A new study published in the journal Cell reveals that COVID long-haulers struggling with symptoms such as brain fog, fatigue, and memory loss show lower levels of serotonin, a neurotransmitter that fills many important roles in the body, including cognition, mood regulation, learning, and memory. It’s also involved in physiological functions such as blood vessel constriction, digestion, wound healing, and sleep. Learn what the study findings on low serotonin could mean for Long COVID treatment.*

What the researchers did

The research team, from the Perelman School of Medicine at the University of Pennsylvania, evaluated the effects of Long COVID in blood and stool samples from various clinical and preclinical studies.

From the samples, they established that a group of patients still had traces of the SARS-CoV-2 virus in their stool months after their infection, meaning that some part of the virus remained in their gut. Pockets of virus that hide in the body are called ‘viral reservoirs.’

What they found

These lingering viral pockets, the researchers said, signal the immune system to generate and release proteins to fight off the virus cells. The proteins, called interferons, lead to inflammation, and the inflammation lowers the absorption rate of tryptophan in the gut. 

Tryptophan is an amino acid, and is necessary for the production of serotonin, a neurotransmitter that is mostly generated in the gastrointestinal tract to transport chemical messages throughout the brain and body. It also helps regulate the vagus nerve, which is the main highway of communication between the gut and the brain.

The research team discovered that:

• Persistent viral inflammation reduces tryptophan absorption
• Reduced tryptophan absorption depletes circulating serotonin levels
• Depleted serotonin levels disrupts vagus nerve signaling
• Disrupted vagus nerve signaling can cause various symptoms, such as memory loss, associated with Long COVID. 

Based on these results, the study authors did a test using small mammals to see if reversing tryptophan or serotonin deficiencies could treat and reverse the related Long COVID symptoms. 

They found that serotonin levels could be restored, and memory impairment reversed, with the use of serotonin precursors or selective serotonin reuptake inhibitors (SSRIs).

What it means

The results of both studies are significant, and encouraging, the authors wrote, recommending additional studies to confirm serotonin as a viable treatment target, and SSRIs as safe and effective therapies for several Long COVID symptoms. This could address not only neurological symptoms, but also excessive blood clots and autonomic isses involving heart rate and blood pressure. 

 “These effects can explain a wide spectrum of symptoms that our patients with Long COVID have,” said Benjamin Abramoff, study co-author and director of Penn Medicine’s Post-COVID Assessment and Recovery Clinic. 

“We found that it’s really across the board that these decreases of serotonin are noted, so it’s not only in those with neurocognitive effects, but also with pulmonary effects and cardiovascular dysfunction.”

According to Maayan Levy, Ph.D., senior author and an assistant professor of microbiology at Penn Medicine, the team’s findings can “help to untangle some of the mechanisms that contribute to Long COVID” as well as aid doctors in diagnosing, prescribing appropriate treatments, and measuring patients’ responses to individual therapies.

“Our study,” added co-author Christoph Thaiss, Ph.D.,“provides a unique opportunity for further research to determine how many individuals with Long COVID are affected by the pathway linking viral persistence, serotonin deficiency, and dysfunction of the vagus nerve, and to uncover additional targets for treatments across the different symptoms patients experience.”

*Penn Medicine News. (2023, October 16). Viral Persistence and Serotonin Reduction Can Cause Long COVID Symptoms, Penn Medicine Research Finds. https://www.pennmedicine.org/news/news-releases/2023/october/penn-study-finds-serotonin-reduction-causes-long-covid-symptoms