Link Found Between Persistent COVID-19 Symptoms and Serotonin Levels

Investigators at the Perelman School of Medicine at the University of Pennsylvania have identified a correlation between reduced serotonin levels and the prolonged symptoms experienced by long COVID patients, which persist after initial recovery from a COVID-19 infection.

The remnants of the SARS-CoV-2 virus persisting in some individuals’ gastrointestinal tracts appear to cause ongoing inflammation, abnormalities in the function of the vagus nerve, and a range of neurological issues.

Those who suffer from long COVID—enduring conditions such as cognitive difficulties, fatigue, and memory deficits that persist for months or even years after a COVID-19 illness—often show a decrease in the neurotransmitter serotonin in their systems. This was highlighted in a study published on October 16 in the journal Cell, conducted by a team from the Perelman School of Medicine at the University of Pennsylvania. The study offers insights into how continuous inflammation from a SARS-CoV-2 infection can lead to lasting neurological issues.

The CDC notes that around 20% of American adults who have been infected with COVID-19 end up with long COVID symptoms. These symptoms commonly include cognitive disruption, challenges with focusing, memory issues, widespread exhaustion, and headaches. The processes behind long COVID are not well understood, and universally effective treatment options to alleviate these long-lasting symptoms are yet to be established.

Insights from Research into the Biology of Long COVID

“The fundamental biology behind long COVID is still largely a mystery, which has hindered the development of precise diagnostic and therapeutic tools,” commented Maayan Levy, PhD, an assistant professor of Microbiology at Penn Medicine and the study’s senior author. “Our discovery could pave the way for not only understanding the disease better but also for biomarkers that can aid in diagnosing patients and evaluating the effectiveness of specific treatments.”

Tracing the Continuum from Acute COVID-19 to Long COVID

A collaborative study involving the Microbiology, Pathology and Laboratory Medicine departments and the Post COVID Assessment and Recovery Clinic’s Physical Medicine and Rehabilitation at Penn, assessed the impacts of long COVID using blood and fecal samples from various clinical studies and rodent models.

The findings indicate that certain long COVID patients retain traces of the SARS-CoV-2 virus in their fecal matter long after the initial viral infection. This suggests that viral remnants can linger in the gut. These remnants activate the immune system to produce interferons to combat the virus, leading to inflammation that hinders the absorption of tryptophan in the gastrointestinal tract.

Tryptophan is essential for creating several neurotransmitters, including serotonin, which is largely synthesized in the GI tract. Serotonin is involved in the brain’s nerve signaling and regulates many bodily functions, such as memory, sleep, digestion, wound healing, and overall body homeostasis. It also plays a critical role in the operation of the vagus nerve, which connects the body to the brain.

When inflammation from the virus impedes tryptophan absorption, serotonin levels drop, resulting in vagus nerve signaling issues, which may manifest in memory loss, among other long COVID symptoms.

Potential Avenues for Treating Long COVID Unveiled

“Healthcare providers have been depending on the personal accounts of patients to gauge the improvement of symptoms. Our study reveals that there could be biomarkers available for aligning patients with suitable treatments or clinical trials aimed at addressing the roots of their long COVID symptoms and for assessing their recovery more effectively,” stated Sara Cherry, PhD, a co-senior author and professor of Pathology and Laboratory Medicine.

The research team explored whether restoring tryptophan or serotonin levels could alleviate long COVID symptoms. They demonstrated in animal models that serotonin levels could be replenished and memory issues reversed through treatment with serotonin precursors or SSRIs.

“Evidence has suggested SSRIs might prevent long COVID, and our findings provide an opportunity for future studies to select patients with reduced serotonin for trials and measure their treatment response,” mentioned co-senior author Benjamin Abramoff, MD, MS, who is also the director of the Post-COVID Assessment and Recovery Clinic.

Moreover, exploring how viral infections affect tryptophan absorption opens doors for further research into tryptophan’s role in other body processes. While this study concentrated on serotonin, tryptophan is also a precursor to other vital metabolites like niacin, important for energy conversion from food, and melatonin, which regulates sleep patterns.

“Long COVID’s manifestation varies among individuals, and the causes of these symptom differences are not completely understood,” said Christoph Thaiss, PhD, an assistant professor of Microbiology and a co-senior author. “Our study allows for additional research to find out how many people with long COVID are impacted by the link between viral persistence, serotonin shortage, and vagus nerve dysfunction, and to identify more targets for treatment across the various symptoms patients face.”

For more details on the Post-COVID Assessment and Recovery Clinic and research on long COVID, please visit [link], or call 215-893-2668.

The study received partial funding from the PolyBio Research Foundation, the Penn Center for Research on Coronavirus and Other Emerging Pathogens, and several prestigious academic programs and foundations.

Frequently Asked Questions (FAQs) about long COVID serotonin link

More about long COVID serotonin link

• Perelman School of Medicine at the University of Pennsylvania
• Cell Journal Article on Long COVID and Serotonin
• CDC Long COVID Information
• Post-COVID Assessment and Recovery Clinic at Penn