Long COVID’s brain fog finally has a biological explanation: Dopamine loss

After years of long COVID being defined predominantly by patients' reported symptoms such as fatigue, brain fog, and memory loss, a new study from researchers at the Centre for Addiction and Mental Health and the University of Toronto may finally provide a biological explanation. Led by Jeffrey Meyer, a psychiatry professor at the University of Toronto, the study utilized PET imaging to measure the protein VMAT2, which is found on the nerve terminals that release dopamine, in both long COVID patients and healthy individuals who experienced only mild or moderate initial infections.

The findings revealed that patients with long COVID had significantly lower levels of VMAT2 across several brain regions responsible for motivation, movement, and memory. The reduction varied from 16% in the region associated with planning to 20% in the region most closely linked to motivation and apathy. This connection between lower dopamine levels and specific symptoms strengthens the link between the condition and these reported experiences.

The study builds upon a 2023 research from Meyer's team, which found elevated inflammation in the same brain regions. While inflammatory cells can damage dopamine-releasing nerves or cause nerve damage that leads to inflammation, this study uniquely demonstrates the correlation between the observed dopamine loss and specific symptoms.

For instance, damage in the ventral striatum region linked to apathy correlated with memory issues, while damage in the dorsal putamen region tied to planning aligned with slower movement. This breakthrough offers a clear biological marker for long COVID, overcoming the previous lack of objective evidence to support the diagnosis.

By pinpointing the specific loss of dopamine nerve terminals, researchers are now better positioned to conduct targeted studies and potentially develop new treatments. While the extent to which dopamine loss is reversible remains unclear, some patients may recover as damaged nerve terminals regenerate or form new connections, particularly through exercise or activities that engage the affected brain regions.

Conversely, ongoing inflammation may impede this recovery process, necessitating targeted treatments rather than simply waiting for improvement. Meyer's team is currently preparing a clinical trial to repurpose an existing dopamine-related medication that has already shown promising results in some patients. However, securing funding for this trial has been challenging, with the proposal narrowly missed two funding rounds in a row.

Ultimately, the good news is that while some individuals may recover through effort and adaptation, others may require medical intervention to achieve a full cure.