For years, patients with long COVID have described neurologic symptoms like brain fog, memory problems, difficulty concentrating, and lack of motivation, but scientists have struggled to identify the biology behind these symptoms. Now, a new study suggests they may be tied to measurable changes in the brain’s dopamine system.

For the study, published in eBioMedicine, researchers led by a team from the Brain Health Imaging Centre in Toronto and the University of Toronto used positron emission tomography (PET) brain imaging to measure vesicular monoamine transporter 2 (VMAT2), a marker of dopamine neuron integrity, in 24 adults with long COVID and persistent neuropsychiatric symptoms and in 24 healthy controls. 

The team found lower levels of VMAT2, which indicates reduced dopamine nerve terminal density, in the brains of people with long COVID and neuropsychiatric symptoms compared with the control group. The lower levels of VMAT2 were identified in a region of the brain called the striatum, which plays key roles in reward and motivation, movement and motor control, and cognition—the brain’s ability to think and process information. 

“This kind of injury [loss of dopamine-releasing neurons in the brain] is well known to produce symptoms like lack of motivation and motor slowing.”

“Our findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons,” senior scientist at the Brain Health Imaging Centre and senior study author, Jeffrey Meyer, MD, PhD, said in a news release from the Centre for Addiction and Mental Health, which houses the Brain Health Imaging Centre. 

“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.”

Possibilities for new long-COVID therapies

Compared with healthy controls, participants with long COVID had 16% to 20% lower VMAT2 across three regions in the striatum. The largest differences were observed in the dorsal putamen, which is involved in movement, and the dorsal caudate, which is associated with memory. The smallest difference was observed in the ventral striatum, which is involved with motivation and reward. 

The findings help shine a light on some of the biological processes that may be involved in long COVID, note Eric Guedj, MD, PhD, of Aix Marseille University in France, and Danielle Beckman, PhD, PharmD, of Helmholtz Munich, in an accompanying commentary.  “This work shifts the discussion from symptom description to mechanistic stratification,” they write. “By linking neuropsychiatric symptoms to a presynaptic dopaminergic marker, it reframes part of the long COVID spectrum as a measurable brain-network phenotype.”

Guedj and Beckman also note that these changes are not necessarily permanent, and more longitudinal studies are needed to determine their clinical significance. 

These results indicate that long COVID is, at least in part, a disorder of the brain’s dopamine system.

The study has several limitations, including a small sample size and a focus on long-COVID patients with significant neuropsychiatric symptoms. The findings also show only an association; they cannot prove causation. 

Still, the findings may offer hope to those with long-COVID-related neuropsychiatric symptoms. “These results indicate that long COVID is, at least in part, a disorder of the brain’s dopamine system,” says Meyer in the release. “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 ap