed reduced dopamine-neuron markers in a brain region central to motivation, movement, and thinking.

The study builds on the team's earlier finding that people with long COVID have elevated inflammation in the same dopamine-rich brain regions. Inflammation is known to injure dopamine neurons, so the group examined whether the neurons themselves showed damage. This scan measured that directly.

People with long COVID had lower dopamine-neuron markers than healthy controls across all major parts of the striatum, the brain's hub for motivation, movement, and thinking, with reductions of about 16% to 20% by region. The regional pattern tracked with symptoms: lower markers in the ventral striatum went with greater loss of motivation, reductions in the dorsal putamen with slower movement, and losses in the caudate with memory trouble.

People who had recovered well from COVID showed no such deficit and looked no different from those never infected, which points to the finding tracking with the long COVID syndrome itself rather than with prior infection. The PET tracer measures dopamine-terminal density, so a lower signal points to fewer or less active dopamine terminals rather than proving neurons have died.

The case-control study used PET imaging to compare striatal dopamine-terminal markers in 24 adults with long COVID against age-matched healthy controls, with long COVID defined as symptoms persisting at least three months after infection. The sample was young, unmedicated, and non-smoking, which sharpens the dopamine signal but limits how far the numbers extend to the older, medicated patients seen in practice.

The authors frame the results as a case for testing dopamine-increasing drugs in long COVID, and say a trial is planned using agents such as levodopa and rasagiline. None has been tested for this use yet.

"Our findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons. 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," said Jeffrey Meyer, MD, PhD, senior scientist at the Brain Health Imaging Centre at CAMH and senior author of the study.

Source: Liu Y, et al. (2026 Jul 10) eBioMedicine. Loss of vesicular monoamine transporter 2 in striatum of long COVID and relationship to neuropsychiatric symptoms