Very interesting. But I'm a cancer guy, and know almost nothing about bradykinin and what regulates the renin-angiotensin system (RAS) pathway. So, I'll wait to hear from TLS Guy. As an ICU guy, he'll have plenty to say about blood pressure regulation systems and SARS-CoV-2.
It certainly suggests a new set of drug targets to look into. Look for treatments that increase the turnover of bradykinin, or decrease it's signalling level.
Vitamin D takes days or weeks to act. I doubt if it can do anything fast enough to matter for a patient in acute respiratory or vascular distress.
I do wonder about the comment that dismisses the cytokine storm hypothesis. Treatments that cool down the cytokine storm, cortico-steroids (dexamethasone), and antibodies against IL-6 were reported to be clinically effective. It may very well be that both storms are going on at the same time.
I think that issue was more eye catching than anything new. In the inflammatory cascade it is bradykinin that triggers the cytokine storm, so I don't think this is news.
However Coavid-19 is primarily a vascular infection. It damages the blood vessels, not only causing blood clotting, but also rupture of blood vessels and bleeding. It enters the body though angiotensin II receptors and damages them. This is what makes Covid-19 such a dangerous infection and nothing like flu. We have never encountered anything like this before. Now once the bradykinin/angiotensin cascade is activated, blood pressure drops and has to be supported with infusion of nor-epinephrine or vasopressin. The damage done to the angiotensin receptors, makes blood pressure control a hugely difficult task in these patients.
Blood pressure control is very complex with hormonal, and neurological feedback loops that are interrelated. The involves baroreceptors in blood vessels, heart and kidney. The hormonal organs are principally the kidneys and pituitary. The autonomic nervous system is also involved including both sympathetic and parasympathetic systems.
Here is a simplified diagram of it all, but it actually much more complicated than this diagram indicates.
The real take home is that everyone will remain at risk from a potentially devastating illness until it is brought under control by vaccination.
So I think a reasonable time line is starting to develop. There is a remote possibility of having a small supply of vaccine available at the end of next month. There is a reasonable chance of having enough vaccine for front line personnel by years end, may be 20 million doses. I think we are nine months away from having enough vaccine to get herd immunity up to where life can return to some sort of reasonable normality. I expect the next four months in particular to be very difficult and tragic.
We are seeing what I feared as universities in particular, and schools open. The UK is seeing the same issues we are with the return of university students, and the universities are not due to open in the UK for another two weeks. Personally I think universities should only be open for distance learning for this academic year.
So my sense that we are now about at the half way point of this crisis. I'm timing it from January when there was evidence that the world was about to face a really serious crisis. It has turned out that way. It will end, and my advice is to lay low and do everything possible to avoid getting and spreading this very dangerous infection.
