Guo, Lihui, Appelman, Brent, Mooij-Kalverda, Kirsten et al. · EBioMedicine · 2023 · DOI
This study found that people with long-COVID have persistent activity of an enzyme called IDO2 in their blood cells and brain tissue, months or years after initial infection. This enzyme breaks down tryptophan (an amino acid) into other compounds that may trigger cellular stress and energy problems. The researchers also discovered that blocking a specific receptor (called AHR) could stop this process in laboratory tests, suggesting a potential treatment target.
This research identifies a potential biological mechanism underlying PASC/long-COVID—prolonged activation of a tryptophan-degrading enzyme that persists long after viral clearance. Discovery that AHR antagonists can suppress this pathway in vitro opens a novel therapeutic avenue that could be tested to alleviate fatigue, post-exertional malaise, and cognitive dysfunction in ME/CFS and PASC populations.
This study does not prove that IDO2 activity directly causes PASC symptoms, only that it is present and correlates with cellular stress markers. It does not establish whether AHR antagonists would be effective or safe in patients (only ex vivo efficacy was shown). The cross-sectional design cannot determine whether IDO2 activation is a primary driver or a secondary consequence of immune dysregulation.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Guo, Lihui, Appelman, Brent, Mooij-Kalverda, Kirsten, Houtkooper, Riekelt H, van Weeghel, Michel, Vaz, Frédéric M, et al. (2023). Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection.. EBioMedicine. https://doi.org/10.1016/j.ebiom.2023.104729
BibTeX
@article{mecfsatlas-guo-2023-prolonged-indoleamine,
author = {Guo, Lihui and Appelman, Brent and Mooij-Kalverda, Kirsten and Houtkooper, Riekelt H and van Weeghel, Michel and Vaz, Frédéric M and Dijkhuis, Annemiek and Dekker, Tamara and Smids, Barbara S and Duitman, Jan Willem and Bugiani, Marianna and Brinkman, Paul and Sikkens, Jonne J and Lavell, H A Ayesha and Wüst, Rob C I and van Vugt, Michèle and Lutter, René and Amsterdam UMC COVID-19 Biobank study Group},
title = {Prolonged indoleamine 2,3-dioxygenase-2 activity and associated cellular stress in post-acute sequelae of SARS-CoV-2 infection.},
journal = {EBioMedicine},
year = {2023},
doi = {10.1016/j.ebiom.2023.104729},
note = {PubMed: 37506544},
url = {https://www.mecfsatlas.com/evidence/guo-2023-prolonged-indoleamine},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/guo-2023-prolonged-indoleamine
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