Long COVID study links cognitive symptoms to dopamine system damage

A novel study has revealed that long COVID may involve injury to the brain’s dopamine system, offering a critical biological explanation for persistent neurological symptoms such as fatigue, cognitive impairment, and motor dysfunction. The research, led by scientists at Canada’s Centre for Addiction and Mental Health (CAMH), utilized positron emission tomography (PET) imaging to demonstrate reduced dopamine nerve terminal density in key brain regions of long COVID patients, marking the first direct evidence of such damage. The findings, published in *eBioMedicine*, suggest that dopamine dysfunction could underpin many of the condition’s hallmark symptoms and open new pathways for treatment.

The study compared dopamine-related markers in individuals with long COVID to those of healthy controls, finding significantly lower levels of a well-established PET imaging marker across the striatum — a brain region central to motivation, movement, and cognition. Specific patterns of dopamine loss correlated with distinct symptoms: reduced markers in the ventral striatum were linked to diminished motivation, while lower levels in the dorsal putamen associated with slower movement, and decreased activity in the caudate putamen correlated with memory difficulties. These results align with clinical observations of long COVID patients, who often report fatigue, brain fog, and impaired concentration.

Researchers at CAMH, including senior scientist Dr. Jeffrey Meyer, emphasized that the findings challenge previous assumptions about long COVID’s mechanisms. “This kind of injury is well known to produce symptoms like lack of motivation and motor slowing,” Meyer said, noting that similar processes occur in other neurological conditions. The study builds on earlier work by the team showing elevated brain inflammation in long COVID patients, particularly in dopamine-rich regions. “Inflammation can injure dopamine neurons,” Meyer explained, adding that the new evidence directly ties this inflammatory process to measurable dopamine system damage.

The implications for treatment are significant. The research suggests that repurposing medications targeting dopamine function — such as precursors or metabolism inhibitors, could alleviate persistent symptoms. CAMH plans to launch a clinical trial within months, in collaboration with University Health Network, to test these approaches. “This indicates that long COVID is, at least in part, a disorder of the brain’s dopamine system,” Meyer said, highlighting the potential for mechanism-based therapies. For patients like Susan Deuville, a lived-experience research adviser, the study provides validation. “The research of Dr. Meyer brings hope. It also validates what long COVID sufferers have always known, long COVID is real,” she said.

While the dopamine-focused study dominates the narrative, other research underscores the complexity of long COVID. A separate Yale-led investigation, published in *CELL*, identified autoimmune responses in some patients, where the immune system mistakenly attacks brain and nervous system tissues. This study found autoantibodies targeting regions involved in pain, memory, and autonomic function, leading to symptoms like fatigue and cognitive fog in mice. “This is one possible cause of long COVID, but it will likely have other trigger causes as well,” said co-senior author Akiko Iwasaki. The findings suggest that long COVID may overlap with autoimmune disorders, though no single mechanism explains all cases.

Meanwhile, a study in *Alzheimer’s & Dementia* linked long COVID to brain changes resembling early neurodegenerative patterns, such as enlarged choroid plexus and reduced cerebral blood flow. These alterations were associated with cognitive decline and sleep disturbances, raising questions about long-term dementia risk. However, researchers cautioned that the study’s small sample size and age disparities limited its conclusions, calling for larger trials to confirm the connection.

Despite these varied angles, the dopamine study represents a pivotal step in understanding long COVID’s biological underpinnings. With an estimated 5% of the global population affected, including 2 million Canadians, the condition remains a critical public health challenge. The CAMH team’s work not only provides a tangible link between brain changes and symptoms but also points toward therapies that could transform care. As one patient put it, “The research of Dr. Meyer brings hope” for millions grappling with the lingering effects of the pandemic.