[Long COVID - neurological or somatoform disease?].

Evidence Atlas

Tényi, Dalma, Tényi, Tamás, Janszky, József · Ideggyogyaszati szemle · 2024 · DOI

Quick Summary

This study reviews research on long COVID to understand what causes its main symptoms like extreme fatigue, pain, and brain fog. Doctors are still debating whether long COVID is primarily a brain/nerve disease, a whole-body illness affecting multiple systems, or a condition where the brain becomes overly sensitive to signals. The researchers found that long COVID shares many similarities with ME/CFS and other hard-to-diagnose conditions, but no single test currently exists to confirm long COVID diagnosis.

Why It Matters

This review is crucial because it clarifies the current state of long COVID research and its striking similarities to ME/CFS—a condition that has long struggled for recognition and understanding. By synthesizing competing theories, this work helps patients and clinicians understand why long COVID remains diagnostically challenging and emphasizes the urgent need for biomarker discovery. Clear understanding of disease mechanisms is essential for developing targeted, effective treatments for both conditions.

Observed Findings

Three main theoretical frameworks for long COVID pathomechanism are documented in the literature: neurological, systemic, and psychoneuroimmunological models.
Long COVID shares significant clinical overlap with ME/CFS, Gulf War syndrome, chronic Lyme disease, and somatic symptom disorder.
No reproducible, disease-specific biomarker has been identified for long COVID despite intensive research.
The most common long COVID symptoms are fatigue, diffuse pain, post-exertional malaise, and cognitive impairment (brain fog).
Long COVID is defined as persistent symptoms lasting at least 2 months following confirmed or suspected SARS-CoV-2 infection.

Inferred Conclusions

Long COVID pathomechanism remains unknown, likely involving complex interactions between direct viral effects, immune dysregulation, and central sensitization.
The nonspecific symptom profile and diagnostic uncertainty in long COVID parallels longstanding challenges in ME/CFS diagnosis and classification.
Elucidating long COVID's true etiology is essential for developing appropriate, evidence-based therapeutic interventions.
The absence of disease-specific biomarkers suggests that current diagnostic frameworks may be inadequate and that novel research approaches are needed.

Remaining Questions

What This Study Does Not Prove

This review does not prove which pathomechanism is correct—these remain competing theories without definitive evidence favoring one over the others. The study cannot identify disease-specific biomarkers itself; it only confirms that none have been reliably validated to date. The overlaps identified with ME/CFS suggest common mechanisms but do not establish whether long COVID and ME/CFS are identical conditions or distinct entities with shared features.

Metadata

DOI: 10.18071/isz.77.0397
PMID: 39635815
Review status: Editor reviewed
Evidence level: Established evidence from major reviews, guidelines, or evidence maps
Last updated: 12 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 →

Evidence Atlas

[Long COVID - neurological or somatoform disease?].

Quick Summary

Why It Matters

Observed Findings

Inferred Conclusions

Remaining Questions

What This Study Does Not Prove

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