Thierry et al. (2025)
- Authors: Alain R. Thierry, Tom Usher, Cynthia Sanchez, Simone Turner, Chantelle Venter, Brice Pastor, Maxine Waters, Anel Thompson, Alexia Mirandola, Ekaterina Pisareva, Corinne Prevostel, Gert J. Laubscher, Douglas B. Kell, Etheresia Pretorius
- Institutes: Montpellier Cancer Research Institute (IRCM), INSERM U1194, Montpellier, France, Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa, Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, UK
- Publisher: Journal of Medical Virology
- Link: DOI
Summary
This research provides a breakthrough explanation for the persistent fatigue and cognitive issues seen in Long COVID by showing that immune cells “wrap” microclots in protective DNA webs. By identifying these stubborn, reinforced structures, the study explains why the body cannot easily clear them on its own, leading to restricted blood flow in tiny vessels. These findings pave the way for more accurate diagnostic blood tests and new treatment strategies that target the specific components keeping these clots in circulation. This offers a tangible target for therapies that could finally restore normal oxygen delivery to tissues.
What was researched?
This study investigated the structural and quantitative association between circulating microclots and neutrophil extracellular traps (NETs) in patients with Long COVID.
Why was it researched?
Researchers aimed to determine if NETs, which are sticky “webs” of DNA released by immune cells, contribute to the formation and stabilization of stubborn microclots. Understanding this connection is vital for explaining why these clots persist and cause chronic symptoms like brain fog.
How was it researched?
The study compared blood plasma from 50 Long COVID patients and 38 healthy controls using imaging flow cytometry and fluorescence microscopy. Researchers tracked specific markers like myeloperoxidase and cell-free DNA to identify the presence of NETs within the blood. An AI model was also trained to distinguish between patient groups based on these microscopic features.
What has been found?
Microclots were nearly 20 times more abundant and significantly larger in Long COVID patients compared to healthy individuals. The study revealed that NETs are physically embedded within these microclots, acting as a structural “glue” that stabilizes them. This reinforced structure makes the clots highly resistant to the body’s natural breakdown processes. The combined presence of microclots and NETs provided a diagnostic accuracy of 91% for identifying Long COVID.
Discussion
A major strength of this work is the direct visualization of the physical interaction between immune-derived NETs and microclots. While the sample size is moderate, the high diagnostic accuracy and consistent structural findings lend significant weight to the thrombo-inflammatory theory of Long COVID. These results suggest that standard treatments might fail if they only target fibrin without addressing the stabilizing DNA webs.
Conclusion & Future Work
The findings suggest that NET-stabilized microclots are a central feature of Long COVID pathology. Future clinical trials should explore treatments that target both the clotting process and the immune webs, such as anticoagulants 💊 or DNA-degrading enzymes.