Document Type
Article
Publication Date
10-26-2023
Abstract
Post-acute sequelae of COVID-19 (PASC, "Long COVID") pose a significant global health challenge. The pathophysiology is unknown, and no effective treatments have been found to date. Several hypotheses have been formulated to explain the etiology of PASC, including viral persistence, chronic inflammation, hypercoagulability, and autonomic dysfunction. Here, we propose a mechanism that links all four hypotheses in a single pathway and provides actionable insights for therapeutic interventions. We find that PASC are associated with serotonin reduction. Viral infection and type I interferon-driven inflammation reduce serotonin through three mechanisms: diminished intestinal absorption of the serotonin precursor tryptophan; platelet hyperactivation and thrombocytopenia, which impacts serotonin storage; and enhanced MAO-mediated serotonin turnover. Peripheral serotonin reduction, in turn, impedes the activity of the vagus nerve and thereby impairs hippocampal responses and memory. These findings provide a possible explanation for neurocognitive symptoms associated with viral persistence in Long COVID, which may extend to other post-viral syndromes.
Recommended Citation
Wong, Andrea; Devason, Ashwarya; Umana, Iboro; Cox, Timothy; Dohnalová, Lenka; Litichevskiy, Lev; Perla, Jonathan; Lundgren, Patrick; Etwebi, Zienab; Izzo, Luke; Kim, Jihee; Tetlak, Monika; Descamps, Hélène; Park, Simone; Wisser, Stephen; McKnight, Aaron; Pardy, Ryan; Kim, Junwon; Blank, Niklas; Patel, Shaan; Thum, Katharina; Mason, Sydney; Beltra, Jean-Christophe; Michieletto, Michaël; Ngiow, Shin Foong; Miller, Brittany; Liou, Megan; Madhu, Bhoomi; Dmitrieva-Posocco, Oxana; Huber, Alex; Hewins, Peter; Petucci, Christopher; Chu, Candice; Baraniecki-Zwil, Gwen; Giron, Leila; Baxter, Amy; Greenplate, Allison; Kearns, Charlotte; Montone, Kathleen; Litzky, Leslie; Feldman, Michael; Henao-Mejia, Jorge; Striepen, Boris; Ramage, Holly; Jurado, Kellie; Wellen, Kathryn; O'Doherty, Una; Abdel-Mohsen, Mohamed; Landay, Alan L; Keshavarzian, Ali; Henrich, Timothy; Deeks, Steven; Peluso, Michael; Meyer, Nuala; Wherry, E. John; Abramoff, Benjamin; Cherry, Sara; Thaiss, Christoph; and Levy, Maayan, "Serotonin Reduction in Post-acute Sequelae of Viral Infection" (2023). Department of Microbiology and Immunology Faculty Papers. Paper 179.
https://jdc.jefferson.edu/mifp/179
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
PubMed ID
37848036
Language
English
Included in
Pathological Conditions, Signs and Symptoms Commons, Therapeutics Commons, Virus Diseases Commons
Comments
This article is the author's final published version in Cell, Volume 186, Issue 22, October 2023, Pages 4851 - 4867.e20.
The published version is available at https://doi.org/10.1016/j.cell.2023.09.013.
Copyright © 2023 The Authors