Research from the Perelman School of Medicine on the University of Pennsylvania has discovered a link between decreased serotonin ranges and sufferers affected by lengthy COVID – the persistent signs following a COVID-19 an infection.
Components of the SARS-CoV-2 virus stay within the intestine of some lengthy COVID sufferers, inflicting persistent irritation, vagus nerve dysfunction, and neurological signs.
Patients with lengthy COVID – the long-term signs like mind fog, fatigue, or reminiscence loss within the months or years following COVID-19 – can exhibit a discount in circulating ranges of the neurotransmitter serotonin, in accordance to new analysis printed on October 16 within the journal Cell. The research, led by researchers from the Perelman School of Medicine on the University of Pennsylvania, sheds new mild on the mechanisms of how persistent irritation after contracting the SARS-CoV-2 virus may cause long-term neurological symptoms.
According to the CDC, almost one in 5 American adults who had COVID-19 expertise signs of lengthy COVID. Most sufferers complain of mind fog, the lack to give attention to duties, reminiscence issues, common fatigue, and complications. The mechanisms that trigger lengthy COVID haven’t been studied in depth, and coverings which might be extensively efficient in lowering these long-term signs haven’t but been developed.
Research Insights on Long COVID Biology
“Many aspects of the basic biology underlying long COVID have remained unclear. As a result, we are lacking effective tools for the diagnosis and treatment of the disease,” mentioned senior creator, Maayan Levy, PhD, an assistant professor of Microbiology at Penn Medicine. “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 Pathway From Acute COVID-19 Infection to Long COVID
In a collaboration between Penn’s departments of Microbiology, Pathology and Laboratory Medicine, and Physical Medicine and Rehabilitations’ Post COVID Assessment and Recovery Clinic, researchers evaluated the consequences of lengthy COVID in blood and stool samples from varied medical research and in small animal fashions.
The researchers decided {that a} subset of sufferers with lengthy COVID had traces of the SARS-CoV-2 virus of their stool samples even months after acute COVID-19 an infection, which means that elements of the virus stay within the intestine of some sufferers lengthy after an infection. They discovered that this remaining virus, referred to as a viral reservoir, triggers the immune system to launch proteins that battle the virus, referred to as interferons. These interferons trigger irritation that reduces the absorption of the amino acid tryptophan within the gastrointestinal (GI) tract.
Tryptophan is a building block for a number of neurotransmitters, together with serotonin, which is primarily produced within the GI tract and carries messages between nerve cells within the mind and all through the body. It performs a key function in regulating reminiscence, sleep, digestion, wound therapeutic, and different capabilities that keep homeostasis inside the body. Serotonin can be an necessary regulator of the vagus nerve, a system of neurons that mediate the communication between the body and the mind.
The researchers discovered that when tryptophan absorption is lowered by persistent viral irritation, serotonin is depleted, main to disrupted vagus nerve signaling, which in flip may cause a number of of the signs related to lengthy COVID, akin to reminiscence loss.
Revealing Potential Treatment Avenues for Long COVID
“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,” mentioned co-senior creator, Sara Cherry, PhD, a professor of Pathology and Laboratory Medicine.
The authors took this perception one step additional, to establish if replenishing tryptophan or serotonin in sufferers who exhibit deficiencies might deal with lengthy COVID signs. They demonstrated that serotonin ranges could possibly be restored, and reminiscence impairment reversed, in small animal fashions by therapy with serotonin precursors or selective serotonin reuptake inhibitors (SSRIs).
“There has been some evidence to recommend that SSRIs could possibly be efficient in stopping lengthy COVID, and our analysis now presents a chance for future research to choose particular sufferers for a trial who exhibit depleted serotonin, and to find a way to measure response to therapy,” mentioned co-senior creator, Benjamin Abramoff, MD, MS, director of the Post-COVID Assessment and Recovery Clinic, and an assistant professor of Clinical Physical Medicine.
Furthermore, uncovering how viral an infection impacts the absorption of tryptophan presents extra alternatives for added analysis into the opposite processes that tryptophan influences. While this research targeted on serotonin, tryptophan is a building block for a lot of different necessary metabolites, like niacin, which helps the body flip food into vitality, and melatonin, a hormone that regulates circadian rhythms and sleep.
“Long COVID varies from patient to patient, and we don’t fully understand what causes the differences in symptoms,” mentioned co-senior creator, Christoph Thaiss, PhD, an assistant professor of Microbiology. “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.”
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, 16 October 2023, Cell.
DOI: 10.1016/j.cell.2023.09.013
For extra details about the Post-COVID Assessment and Recovery Clinic and Long COVID analysis, go to: https://www.pennmedicine.org/for-health-care-professionals/for-physicians/covid-information/post-covid19-assessment-and-recovery-clinic-at-penn, or name 215-893-2668.
The research was partly funded 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.
