Research from the Perelman School of Medicine at the University of Pennsylvania has found a link between decreased serotonin levels and patients suffering from long COVID – the lingering symptoms after a COVID-19 infection.
Components of the SARS-CoV-2 virus they remain in the gut of some long COVID patients, causing persistent inflammation, vagus nerve dysfunction, and neurological symptoms.
Long COVID patients: long-term symptoms such as brain fog, fatigue, or memory loss in the following months or years. COVID-19 – may present a reduction in circulating levels of the neurotransmitter serotonin, according to new research published October 16 in the journal Cell. The study, led by researchers at the Perelman School of Medicine at the University of Pennsylvania, sheds new light on the mechanisms by which persistent inflammation after contracting the SARS-CoV-2 virus can cause long-term neurological symptoms.
According to the CDC, nearly one in five American adults who have had COVID-19 experience symptoms of long COVID. Most patients complain of brain fog, inability to concentrate on tasks, memory problems, general fatigue, and headaches. The mechanisms that cause long COVID have not been studied in depth, and treatments have not yet been developed that are broadly effective in reducing these symptoms in the long term.
Research Perspectives on the Biology of Long COVID
“Many aspects of the basic biology underlying long COVID remain unclear. As a result, we lack effective tools for diagnosing and treating the disease,” said senior author Maayan Levy, PhD, assistant professor of Microbiology at Penn Medicine. “Our findings may not only help unravel some of the mechanisms that contribute to long COVID, but also provide us with biomarkers that can help doctors diagnose patients and objectively measure their response to individual treatments.”
The path from acute COVID-19 infection to long COVID
In a collaboration between Penn’s departments of Microbiology, Pathology, and Laboratory Medicine, and the Physical Medicine and Rehabilitation Post-COVID Assessment and Recovery Clinic, researchers evaluated the effects of long COVID in blood and stool samples from several clinical studies. and in small animal models.
The researchers determined that a subset of long COVID patients had traces of the SARS-CoV-2 virus in their stool samples even months after acute COVID-19 infection, suggesting that virus components remain in the intestine of some patients much later. infection. They discovered that this remaining virus, called the viral reservoir, causes the immune system to release virus-fighting proteins called interferons. These interferons cause inflammation that reduces absorption of the amino acid. acid tryptophan in the gastrointestinal (GI) tract.
Tryptophan is a building block of several neurotransmitters, including serotonin, which is produced primarily in the gastrointestinal tract and carries messages between nerve cells in the brain and throughout the body. It plays a key role in regulating memory, sleep, digestion, wound healing, and other functions that maintain homeostasis within the body. Serotonin is also an important regulator of the vagus nerve, a system of neurons that mediates communication between the body and the brain.
Researchers found that when tryptophan absorption is reduced due to persistent viral inflammation, serotonin is depleted, leading to impaired vagus nerve signaling, which in turn can cause several of the symptoms associated with COVID. prolonged, such as memory loss.
Revealing potential treatment avenues for long COVID
“Doctors treating patients with long COVID have relied on self-reports from those patients to determine whether their symptoms are improving. “Now, our research shows that there are biomarkers we can use to match patients with treatments or clinical trials that address the specific causes of their long COVID symptoms and more effectively assess their progress,” said co-lead author Sara Cherry. . , PhD, professor of Pathology and Laboratory Medicine.
The authors took this idea a step further to identify whether replenishing tryptophan or serotonin in patients who are deficient could treat long COVID symptoms. They showed that serotonin levels could be restored and memory impairment reversed in small animal models by treatment with serotonin precursors or selective serotonin reuptake inhibitors (SSRIs).
“There has been some evidence to suggest that SSRIs might be effective in preventing long COVID, and our research now presents an opportunity for future studies to select specific patients for a trial who have decreased serotonin and can measure response to treatment.” . said co-senior author Benjamin Abramoff, MD, MS, director of the Post-COVID Assessment and Recovery Clinic and assistant professor of Clinical Physical Medicine.
Furthermore, discovering how viral infection affects tryptophan absorption presents further opportunities for additional research into other processes influenced by tryptophan. While this study focused on serotonin, tryptophan is a building block of many other important metabolites, including niacin, which helps the body convert food into energy, and melatonin, a hormone that regulates circadian rhythms and sleep. dream.
“Long COVID varies from patient to patient and we do not fully understand what causes the differences in symptoms,” said co-senior author Christoph Thaiss, PhD, assistant professor of Microbiology. “Our study provides a unique opportunity to conduct further research to determine how many people with long COVID are affected by the pathway linking viral persistence, serotonin deficiency, and vagus nerve dysfunction and to discover additional targets for treatments in different settings.” symptoms experienced by patients. “
Reference: “Serotonin reduction in post-acute sequelae of viral infection” by Andrea C. Wong, Ashwarya S. Devason, Iboro C. Umana, Timothy O. Cox, Lenka Dohnalová, Lev Litichevskiy, Jonathan Perla, Patrick Lundgren, Zienab Etwebi, Luke T. Izzo, Jihee Kim, Monika Tetlak, Hélène C. Descamps, Simone L. Park, Stephen Wisser, Aaron D. McKnight, Ryan D. Pardy, Junwon Kim, Niklas Blank, Shaan Patel, Katharina Thum, Sydney Mason, Jean – Christophe Beltra, Michaël F. Michieletto, Shin Foong Ngiow, Brittany M. Miller, Megan J. Liou, Bhoomi Madhu, Oxana Dmitrieva-Posocco, Alex S. Huber, Peter Hewins, Christopher Petucci, Candice P. Chu, Gwen Baraniecki-Zwil , Leila B. Giron, Amy E. Baxter, Allison R. Greenplate, Charlotte Kearns, Kathleen Montone, Leslie A. Litzky, Michael Feldman, Jorge Henao-Mejia, Boris Striepen, Holly Ramage, Kellie A. Jurado, Kathryn E. Wellen , Una O’Doherty, Mohamed Abdel-Mohsen, Alan L. Landay, Ali Keshavarzian, Timothy J. Henrich, Steven G. Deeks, Michael J. Peluso, Nuala J. Meyer, E. John Wherry, Benjamin A. Abramoff, Sara Cherry, Christoph A. Thaiss and Maayan Levy, October 16, 2023, Cell.
DOI: 10.1016/j.cell.2023.09.013
For more information about the Post-COVID Assessment and Recovery Clinic and long COVID research, visit: https://www.pennmedicine.org/for-health-care-professionals/for-physicians/covid-information/post -covid19-assessment -and-recovery-clinic-at-penn, or call 215-893-2668.
The study was funded in part by the PolyBio Research Foundation, the Penn Center for Research on Coronavirus and other emerging pathogens, the Pew Biomedical Scholar program, the Searle Scholars program, and the Burroughs Wellcome Fund.
