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Viral Persistence, Reduced Serotonin May Explain Long Covid Symptoms
Post-acute sequelae of COVID-19, commonly referred to as long COVID symptoms, are associated with reduced levels of the neurotransmitter serotonin, according to study findings published in the journal Cell.
The study presents a possible explanation for the long-term neurocognitive symptoms some patients experience after infection with SARS-CoV-2 and presents opportunities for treatment research.
“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,” said study senior author Maayan Levy, PhD, assistant professor of microbiology at the University of Pennsylvania in Philadelphia.
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Researchers investigated the effects of long COVID in blood and stool samples from various clinical studies and in small animal models. A subset of patients, they found, retained traces of SARS-CoV-2 in their stool months after acute infection.
The research team proposed that this viral reservoir prompts the immune system to release proteins called interferons to fight the virus. Inflammation results, which decreases absorption of the amino acid tryptophan — a building block of serotonin — in the gastrointestinal tract.
Serotonin, the team explained, is important for regulating memory, sleep, and other functions that promote homeostasis in the body. It also helps regulate the vagus nerve, a system of neurons that mediate communication between the body and the brain.
In short, the study suggests that persistent viral inflammation reduces tryptophan absorption, depletes serotonin, and impairs vagus nerve signaling, which in turn causes memory loss and other neurological symptoms.
“Clinicians treating patients with long COVID have been relying on personal reports from those patients to determine if their symptoms are improving. 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,” said co-senior author, Sara Cherry, PhD, professor of pathology and laboratory medicine at the University of Pennsylvania.
In small animal models, treatment with serotonin precursors or selective serotonin reuptake inhibitors (SSRIs) restored serotonin levels and reversed memory impairment, the team reported.
“There has been some evidence to suggest that SSRIs could be effective in preventing long COVID, and our research now presents an opportunity for future studies to select specific patients for a trial who exhibit depleted serotonin, and to be able to measure response to treatment,” said co-senior author, Benjamin Abramoff, MD, director of the Post-COVID Assessment and Recovery Clinic at the University of Pennsylvania.
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