A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications.
Kell, Douglas B, Laubscher, Gert Jacobus, Pretorius, Etheresia · The Biochemical journal · 2022 · DOI
Quick Summary
This study suggests that Long COVID may be caused by unusual blood clots called 'fibrin amyloid microclots' that form after COVID-19 infection. These tiny clots may block small blood vessels and reduce oxygen delivery throughout the body, which could explain many Long COVID symptoms like fatigue, brain fog, and breathing problems. The researchers found these microclots in Long COVID patients' blood and propose that special blood-thinning treatments might help dissolve them and relieve symptoms.
Why It Matters
This research provides a potential unifying biological mechanism for Long COVID and related post-viral syndromes like ME/CFS, which have historically lacked clear pathophysiological explanations. If microclots are validated as a central driver, it could transform diagnostic and therapeutic approaches for millions of patients whose symptoms remain unexplained by conventional medicine. Understanding shared mechanisms between Long COVID and ME/CFS may accelerate progress in both conditions.
Observed Findings
Extensive fibrin amyloid microclots are present in platelet-poor plasma of Long COVID patients, detectable via thioflavin T staining and fluorescence microscopy.
These microclots are relatively resistant to normal fibrinolysis (proteolysis), suggesting they persist in circulation.
Microclot formation may entrap other proteins and potentially trigger autoantibody production.
Preliminary observations suggest that anticoagulant therapy targeting microclots may correlate with symptom improvement.
The microclot phenotype resembles β-rich amyloid and prion-like structures found in other diseases.
Inferred Conclusions
Fibrin amyloid microclots represent a novel and measurable pathological feature of Long COVID distinct from acute COVID-19 pathology.
Microclot-induced capillary blockade and impaired oxygen delivery may explain the multisystem symptoms of Long COVID.
Fibrin amyloid microclots are a potentially actionable therapeutic target and warrant investigation as a diagnostic biomarker.
The mechanistic similarities between Long COVID and ME/CFS suggest these conditions may share underlying microvascular pathology.
Remaining Questions
Do fibrin amyloid microclots occur in ME/CFS patients, and if so, are they mechanistically similar to those in Long COVID?
What This Study Does Not Prove
This study does not prove that microclots cause Long COVID—it presents a hypothesis based on observational findings rather than experimental manipulation or causation studies. The preliminary anticoagulation data come from a small, uncontrolled report and do not establish efficacy or safety of 'triple therapy.' The findings cannot be generalized to all Long COVID patients, and microclots may be a consequence rather than a primary cause of disease. Long-term outcome data and controlled trials are needed before clinical recommendations can be made.