E3 PreliminaryPreliminaryPEM not requiredObservationalPeer-reviewedMachine draft
Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19.
Kwon, Ji-Soo, Chang, Euijin, Jang, Hyeon Mu et al. · The Korean journal of internal medicine · 2025 · DOI
Quick Summary
After COVID-19, some people develop long-lasting symptoms like fatigue, brain fog, and difficulty exercising—a condition called long COVID or PASC. This study measured immune system markers (called cytokines) in the blood of 79 people and found that certain symptoms were linked to higher levels of specific immune proteins, suggesting the immune system may stay overactive in some long COVID patients.
Why It Matters
This study helps identify biological mechanisms underlying long COVID symptoms, which may parallels to ME/CFS pathophysiology including post-exertional malaise and immune dysregulation. Understanding cytokine patterns could inform targeted therapeutic approaches and validate symptom heterogeneity as reflecting distinct but related immune pathways.
Observed Findings
- Fatigue was the most frequent symptom, followed by post-exertional malaise, chronic cough, thirst, and brain fog.
- Post-exertional malaise, gastrointestinal symptoms, chest pain, brain fog, abnormal movement, and palpitation were significantly associated with elevated IL-10, VEGF, and pro-inflammatory cytokines (IL-1β, IL-6, IL-8, MIP-1α, MIG, granzyme A, CX3CL1).
- Chronic cough, dizziness, dyspnea, and hair loss showed no significant cytokine associations.
- Symptom clusters affecting different organ systems shared common elevated cytokine profiles, suggesting overlapping pathophysiology.
Inferred Conclusions
- T-cell recruitment, thrombosis, and increased vascular permeability may represent shared pathophysiological mechanisms linking heterogeneous PASC symptom clusters.
- Cytokine signatures may stratify PASC patients and guide mechanistically-informed treatment strategies.
- Heterogeneity of PASC symptoms may reflect organ-specific manifestations of common immune dysregulation rather than entirely distinct etiologies.
Remaining Questions
- Why do some symptoms (cough, dyspnea, dizziness) not correlate with measured cytokine elevations—are different immune markers involved, or are these symptoms driven by non-immune mechanisms?
- Do elevated cytokines persist beyond 6 months, and do they predict symptom duration or resolution?
What This Study Does Not Prove
This study does not prove that cytokine elevation *causes* these symptoms—only that they occur together (correlation, not causation). It does not establish whether elevated cytokines are pathogenic, protective, or merely epiphenomenal. Additionally, findings are limited to the acute-to-subacute phase (1–6 months) and may not apply to chronic long COVID or ME/CFS patients.
Tags
Symptom:Post-Exertional MalaiseCognitive DysfunctionFatigue
Biomarker:CytokinesBlood Biomarker
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:PEM Not DefinedWeak Case DefinitionNo ControlsSmall SampleExploratory OnlyMixed Cohort
Metadata
- DOI
- 10.3904/kjim.2024.217
- PMID
- 40635493
- Review status
- Machine draft
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 8 April 2026
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 →
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