'Long COVID Associated With Injury to Dopamine System'

 Long COVID may be associated with injury to the dopamine system, according to a new Canadian study.

The findings of this case-control study may explain symptoms such as lack of motivation due to fatigue, slowed movement, and memory difficulties. They also could open the door to new treatment strategies.

The current research was prompted by earlier findings showing an association between inflammation in the brain and long COVID. “We’ve done previous work looking at markers of gliosis and inflammation in long COVID and found that the striatum had prominent alterations with COVID,” senior author Jeffrey Meyer, MD, senior scientist and Canada Research Chair in the Neurochemistry of Major Depression at the Centre for Addiction and Mental Health in Toronto, told Medscape News Canada.

“We’d also found that dopamine-releasing neurons have a high concentration of ACE2 binding sites, so this could potentially be a way that the virus could affect dopamine-releasing neurons,” said Meyer.

The data were published on July 10 in eBioMedicine.

Lower Dopamine Nerve Terminal Density

Long COVID is estimated to affect 5% of the world population, including two million Canadians. It’s characterized by a wide range of persistent and sometimes debilitating symptoms that continue for at least three months following the initial COVID infection. Brain-related symptoms include fatigue, brain fog, memory problems, or low mood.

While dopaminergic neurons are vulnerable to injury from gliosis and have a high density of ACE2 receptors, this was the first study to investigate the integrity of dopaminergic neurons in long COVID. The researchers examined whether vesicular monoamine transporter 2 (VMAT2) binding, an index of dopamine-releasing neuron density, is reduced in the striatum in long COVID and associated with neuropsychiatric symptoms. The striatum plays a central role in motivation, movement, and thinking.

The study took place from 2022 to 2025 in Toronto and included 24 adults with long COVID and 24 age-matched healthy control individuals. The control sample was extended to 43 participants for exploratory analyses.

Researchers used PET brain imaging to measure VMAT2 binding in patients with long COVID and control individuals.

The researchers found significantly lower levels of the imaging marker, indicating reduced dopamine nerve terminal density across all major regions of the striatum, in patients with long COVID, compared with control individuals. Lower levels in the ventral striatum were associated with greater loss of motivation, lower levels in the dorsal putamen were associated with slowed movement speed, and lower levels in the caudate were linked to memory difficulties.

“We also found a relationship between loss of dopamine nerve terminals in the caudate with problems of delayed verbal memory,” said Meyer. “Even though it wasn’t hypothesized a priori, it’s a strong association.”

New Applications for Current Meds

Commenting on the study for Medscape News Canada, Christine DeLorenzo, PhD, professor of psychiatry and biomedical engineering and director of the Center for Understanding Biology using Imaging Technology at Stony Brook University in Stony Brook, New York, said that the results matter because it’s important to understand the mechanism of any disorder or set of symptoms to treat the patient.

“If you have a patient with long COVID, how are you going to intervene to help that patient? You don’t know what your options are and what you can do unless you know what the problem is,” she said. Studies using PET imaging point clinicians to specific sets of treatment, she added. “This is critically important in all of psychiatry because we struggle to pinpoint the exact biology and pair the treatment to the individual.”

Medications that augment the function of dopamine-releasing neurons, including dopamine precursors and inhibitors of dopamine metabolism, could be used to treat long COVID, said Meyer. “Because there are a lot of medications already available to influence dopamine-releasing neurons, we have quite a range of potential clinical trials ahead to look at what might be helpful in the area of manipulating these neurons to help people recover. This is a research field that remains untapped in clinical trials today,” he said.

“We anticipate starting a clinical trial targeting dopamine function to help with memory, motivation, and fatigue in patients with long COVID in collaboration with University Health Network in the next 2 months. That trial will address the inflammatory changes we’ve found in our previous work, as well as the problem of lack of dopamine-releasing nerve terminals,” Meyer concluded.

The study was supported by the Canadian Institutes of Health Research. Meyer has patents for a dietary supplement to prevent postpartum blues and postpartum depression and has received funding from CAMH and Exeltis for that research. He also owns stock in Moderna and has applied for patenting for rasagiline and a dopamine precursor approach of tyramine use for an indication of long COVID. DeLorenzo reported having no relevant financial relationships. 

https://www.medscape.com/viewarticle/long-covid-associated-injury-dopamine-system-2026a1000o0u