Review Inflammation-, immunothrombosis,- & autoimmune-feedback loops may lead to persistent neutrophil self-stimulation in long COVID, 2024, Thierry & Salmon

Inflammation-, immunothrombosis,- and autoimmune-feedback loops may lead to persistent neutrophil self-stimulation in long COVID
Alain R. Thierry; Dominique Salmon

Understanding the pathophysiology of long COVID is one of the most intriguing challenges confronting contemporary medicine. Despite observations recently made in the relevant molecular, cellular, and physiological domains, it is still difficult to say whether the post‐acute sequelae of COVID‐19 directly correspond to the consequences of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection.

This work hypothesizes that neutrophils and neutrophil extracellular traps (NETs) production are at the interconnection of three positive feedback loops which are initiated in the acute phase of SARS‐CoV‐2 infection, and which involve inflammation, immunothrombosis, and autoimmunity. This phenomenon could be favored by the fact that SARS‐CoV‐2 may directly bind and penetrate neutrophils. The ensuing strong neutrophil stimulation leads to a progressive amplification of an exacerbated and uncontrolled NETs production, potentially persisting for months beyond the acute phase of infection.

This continuous self‐stimulation of neutrophils leads, in turn, to systemic inflammation, micro‐thromboses, and the production of autoantibodies, whose significant consequences include the persistence of endothelial and multiorgan damage, and vascular complications.

Link | PDF (Journal of Medical Virology) [Open Access]

 

NEGATIVE TAKE

This is a hypothesis paper. I made a comment in another thread recently about how easy it is to make up credible theories of mecfs. They're easy to generate. Useful, but cheap to make. What we really need is to match the rate of hypothesis generation with high-speed falsification: data. We need more constraints on hypotheses, more hurdles to clear and more hoops they need to jump through.

POSITIVE TAKE

When I look at a theory like this, I think about Trikafta, the recent breakthrough drug that essentially cures 90% of cystic fibrosis cases.

It doesn't hit the disease at its root, the genetic cause. Instead it uses a combination of three treatments that each addresses one of the mechanisms of the disease.

It seems likely that in mecfs and long covid we have diverse immune system problems that are part of the problem but not the whole problem. A combo treatment that improves several of these measurable problems might create noticeable symptom relief, moving people from severe to moderate. Perhaps it may even generate sfficient relief that the body can then heal the underlying issue, at least for some people.

 

Trendy garbage I am afraid.

 

One thing I think we can be sure of is that there will be no NETs anywhere near brain endothelium in Long Covid. NETs are clumps of dead neutrophils outside the circulation in the tissue. If that was going on in the brain you would be on ITU with a tube in.