E3 PreliminaryPreliminaryPEM unclearReview-NarrativePeer-reviewedMachine draft
Are fibrinaloid microclots a cause of autoimmunity in Long Covid and other post-infection diseases?
Kell, Douglas B, Pretorius, Etheresia · The Biochemical journal · 2023 · DOI
Quick Summary
This study proposes that in Long COVID and other post-infection diseases, a blood protein called fibrinogen can fold into an abnormal shape that forms sticky clots called fibrinaloids. These unusual clots may trigger the immune system to attack the body's own tissues (autoimmunity) because the abnormal folding creates new structures the immune system doesn't recognize. The authors suggest this process is similar to what happens in prion diseases and other protein-misfolding conditions.
Why It Matters
Understanding whether fibrinaloid microclots initiate autoimmunity could explain both the clotting abnormalities and immune dysregulation observed in ME/CFS and Long COVID. If fibrinaloid formation is indeed a primary mechanism, it could open new avenues for prevention and targeted treatment. This hypothesis bridges multiple disease mechanisms and may help unify observations across post-infection syndromes.
Observed Findings
- Fibrinogen can polymerize into an amyloid-like fibrin form (fibrinaloids) that resists normal breakdown and occludes microcapillaries
- Fibrinaloids bind and entrap other molecules and stain positive for amyloid markers
- Anomalous fibrin polymerization generates novel protein conformations not normally presented to the immune system
- The structure of fibrinaloid clots likely depends on pre-existing small molecules and metal ions bound to fibrinogen before polymerization
Inferred Conclusions
- Fibrinaloid formation generates cryptic epitopes that breach immune tolerance and drive autoantibody production
- The mechanism of fibrinaloid genesis shares principles with prion and classical amyloid diseases, including multiple stable conformations and seeding propagation
- Prevention of fibrinaloid formation or early intervention in the polymerization process may reduce or prevent post-infection autoimmunity
Remaining Questions
- What specific small molecules and metal ions promote or prevent fibrinaloid polymerization in Long COVID?
- Is fibrinaloid formation the primary initiating event in post-infection autoimmunity, or a secondary consequence of other immune or endothelial dysfunction?
- Can fibrinaloid-directed therapeutic interventions (e.g., promoting fibrinolysis or chelating relevant metal ions) reverse established autoimmunity?
What This Study Does Not Prove
This review does not provide direct experimental or clinical evidence that fibrinaloids cause autoimmunity in Long COVID patients—it presents a mechanistic hypothesis. The study does not demonstrate that fibrinaloid formation is necessary and sufficient for disease, nor does it establish the relative contribution of this mechanism compared to other factors. Correlation between fibrinaloid presence and autoantibody generation in human disease remains to be firmly established.
Tags
Biomarker:AutoantibodiesBlood Biomarker
Phenotype:Infection-TriggeredLong COVID Overlap
Method Flag:Exploratory Only
Metadata
- DOI
- 10.1042/BCJ20230241
- PMID
- 37584410
- 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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