Thread by @ZdenekVrozina

COVID-19 doesn’t just cause inflammation.
It switches off the genes that repair blood vessels - and switches on those that drive inflammation and destruction.
And what’s worse - this state lasts for at least six months, long after the infection is gone🧵

https://twitter.com/harryspoelstra/status/1976283806328918396

Researchers studied endothelial progenitor cells - the special cells that normally repair blood vessels after injury.
In people recovering from severe COVID (before vaccines even existed), they found these repair cells were genetically reprogrammed.

The healing genes were switched off.
NOS3 - produces nitric oxide to relax vessels
KLF2 - master regulator of endothelial health
ANGPT1, TGFB1, SMAD6 - maintain vessel stability and repair
The body’s vascular repair system went silent.

At the same time, genes linked to inflammation and cell death were switched on.
CASP1 - pyroptosis, an inflammatory form of cell death
CXCL5, IL12A, TLR2 - recruit immune cells
SOD2, TIMP3, VEGFA - oxidative stress and chaotic vessel growth
The system that should heal - stays angry.

Even after 6 months, this abnormal gene pattern remained.
No recovery. No reset.
The endothelial system stayed stuck in post-trauma mode.
Scientists call it persistent endothelial dysfunction.

Biological consequences.
This long-term shutdown of the repair program can
cause chronic fatigue and poor microcirculation,
increase the risk of microclots and vascular aging,
and potentially underlie Long COVID itself.

These patients were infected with early variants (Wuhan/Alpha) - the ones with a strong affinity for blood vessel cells.
But the mechanism - the switching off of KLF2–eNOS signaling - could still happen with newer variants, just more quietly.

“The sustained downregulation of KLF2–eNOS–TGFβ signaling suggests a long-lasting inability of endothelial progenitor cells to recover their reparative function.”
= the blood vessels forgot how to heal.

Forgotten repair - that’s what this study reveals.
Even months later, the body’s vessel repair cells remain inflamed and dysfunctional.

Poyatos et al., iScience 2025. sciencedirect.com/science/articl…

This pattern isn’t unique to COVID.
We’ve seen similar endothelial reprogramming in other chronic conditions.
HIV suppresses KLF2 and eNOS, driving vascular inflammation.
CMV activates TLR2/IL-1β pathways, impairing vessel repair.
Aging downregulates KLF2, ANGPT1, NOS3 - activates CASP1 and SOD2.

COVID seems to combine all three -
a viral infection that leaves the endothelium older, inflamed, and unable to heal.