Science1 publisher2 min readPublished
Scans of 24 long COVID patients tie slowed movement and low motivation to depleted dopamine nerve endings
Canadian researchers scanning 24 people with long COVID found fewer dopamine nerve endings in the striatum, a shortfall tied to a quarter of symptom variance. The result gives drug trials a dopamine hypothesis to test, though the scan reads a protein marker that stands in for the neurons themselves.
The Scientist · Science desk
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What happened
- None of the 24 patients had an active infection, yet all had persistent symptoms, and as a group they scored worse on tests of memory and movement speed.
- Patients with worse memory decline, slower movement and less motivation showed larger differences in dopamine nerve endings than patients with milder symptoms.
- Earlier long COVID brain studies focused mainly on inflammation and immune changes, and none had directly examined dopamine-producing neurons.
- In a small autopsy study, people who died with severe COVID-19 had fewer dopamine neurons. That result is confounded, because most of them were elderly and one had Parkinson's.
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Why it matters
- decision Trial sponsors now have a concrete option to weigh: testing dopamine-boosting drugs in long COVID patients chosen for low striatal PET signal.
- constraint About three-quarters of symptom variation lies outside the dopamine measure, and not every patient reports slowed movement, so a dopamine drug would at best help a subset.
- exposure Patients who try Parkinson's drugs such as L-dopa ahead of trials take on significant side effects for a benefit shown so far only as a correlation in 24 people.
The quarter of symptom variance linked to the dopamine measure [5] works out to a correlation coefficient of roughly 0.5 [2]. For a first look at 24 people [1], a correlation that size deserves attention.
Jeffrey Meyer, a psychiatrist at the Brain Health Imaging Center in Canada, put the finding strongly. "Our findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons," he said [6]. He also gave a narrower version: "These results indicate that long COVID is, at least in part, a disorder of the brain's dopamine system" [7]. I think a quarter of the variance supports the second sentence better than the first [5].
Loss is a strong word for what the scanner sees. Compared with healthy people of the same age, the patients showed reduced density of dopamine nerve endings in several regions of the striatum, a structure involved in motivation, movement speed and memory [3]. The PET scans used a radioactive tracer to measure a protein found on those nerve endings, so the reading tracks neuron density one step removed [2][8]. Counting the neurons themselves requires postmortem tissue [8].
The inflammation work and the dopamine finding need not compete. One proposed route to dopamine injury runs through brain cells that prune synapses, whose markers are elevated in people with long COVID [11]. If that route holds, inflammation and dopamine loss would be steps in one chain. The other candidate is direct infection, since dopamine-releasing neurons carry a high density of receptors that SARS-CoV-2 could in theory bind [16].
According to ScienceAlert, the study hints that long COVID may affect these neurons in broadly similar ways to Parkinson's [19]. If that is verified, Parkinson's drugs such as L-dopa could in theory be repurposed [13]. The authors spell out how such drugs would help: "These interventions would enhance tonic dopamine release broadly, and phasic release in intact synapses, thereby reducing impact of lost synapses," they wrote [20]. They call the idea "a notable shift from present therapeutic development, given that no current trials focus on augmenting functions of dopamine-releasing neurons" [12].
The thing this study doesn't tell you is direction. A correlation across 24 patients [1][4] cannot show whether the lower dopamine signal came before the symptoms, after them, or alongside them from a shared cause. ScienceAlert's account also does not say how many healthy controls were scanned.
What to watch
- A larger replication with repeated scans over time, which would show whether the dopamine signal falls before or after symptoms appear.
- A controlled trial of a dopamine-augmenting drug such as L-dopa in long COVID patients selected by low striatal PET signal.
- Postmortem studies of younger long COVID patients without dementia or Parkinson's, which would test the neuron-loss reading directly.