Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection
eBioMedicine, Volume 94, Article 104729, Year 2023
Notification
URL copied to clipboard!
Description
Background: Post-acute sequela of SARS-CoV-2 infection (PASC) encompass fatigue, post-exertional malaise and cognitive problems. The abundant expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-2 (IDO2) in fatal/severe COVID-19, led us to determine, in an exploratory observational study, whether IDO2 is expressed and active in PASC, and may correlate with pathophysiology. Methods: Plasma or serum, and peripheral blood mononuclear cells (PBMC) were obtained from well-characterized PASC patients and SARS-CoV-2-infected individuals without PASC. We assessed tryptophan and its degradation products by UPLC-MS/MS. IDO2 activity, its potential consequences, and the involvement of the aryl hydrocarbon receptor (AHR) in IDO2 expression were determined in PBMC from another PASC cohort by immunohistochemistry (IHC) for IDO2, IDO1, AHR, kynurenine metabolites, autophagy, and apoptosis. These PBMC were also analyzed by metabolomics and for mitochondrial functioning by respirometry. IHC was also performed on autopsy brain material from two PASC patients. Findings: IDO2 is expressed and active in PBMC from PASC patients, as well as in brain tissue, long after SARS-CoV-2 infection. This is paralleled by autophagy, and in blood cells by reduced mitochondrial functioning, reduced intracellular levels of amino acids and Krebs cycle-related compounds. IDO2 expression and activity is triggered by SARS-CoV-2-infection, but the severity of SARS-CoV-2-induced pathology appears related to the generated specific kynurenine metabolites. Ex vivo, IDO2 expression and autophagy can be halted by an AHR antagonist. Interpretation: SARS-CoV-2 infection triggers long-lasting IDO2 expression, which can be halted by an AHR antagonist. The specific kynurenine catabolites may relate to SARS-CoV-2-induced symptoms and pathology. Funding: None. © 2023 The Author(s)
Authors & Co-Authors
Vaz, Frédéric M.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Dijkhuis, Annemiek
Netherlands, Amsterdam
Universiteit Van Amsterdam
Duitman, Jan Willem
Netherlands, Amsterdam
Universiteit Van Amsterdam
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Bugiani, Marianna
Netherlands, Amsterdam
Vrije Universiteit Amsterdam
Brinkman, Paul
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
van Vugt, Michèle V.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Lutter, René
Netherlands, Amsterdam
Universiteit Van Amsterdam
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
van Baarle, Frank E.F.P.
Unknown Affiliation
Bogaard, H. J.
Unknown Affiliation
Bonta, Peter I.
Unknown Affiliation
Bos, Lieuwe D.J.
Unknown Affiliation
de Brabander, Justin
Unknown Affiliation
de Bree, Godelieve J.
Unknown Affiliation
de Bruin, Sanne
Unknown Affiliation
Geerlings, Suzanne Eugenie
Unknown Affiliation
Goorhuis, Abram
Unknown Affiliation
Grobusch, Martín Peter
Unknown Affiliation
Hagens, Laura A.
Unknown Affiliation
Harris, Vanessa C.
Unknown Affiliation
Hermans, S. M.
Unknown Affiliation
Heunks, Leo M.A.
Unknown Affiliation
Hollmann, Markus Wiersma
Unknown Affiliation
Horn, Janneke
Unknown Affiliation
Hovius, Joppe Willem R.
Unknown Affiliation
de Jong, Menno Douwe
Unknown Affiliation
Lim, Endry H.T.
Unknown Affiliation
Nossent, Esther J.
Unknown Affiliation
Peters, Edgar J.
Unknown Affiliation
van der Poll, Tom
Unknown Affiliation
Prins, Jan M.
Unknown Affiliation
Sigaloff, Kim Catherina Eve
Unknown Affiliation
Slim, Marleen A.
Unknown Affiliation
Smeele, Patrick J.
Unknown Affiliation
Smit, Marry R.
Unknown Affiliation
Tuinman, Pieter Roel
Unknown Affiliation
van der Valk, Marc
Unknown Affiliation
Veelo, Denise Petra
Unknown Affiliation
van Vught, Lonneke Alette V.
Unknown Affiliation
Zwinderman, Aeilko Having Koos
Unknown Affiliation
Brouwer, Matthijs C.
Unknown Affiliation
Wiersinga, Willem Joost
Unknown Affiliation
Vlaar, Alexander Petrus Johannes
Unknown Affiliation
van de Beek, Diederik V.D.
Unknown Affiliation
Statistics
Citations: 2
Authors: 43
Affiliations: 6
Identifiers
Doi:
10.1016/j.ebiom.2023.104729
ISSN:
23523964
Research Areas
Cancer
Covid
Study Design
Cohort Study
Exploratory Study