Al-Hakeim, Hussein Kadhem, Al-Rubaye, Haneen Tahseen, Almulla, Abbas F et al. · Journal of clinical medicine · 2023 · DOI
This study examined whether severe COVID-19 infection—particularly high fever and low oxygen levels—can trigger lasting fatigue, depression, and anxiety through inflammation and oxidative stress in the body. Researchers compared 86 long COVID patients with 39 healthy controls and found that about one-third of long COVID patients had very high signs of immune activation and cellular damage. The study suggests that the severity of initial COVID infection may predict who develops long-term symptoms through measurable changes in inflammatory markers.
ME/CFS and long COVID share overlapping physio-affective phenotypes, and this study provides measurable biomarkers that may explain symptom persistence, potentially enabling future stratification and targeted interventions. Understanding the neuroimmune mechanisms linking acute viral infection severity to chronic symptoms could inform both post-viral illness management and basic research into ME/CFS pathophysiology.
This cross-sectional study cannot prove that inflammation during acute infection *causes* long-term symptoms, only that markers are associated with symptoms months later. Biomarkers were measured at the long COVID timepoint, not during acute infection, so temporal relationships and causality remain unestablished. The study does not identify whether these inflammatory pathways are actively driving symptoms or are residual markers of past infection.
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
Al-Hakeim, Hussein Kadhem, Al-Rubaye, Haneen Tahseen, Almulla, Abbas F, Al-Hadrawi, Dhurgham Shihab, & Maes, Michael (2023). Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection.. Journal of clinical medicine. https://doi.org/10.3390/jcm12020511
BibTeX
@article{mecfsatlas-al-hakeim-2023-chronic-fatigue,
author = {Al-Hakeim, Hussein Kadhem and Al-Rubaye, Haneen Tahseen and Almulla, Abbas F and Al-Hadrawi, Dhurgham Shihab and Maes, Michael},
title = {Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection.},
journal = {Journal of clinical medicine},
year = {2023},
doi = {10.3390/jcm12020511},
note = {PubMed: 36675440},
url = {https://www.mecfsatlas.com/evidence/al-hakeim-2023-chronic-fatigue},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/al-hakeim-2023-chronic-fatigue
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