Serotonin reduction in post-acute sequelae of viral infection.

Humans COVID-19 / complications Disease Progression Inflammation Post-Acute COVID-19 Syndrome / blood Serotonin / blood Virus Diseases
Long COVID PASC neurocognitive symptoms platelets post-viral syndromes serotonin thrombocytopenia type I interferons vagus nerve viral persistence

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
26 10 2023
Historique:
received: 04 08 2022
revised: 27 07 2023
accepted: 13 09 2023
medline: 30 10 2023
pubmed: 18 10 2023
entrez: 17 10 2023
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.cell.2023.09.013 PMID: 37848036
pubmed: 37848036
pii: S0092-8674(23)01034-6
doi: 10.1016/j.cell.2023.09.013
pii:
doi:

Substances chimiques

Serotonin 333DO1RDJY

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

4851-4867.e20

Subventions

Organisme : NCI NIH HHS
ID : P30 CA016520
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI045008
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI055400
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL160065
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI141393
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK123733
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA029859
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141003
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI158013
Pays : United States
Organisme : NIA NIH HHS
ID : DP2 AG067492
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK050306
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR069589
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK019525
Pays : United States
Organisme : NIA NIH HHS
ID : DP2 AG067511
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests E.J.W. is an advisor for Danger Bio, Janssen, New Limit, Marengo, Pluto Immunotherapeutics Related Sciences, Rubius Therapeutics, Santa Ana Bio, Synthekine, and Surface Oncology. E.J.W. is a founder of and holds stock in Surface Oncology, Danger Bio, and Arsenal Biosciences. N.J.M. reports consulting fees from Endpoint Health Inc and AstraZeneca and receives funding from Quantum Leap Healthcare Collaborative outside of the published work.

Auteurs

Andrea C Wong (AC)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Ashwarya S Devason (AS)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Iboro C Umana (IC)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Timothy O Cox (TO)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Lenka Dohnalová (L)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Molecular Bio Science, Goethe University Frankfurt, Frankfurt am Main, Germany.

Lev Litichevskiy (L)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jonathan Perla (J)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Patrick Lundgren (P)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Zienab Etwebi (Z)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Luke T Izzo (LT)

Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.

Jihee Kim (J)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Monika Tetlak (M)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Hélène C Descamps (HC)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Simone L Park (SL)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Stephen Wisser (S)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Aaron D McKnight (AD)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Ryan D Pardy (RD)

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Junwon Kim (J)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Niklas Blank (N)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Shaan Patel (S)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Katharina Thum (K)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Sydney Mason (S)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jean-Christophe Beltra (JC)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Michaël F Michieletto (MF)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.

Shin Foong Ngiow (SF)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Brittany M Miller (BM)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Megan J Liou (MJ)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Bhoomi Madhu (B)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Oxana Dmitrieva-Posocco (O)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Alex S Huber (AS)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Peter Hewins (P)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Christopher Petucci (C)

Metabolomics Core, Penn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA, USA.

Candice P Chu (CP)

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Gwen Baraniecki-Zwil (G)

Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Leila B Giron (LB)

The Wistar Institute, Philadelphia, PA, USA.

Amy E Baxter (AE)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Allison R Greenplate (AR)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Charlotte Kearns (C)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Kathleen Montone (K)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Leslie A Litzky (LA)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Michael Feldman (M)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Jorge Henao-Mejia (J)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.

Boris Striepen (B)

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Holly Ramage (H)

Department of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

Kellie A Jurado (KA)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Kathryn E Wellen (KE)

Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA.

Una O'Doherty (U)

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Mohamed Abdel-Mohsen (M)

The Wistar Institute, Philadelphia, PA, USA.

Alan L Landay (AL)

Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA.

Ali Keshavarzian (A)

Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA; Rush Center for Integrated Microbiome and Chronobiology Research, Chicago, IL, USA.

Timothy J Henrich (TJ)

Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA.

Steven G Deeks (SG)

Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Michael J Peluso (MJ)

Division of HIV, Infectious Diseases, and Global Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Nuala J Meyer (NJ)

Division of Pulmonary and Critical Care Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

E John Wherry (EJ)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Benjamin A Abramoff (BA)

Department of Physical Medicine and Rehabilitation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: benjamin.abramoff@pennmedicine.upenn.edu.

Sara Cherry (S)

Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: cherrys@pennmedicine.upenn.edu.

Christoph A Thaiss (CA)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Institute for Obesity, Diabetes and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: thaiss@pennmedicine.upenn.edu.

Maayan Levy (M)

Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: maayanle@pennmedicine.upenn.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Serotonin reduction in post-acute sequelae of...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Serotonin reduction in post-acute sequelae of...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Serotonin reduction in post-acute sequelae of...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Inflammation › Serotonin reduction in post-acute sequelae of...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie chronique › Troubles post-infectieux › Syndrome de post-COVID-19 › Serotonin reduction in post-acute sequelae of...
questionsmedicales.fr › Facteurs biologiques › Médiateurs de l'inflammation › Autacoïdes › Sérotonine › Serotonin reduction in post-acute sequelae of...
questionsmedicales.fr › Infection › Maladies virales › Serotonin reduction in post-acute sequelae of...