“I’ve taken nattokinase, tried anticoagulants, changed my diet. My bloodwork improved but my body still feels broken.”
Many people living with Long COVID resonate with this story. And many have found genuine benefit from therapies targeting microclots those stubborn, amyloid-rich fibrin clots that block microcirculation and drive symptoms like fatigue, brain fog, and breathlessness.
But the latest research in 2024 and 2025 is pointing to something even broader: vascular injury beyond clotting. That includes capillary rarefaction and endothelial cell ageing processes that could be silently stealing oxygen and resilience from people’s bodies, even when clots are being addressed.
Microclots Matter, But They’re Not the Whole Story
The microclot hypothesis has transformed the conversation around Long COVID. Groundbreaking work by researchers like Prof. Resia Pretorius has shown that many people with persistent symptoms have clotting proteins misfolded into amyloid, making them sticky and resistant to normal breakdown.
These microclots reduce oxygen delivery, trigger inflammation, and help explain why people feel “starved of energy” even after normal cardiopulmonary test results. Many patients using enzymes or low-dose anticoagulants report some degree of improvement.
But despite that, not everyone gets better. And not all Long COVID symptoms are fully explained by clotting alone. That’s why researchers are now widening the lens.
Capillary Rarefaction: Shrinking the Oxygen Supply
Capillaries are the body’s most delicate vessels only one red blood cell wide. They’re the interface between blood and tissue, where oxygen and nutrients are delivered to muscles, nerves, and organs.
In Long COVID, growing evidence suggests that these capillaries are being lost or damaged. This is called capillary rarefaction and it reduces the total surface area for oxygen exchange. The result? Even with “good blood flow,” your body can’t fully oxygenate itself, especially under stress or exertion.
Early studies from 2025 show reduced capillary density in skeletal muscle and impaired oxygen extraction, even in people with otherwise normal cardiac scans. This supports the idea that persistent fatigue and post-exertional crashes may be as much about capillary health as clotting.
Endothelial Senescence: When Blood Vessels Age Too Fast
Even where capillaries survive, their lining may not work properly. That lining called the endothelium is central to vascular health. It helps blood vessels dilate, stay non-sticky, and communicate with the immune system.
After COVID, many patients show signs of endothelial senescence cellular ageing triggered by stress and inflammation. Senescent cells release inflammatory signals, become stiff and leaky, and stop supporting circulation efficiently.
This process may:
- Contribute to blood brain barrier disruption
- Impair exercise recovery
- Fuel autonomic dysfunction (like POTS)
- Maintain an environment ripe for clotting, inflammation, and poor healing
And crucially, this damage may persist long after the virus has cleared.
Why This Matters for Recovery
Many Long COVID patients have:
- Tried clot targeted therapies but remain symptomatic
- Normal scans and tests, but still can’t function
- Symptoms that shift and evolve, from fatigue to brain fog to dizziness to muscle pain
If the problem is not just blocked blood flow but damaged vessels and lost capillaries, we need broader answers.
We may need therapies that:
- Support vascular regeneration
- Reverse endothelial senescence
- Improve oxygen extraction at the tissue level
- Rebuild the microvascular network
- Reduce inflammation without suppressing immune recovery
🔍 What the 2025 Research Says
New studies suggest:
- Capillary loss (rarefaction) in Long COVID may be similar to changes seen in ME/CFS, diabetes, and ageing
- Endothelial dysfunction markers (like VCAM-1, VEGF, and nitric oxide imbalance) persist in patients well beyond the acute phase
- Microclots are part of this, but they don’t account for the entire picture especially in patients who’ve improved clotting markers but not symptoms
It’s increasingly clear: Long COVID is a vascular disease.
Where Do We Go From Here?
If you’ve improved a little on microclot therapies but hit a wall, you’re not alone — and you’re not imagining it.
It may be time to ask:
- How can we restore vascular integrity, not just remove clots?
- Can therapies for vascular ageing or mitochondrial dysfunction help?
- Should we screen for endothelial dysfunction in Long COVID clinics?
- What about supporting angiogenesis (new blood vessel growth)?
These are the questions 2025 researchers are beginning to ask and we’re hopeful that real-world answers are on the way.
Final Thoughts
Long COVID is not one disease. It’s a syndrome with multiple overlapping layers clotting, vascular injury, immune activation, and metabolic exhaustion.
To truly help people recover, we need to zoom out and start treating the vessels themselves.
Disclaimer
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before starting or changing any treatment related to Long COVID or other health conditions. Research is evolving, and individual responses may vary.
Long Covid Journey 