Title: Study Reveals Link Between Decreased Serotonin Levels and Long COVID Symptoms
Subtitle: Researchers at the University of Pennsylvania shed light on the mechanisms of persistent neurological symptoms after COVID-19 infection
Date: October 17, 2023
A new study conducted by researchers at the University of Pennsylvania’s Perelman School of Medicine has discovered a connection between decreased serotonin levels and patients suffering from long COVID. The findings shed new light on the underlying mechanisms of persistent neurological symptoms experienced by individuals even months or years after recovering from COVID-19.
Long COVID, also known as post-acute sequelae of viral infection (PASC), is characterized by a range of persistent symptoms such as brain fog, fatigue, memory loss, and headaches. According to the Centers for Disease Control and Prevention (CDC), nearly one in five American adults who had COVID-19 experience these long-term symptoms, but the precise causes have not been extensively studied.
The research, published in the journal Cell, involved the evaluation of blood and stool samples from patients with long COVID and small animal models. The researchers discovered that a subset of patients had traces of the SARS-CoV-2 virus in their stool samples even months after the acute COVID-19 infection. This indicates that viral components remain in the gut, causing persistent inflammation.
The presence of the virus in the gut triggers the immune system to release proteins called interferons. These interferons promote inflammation, which impairs the absorption of tryptophan, an essential amino acid in the gastrointestinal (GI) tract. Tryptophan is a precursor for serotonin, a neurotransmitter involved in various bodily functions, including memory, sleep, and digestion.
The researchers found that when tryptophan absorption is reduced due to persistent viral inflammation, serotonin levels decrease, leading to disrupted signaling in the vagus nerve. The vagus nerve is responsible for communication between the body and the brain and is an important regulator of various bodily functions.
Lead author Dr. Maayan Levy explained, “Our findings may not only help to untangle some of the mechanisms that contribute to long COVID but also provide us with biomarkers that can help clinicians diagnose patients and objectively measure their response to individual treatments.”
The study also revealed potential avenues for treating long COVID symptoms. The researchers demonstrated that replenishing tryptophan or serotonin levels in animal models could reverse memory impairment. Selective serotonin reuptake inhibitors (SSRIs), commonly used as antidepressant medications, were found to restore serotonin levels in the models.
Co-senior author Dr. Sara Cherry emphasized the significance of these findings, stating, “Now, our research shows that there are biomarkers we may be able to use to match patients to treatments or clinical trials that address the specific causes of their long COVID symptoms, and more effectively assess their progress.”
The study opens up opportunities for further research into the impact of viral infection on tryptophan absorption and other associated processes. Tryptophan is also involved in the production of niacin and melatonin, both of which have important roles in energy metabolism and sleep regulation, respectively.
Co-senior author Dr. Christoph Thaiss added, “Our study 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.”
The study was partly funded by several organizations, including the PolyBio Research Foundation, the Pew Biomedical Scholars Program, and the Burroughs Wellcome Fund. The researchers hope that their findings will lead to the development of more effective diagnostic tools and targeted treatments for individuals suffering from long COVID.
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Reference:
Andrea C. Wong, et al. “Serotonin reduction in post-acute sequelae of viral infection,” Cell, October 16, 2023. DOI: 10.1016/j.cell.2023.09.013