Could low serotonin levels contribute to Long COVID?

Decreased levels of serotonin in the body may be a contributing factor in the development and persistence of so-called 'long COVID' symptoms, according to a new study.

Researchers suggest that, even after acute COVID symptoms subside, traces of the virus remain in the gastrointestinal tract, which is where the majority of circulating serotonin is produced, and where the virus reduces levels of the essential chemical. The low levels of serotonin might in turn lead to some of the more commonly reported long COVID symptoms, such as cognitive difficulties and memory problems, according to the study.

For the study, published Monday in the journal Cell, researchers at Penn Medicine conducted an analysis using questionnaire surveys and medical chart reviews of 1,540 patients hospitalized with long COVID.

Patients reported symptoms including fatigue, cognitive difficulties, headaches, anxiety, loss of endurance, problems with sleep, and memory loss – all typically associated with long COVID diagnosis.

The study also analyzed blood samples taken from 58 long COVID patients and compared them to samples taken from 30 people who were fully recovered from COVID, as well as to samples taken from 60 people in the midst of an active COVID infection.

"These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes," the authors wrote.

Researchers found that long COVID patients had different levels of chemicals in their body compared to those who had recovered, the most significant of which were levels of serotonin.

Serotonin is a neurotransmitter, sometimes referred to as the "feel good" chemical, that carries messages between nerve cells in the brain and throughout the body, helping to regulate mood. But serotonin also plays a significant role in digestion, sleep, bone health, wound healing, blood clotting and sexual desire, according to the Cleveland Clinic.

The researchers believe leftover bits of the virus in the gastrointestinal tract cause the body to produce proteins that lead to inflammation and an inability to absorb tryptophan, an amino acid that's essential for the production and maintenance of neurotransmitters, including serotonin. The resulting low levels of serotonin lead to memory problems and other cognitive issues.

Serotonin levels also were predictive of whether a patient in the study fully recovered or developed long-term complications after COVID infection. Serotonin levels remained reduced in severe cases of long COVID. Long COVID patients also had higher levels of enzymes in the body that can break down serotonin, which in turn may also reduce levels of the neurotransmitter.

Researchers say further studies are needed to confirm a causal link between low serotonin levels and long COVID, with further, multiple steps needed before the research can result in a treatment.

Long COVID is a condition that occurs when patients still exhibit symptoms at least four weeks after they have cleared the infection. In some cases, long COVID symptoms can be experienced for months or years.

Though symptoms often vary, they can include fatigue, difficulty breathing, headaches, brain fog, joint and muscle pain, and continued loss of taste and smell, according to the Centers for Disease Control and Prevention.

Despite the new findings about serotonin's possible role, it's unclear what causes people to develop long COVID, and research is ongoing.

Earlier this year, the Biden administration announced it was forming a new Office of Long COVID Research and Practice to study the condition and help those who have been diagnosed with it.

The office, which will be under the Department of Health and Human Services, "is charged with on-going coordination of the whole-of-government response to the longer-term effects of COVID-19," according to an HHS news release.