Long COVID May Damage Dopamine Neurons in the Brain

Scientists have identified a distinctive alteration in the brains of people with long COVID that could account for some of the condition's most disabling symptoms.

In some patients, dopamine neurons may have been harmed or become exhausted.

Long COVID and dopamine neurons

This remains an initial hypothesis. However, a preliminary Canadian study involving 24 people with long COVID detected clear differences in certain brain areas when compared with healthy people of the same age.

The more severe participants' memory deterioration, slowed physical movement and lack of motivation were, the larger the measured differences in their dopamine nerve endings.

"Our findings provide compelling evidence that long COVID involves the loss of dopamine-releasing neurons," says psychiatrist Jeffrey Meyer from the Brain Health Imaging Center in Canada.

"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."

Earlier research in people with long COVID has largely examined inflammation in the brain and changes to the immune system. Yet no previous study had directly assessed whether dopamine-producing neurons in the brain were affected.

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

Dopamine is widely recognised as the 'feel-good' hormone. It is an essential chemical messenger in the brain and is strongly connected with its reward system.

There are, however, grounds to think dopamine circuits could be susceptible to damage during long COVID.

People with long COVID have raised markers for certain brain cells that trim synapses. This process could harm dopamine-releasing neurons.

It is also possible that SARS-CoV-2 directly infects dopamine-releasing neurons, causing damage from inside the cells.

These brain cells generally contain a high concentration of receptors to which SARS-CoV-2 could, in theory, attach.

PET scans reveal changes in the striatum

Using positron emission tomography (PET) scans and a radioactive tracer, the Canadian researchers measured a marker associated with dopamine nerve endings in 24 participants with long COVID.

None of the participants had an active infection. All had, however, experienced persistent and debilitating symptoms since first becoming ill with COVID. Each reported some degree of reduced motivation, while the group performed more poorly in tests of memory and movement speed.

Against healthy controls, their brain scans showed a lower density of dopamine nerve endings across several regions of the striatum.

This area of the brain plays a role in motivation, movement speed and memory.

The intensity of certain long COVID symptoms in patients correlated with the density of their dopamine neurons.

This points to a relationship between the two.

Approximately 25 percent of the variation in these symptoms among people with long COVID was linked to a loss of dopaminergic neurons.

"The present study makes a case for a hypothesis that interventions targeting dopamine-releasing neurons in long COVID would have therapeutic impact," the authors conclude.

"This is a notable shift from present therapeutic development, given that no current trials focus on augmenting functions of dopamine-releasing neurons."

These brain scans detect a protein present on dopamine nerve endings, rather than directly measuring neuron density.

Even so, they are highly useful for examining brain changes in living patients.

Dopamine-releasing neurons can only be studied directly by examining brain tissue after death.

A small autopsy study reported fewer dopamine neurons in people who died with severe COVID-19. Most participants in that study were older, though, and some showed evidence of early dementia, including one individual with Parkinson's, which complicates the findings.

Potential Parkinson's treatments for long COVID

The new research is preliminary only, but it raises the possibility that long COVID affects dopamine-releasing neurons in ways that are broadly comparable with Parkinson's.

Should this be confirmed, medicines such as L-dopa, used to treat Parkinson's, might theoretically be repurposed for people with long COVID.

"These interventions would enhance tonic dopamine release broadly, and phasic release in intact synapses, thereby reducing impact of lost synapses," the study authors theorize.

Nonetheless, these medicines should not be used casually because they can cause substantial side effects.

They might also be effective only for patients with a particular form of long COVID. Symptoms of this post-viral condition vary greatly, and not every patient experiences slower physical movements, low motivation or worsening memory.

Other forms of long COVID may not affect dopamine neurons in the same manner.

The researchers call for future work in larger, equally well-controlled cohorts to establish whether the findings are robust and generalisable. It is also worth noting that Meyer has a pending patent application for a dopamine-based long COVID treatment.

Susan Deuville, who has long COVID, serves as a lived-experience research adviser to Meyer.

"For five years I have been seeking answers on what happened to me after I contracted COVID in 2021," says Deuville.

"It was a crushing loss of the life I had and the person I was before. The research of Dr Meyer brings hope. It also validates what long COVID sufferers have always known – long COVID is real, and the effects are devastating."

The research was published in eBioMedicine.

This article was fact-checked and edited by Rebecca Dyer. Although we take pride in our process, we are only human. If you notice an error, please tell us.