Does Dopamine Loss Trigger Brain Symptoms in Long COVID?

Long COVID, a post-viral syndrome that affects up to 5% of the world’s population, is often characterized by symptoms such as brain fog, apathy, and slow motor movements. Evidence-based treatments have been lacking because the underpinnings of these brain symptoms are poorly understood. Now, a new study provides evidence of injury to dopaminergic neurons in the brain, suggesting a potential new therapeutic avenue for long COVID.1. Why Dopamine?Dopamine terminals in the brain striatum are vulnerable to viral-induced inflammation, as well as direct infection of dopamine-releasing neurons. A loss of dopaminergic neurons, a feature of other neurological conditions, is associated with some of the same brain symptoms seen in long COVID. 2. A Case-Control StudyResearchers measured vesicular monoamine transporter 2 (VMAT2) levels, a marker of dopaminergic nerve terminal integrity, to see whether it was reduced in the striatum and whether lower dopamine nerve terminal density correlates with patient symptoms and findings of neuropsychiatric and other tests of movement, motivation, and cognition. Between 2022 and 2025, researchers used PET imaging to scan adults with long COVID.3. Key FindingCompared with healthy age-matched controls, participants with long COVID had lower VMAT2, potentially representing a loss of dopamine-releasing neurons.4. Matching Scans and SymptomsThe pattern of lower VMAT2 mapped onto patient symptoms by brain region: lower ventral striatum binding correlated with reduced motivation, lower dorsal putamen binding with slowed movements, and lower caudate changes correlated with memory problems, including an unhypothesized but notably strong link to delayed verbal memory.5. A New Direction for Long COVID TreatmentAn independent commenter emphasized that identifying the mechanism underlying a patient’s symptoms allows clinicians to match the patient to effective treatment. Several existing drug classes — dopamine precursors and inhibitors of dopamine metabolism — could plausibly be repurposed for the management of long COVID. Next, the research team plans to launch a trial targeting both the inflammatory changes seen in long COVID and the dopamine terminal loss identified in the current study.Bottom LineThis study suggests moving beyond brain inflammation as the sole cause of the persistent neuropsychiatric symptoms of long COVID. Dopaminergic injury is a biologically plausible contributor to the cognitive issues reported by patients, thus interventions targeting the dopamine system might have therapeutic benefit. The evidence is early, from a single small case-control study, and doesn't yet support prescribing of drugs that enhance dopamine availability or function.This article is based on a recent Medscape News Canada article titled "Long COVID Associated With Injury to Dopamine System", and was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.