E2 ModerateModerate confidencePEM unclearCross-SectionalPeer-reviewedReviewed
Comparable Immune Alterations and Inflammatory Signatures in ME/CFS and Long COVID.
Petrov, Steliyan, Bozhkova, Martina, Ivanovska, Mariya et al. · Biomedicines · 2025 · DOI
Quick Summary
This study compared immune system markers in people with ME/CFS and Long COVID to those of healthy individuals. Both patient groups showed similar immune problems: lower levels of protective immune cells and higher levels of inflammatory substances in their blood. The findings suggest that ME/CFS and Long COVID may involve very similar underlying immune dysfunction.
Why It Matters
This research provides objective evidence that ME/CFS and Long COVID share comparable immune dysfunction patterns, which could validate emerging theories about shared pathophysiological mechanisms and inform unified diagnostic and therapeutic approaches. For patients, this strengthens the biological basis of both conditions and supports the recognition of ME/CFS as a serious organic illness rather than primarily psychological.
Observed Findings
- Both ME/CFS and Long COVID groups showed significantly reduced total lymphocyte counts (ME/CFS: 2.472 × 10⁹/L; Long COVID: 2.051 × 10⁹/L) compared to healthy controls
- CD8+ T cell counts were substantially lower in both patient groups (ME/CFS: 0.394 × 10⁹/L; Long COVID: 0.404 × 10⁹/L) versus controls
- Natural killer (NK) cell counts were significantly reduced in both conditions (ME/CFS: 0.205 × 10⁹/L; Long COVID: 0.180 × 10⁹/L)
- Proinflammatory cytokines were elevated in both groups, including IL-6, TNF-α, IL-4, and IL-10
- No statistically significant differences in immune biomarkers were detected between ME/CFS and Long COVID patient groups
Inferred Conclusions
- ME/CFS and Long COVID display comparable immune and inflammatory profiles despite different etiopathogenic triggers, suggesting shared immunopathological mechanisms
- Both conditions are characterized by a specific pattern of immune dysregulation: reduced adaptive immunity (low T cells and NK cells) combined with heightened inflammatory cytokine production
- The immunological similarity between ME/CFS and Long COVID may justify unified clinical and research approaches to understanding these conditions
- These objective immune biomarker differences support the biological validity of both conditions as organic illnesses
Remaining Questions
What This Study Does Not Prove
This study does not establish causation—it demonstrates correlation between immune markers and disease status at a single time point. The cross-sectional design cannot determine whether immune changes cause symptoms or result from chronic illness. It also does not prove that these specific immune alterations are responsible for post-exertional malaise or other specific clinical features.
Tags
Symptom:Post-Exertional MalaiseCognitive DysfunctionPainFatigue
Biomarker:CytokinesBlood Biomarker
Phenotype:Long COVID OverlapInfection-Triggered
Method Flag:Weak Case DefinitionExploratory OnlyMixed Cohort
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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