Study links Long COVID to fewer dopamine‑producing brain cells

People with Long COVID may have fewer brain cells that produce dopamine, a chemical that helps regulate movement, memory, motivation and mood, according to a new study. The findings provide new clues into why many people continue to experience symptoms such as fatigue, poor concentration, memory problems, lack of motivation and slowed movement long after recovering from the initial COVID-19 infection. Long COVID, also known as post-COVID-19 condition, is a condition in which symptoms persist or develop three months after a COVID-19 infection and cannot be explained by another illness. Common symptoms include fatigue, shortness of breath, "brain fog", memory problems, difficulty concentrating, headaches, muscle pain, sleep disturbances and loss of motivation, with symptoms that may last for months. These symptoms can affect multiple organs, but many patients report persistent neurological and psychiatric problems. Although previous research has suggested that inflammation in the brain may play a role, the exact biological mechanisms have remained poorly understood. The study, led by Jeffrey Meyer and published in eBioMedicine, examined whether Long COVID is associated with changes in the brain's dopamine system. Meyer and his team investigated whether damage to dopamine-producing nerve cells could explain some of these lingering symptoms. Dopamine is a neurotransmitter that plays a critical role in motivation, learning, memory, mood and the control of movement. The researchers noted that previous studies had identified inflammation in brain regions rich in dopamine-releasing nerve cells, raising the possibility that these neurons may be particularly vulnerable after COVID-19 infection. They conducted a case-control study involving 24 adults with Long COVID and 24 healthy adults of similar age, later expanding the healthy comparison group to 43 participants for additional analyses. “All participants with Long COVID had experienced mild to moderate COVID-19 during their initial infection but later developed persistent neuropsychiatric symptoms within three months that continued for at least another three months,” the research stated. To assess the health of dopamine-producing neurons, participants underwent positron emission tomography (PET) brain scans using a specialised tracer that measures a protein known as vesicular monoamine transporter 2 (VMAT2). This protein is found almost exclusively in dopamine-releasing nerve terminals, making it a reliable indicator of the integrity of these cells. Participants also completed a series of tests assessing memory, motivation, cognitive function and physical movement. Brain imaging revealed that participants with Long COVID had significantly lower levels of the dopamine transporter protein across three important regions of the brain compared with healthy participants. Overall, researchers estimated an average 18 per cent reduction in dopamine-releasing nerve terminals among people with Long COVID. The loss of dopamine activity closely matched the severity of participants' symptoms. Reduced dopamine levels in the ventral striatum, a brain region involved in motivation, were associated with greater apathy and more frequent cognitive difficulties. Lower dopamine activity in the dorsal putamen, which helps control movement, was linked to slower performance on finger-tapping tests that measure motor speed. Meanwhile, reduced dopamine function in the dorsal caudate, an area involved in learning and memory, was associated with poorer performance on memory tests. Researchers also analysed blood samples to determine whether routine blood markers could detect the same abnormalities seen on brain scans. However, they found no meaningful relationship between blood test results and the changes observed in dopamine-producing neurons. This suggests that conventional blood tests may not accurately reflect the neurological changes occurring in people with Long COVID. The researchers emphasised that the study does not prove that COVID-19 directly destroys dopamine-producing nerve cells. Because the research was observational and assessed participants at only one point in time, it can only demonstrate an association between reduced dopamine activity and Long COVID symptoms. They also noted that the brain scans measured dopamine transporter proteins rather than the neurons themselves, meaning the cells may still be present but functioning abnormally. The study also had several limitations. It included a relatively small number of participants, all of whom experienced prominent neurological and psychiatric symptoms. As a result, the findings may not apply to people whose Long COVID mainly affects the lungs, heart or other organs. Larger studies following patients over time will be needed to determine whether these dopamine-related changes are temporary, permanent or reversible. Despite these limitations, the findings point to a promising new direction for treatment. The researchers.