A groundbreaking study has pinpointed a microscopic culprit behind the debilitating fatigue, brain fog, and other persistent symptoms of long COVID: abnormal, sticky microclots embedded with neutrophil extracellular traps (NETs) in patients' blood. These microclots—tiny aggregates of clotting proteins—are small enough to obstruct the body's tiniest blood vessels (capillaries), restricting oxygen delivery to tissues and organs without triggering obvious large-scale clotting events. In long COVID patients, researchers observed a dramatic ~20-fold increase (median 19.7 times higher) in the number of these microclots compared to healthy controls, with the clots also tending to be larger. What sets this finding apart is the discovery that these microclots are structurally intertwined with NETs—web-like structures of DNA, enzymes (such as myeloperoxidase and neutrophil elastase), and proteins released by neutrophils (a type of white blood cell) to ensnare pathogens. Normally, NETs form temporarily and then dissolve, but in long COVID, they persist and become physically embedded within the microclots, creating highly resistant, "gummy" structures that evade the body's natural clot-breaking processes (fibrinolysis). This creates a chronic thromboinflammatory state, where blocked microcirculation and ongoing low-grade inflammation may sustain symptoms like exhaustion and cognitive impairment. The differences were so pronounced that machine learning models analyzing anonymized blood samples (via fluorescence microscopy for markers like ThT for amyloid-like structures, DNA stains, and MPO for NETs) could distinguish long COVID patients from healthy individuals with 91% accuracy—offering a potential objective biomarker for a condition that has long evaded reliable diagnosis through standard tests (e.g., normal D-dimer, PT/INR, or aPTT levels despite significant microclot burden). This work, led by teams including Prof. Etheresia Pretorius (Stellenbosch University) and Dr. Alain Thierry (Montpellier University), reframes long COVID as a tangible, blood-based disorder driven by dysregulated coagulation and innate immunity rather than vague "post-viral malaise." Targeting NETs or microclots—perhaps with therapies to degrade NETs or prevent their stabilization—could open doors to treating root causes instead of merely alleviating symptoms. [Thierry, A. R., Usher, T., Sanchez, C., Turner, S., Venter, C., Pastor, B., Waters, M., Thompson, A., Mirandola, A., Pisareva, E., Prevostel, C., Laubscher, G. J., Kell, D. B., & Pretorius, E. (2025). Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients. Journal of Medical Virology, 97(10), e70613. DOI: 10.1002/jmv.70613]