Hydrogel in alveoli - covid pneumonia mechanism and bradykinin hypothesis
Why high dose Vit D and corticosteroids seem to help
Early on in this coronavirus ‘pandemic’ the focus and fear targeted rapid onset pneumonia, and hence the panicked push for ventilators. China docs reported using CT scans to quickly diagnose patients, bypassing the PCR tests which were in limited supply at the time. One of the hypotheses that took hold and gained some traction, was the bradykinin hypothesis for mechanism of action. Given that most vaccines generate the spike protein which binds to ACE2, vaccine adverse reactions may, too, involve the RAS [renin-angiotensin-system] and hence, bradykinin [BK}.
The angiotension converting enzyme [ACE] also works to activate bradykinin, not just angiotensinogen. And where does the BK come from? Well, SARS-CoV-2 infects the mast cells, especially in the lungs. And they release lots of factors, BK being one of them. [fyi-Mast cell stabilizers include Vitamin D3, ketotifen, cromoglycate, quercetin, luteolin, Vitamin C.]
In the BK induced cytokine storm, the lung upregulates hyaluronan [HA] synthases, downregulates the hyaluronidases. When combined with the vascular hyperpermeability, the alveoli fills with HA hydrogel - a ‘jello-like’ substance that does not exchange gases.
So, we just have to get rid of all that mucus, right? Not so easy to do. The Hyaluronic acid [HA] breakdown half life is very long, in the range of months (designed to last, because it fills/lubes the joint spaces). What are the known regulators?
HA increases via synthesis when triiodothyronine [T3] tissue level is low, and synthesis is reduced when T3 is high. But there is no effect on degradation. Once HA is present, have to wait for it to slowly breakdown. Corticosteroids effect HA similarly to thyroid hormones, by regulating the rate of synthesis. Gonadal steroids do too, but in the opposite direction. That is, testosterone and estradiol directly enhance the synthesis of that ‘joint juice’ HA.
Butyrate [butyric acid] also regulates HA - stimulating accumulation at low dose but inhibiting it at high doses. And it is often used as a carrier vehicle for Vitamin D infusions — likely also for other steroids, including corticosteroids. So be aware of this when you see high dose infusions of lipophilic drugs, such as steroids. Effects may be due to nonspecific carrier effects.
REFERENCES
Mast cell stabilisers and covid-19 https://www.bmj.com/content/370/bmj.m2722/rr-3
https://bgr.com/2020/09/01/coronavirus-drugs-that-work-bradykinin-storms-icatibant/
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COVID or COVID vaccination can cause dermal fillers to swell up (2022, October 13) https://medicalxpress.com/news/2022-10-covid-vaccination-dermal- fillers.html
hyaluronidase inhibitors... does include sodium cromolyn. [https://pubmed.ncbi.nlm.nih.gov/14602119/]
So, cromolyn could slow down the break down of the hydrogel.
"Mast Cells and Their Products
It has been demonstrated that mast cells constitute an innate immune mechanism to
counteract the toxicity of venoms produced by various animals, including snakes.
This is based on the action of mast cell proteinases, especially tryptase, which selectively
cleaves venom toxins. In addition, heparin, another mast cell-derived substance
was shown to inhibit myotoxic and cytotoxic toxins in viperid venoms"
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8309910/pdf/toxins-13-00451.pdf]