RAS and Bradykinin: Where COVID-19 and ME/CFS Meet?

ScottTriGuy said:
Bradykinin Hypothesis for Covid

Any relevance to ME? I haven't looked for Bradykinin and ME research.


https://elemental.medium.com/a-supe...teresting-new-theory-has-emerged-31cb8eba9d63
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I had just read the same article, and was wondering that as well.
Medium said:
According to the researchers, bradykinin storms could create arrhythmias and low blood pressure, which are often seen in Covid-19 patients.
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Medium said:
If bradykinin storms cause the blood-brain barrier to break down, this could allow harmful cells and compounds into the brain, leading to inflammation, potential brain damage, and many of the neurological symptoms Covid-19 patients experience. Jacobson told me, “It is a reasonable hypothesis that many of the neurological symptoms in Covid-19 could be due to an excess of bradykinin.
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I know very little about biology but...
Bradykinin is a potent endothelium-dependent vasodilator and mild diuretic, which may cause a lowering of the blood pressure. It also causes contraction of non-vascular smooth muscle in the bronchus and gut, increases vascular permeability and is also involved in the mechanism of pain
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Yes, quite. It's one thing to speak of multi-system diseases but some systems are kind of their own while affecting every other system.

Anyway no point in speculating but it's usually helpful when a hypothesis actually, you know, fits with the evidence.
 
ScottTriGuy said:
Bradykinin Hypothesis for Covid

Any relevance to ME? I haven't looked for Bradykinin and ME research.


https://elemental.medium.com/a-supe...teresting-new-theory-has-emerged-31cb8eba9d63
Click to expand...

No direct relevance to ME in my opinion.

The hypothesis isn't really that "new", I remember it being proposed on Twitter back in March and hypotheses published in April and May:
https://www.bmj.com/content/368/bmj.m810/rr-35 (March comment)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267506/
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32338605/


I think it is misleading to talk about "cytokine storms" and "bradykinin storms". The word "storm" in particular is misleading - "storm" implies off the chart levels due to aberrant feedback. Bradykinin certainly plays a role in the pathology, but there is a lack of evidence (and it is unlikely) for off-the chart levels and it's also possible that it is a beneficial response to ACE2 antagonism by viral related activity.

A large increase in bradykinin would lead to symptoms of angioedema in the absence of Urticaria. There have been a few case reports of this occuring in COVID19 patients, but as far as I know, none of them reported the patient dying... One case study of hereditary angioedema did not find an exacerbation during a "mild" course of COVID19.

Bradykinin may actually be beneficial in helping clear the immune complexes. Bradykinin helps increase blood flow through vasodilation, particularly microvascular flow (which is less effected by autonomic control).
Thus I could construct a similarly evidenced (but speculative) hypothesis explaining why bradykinin could be helpful. This is the danger of confirmation bias...

The mention of hyaluronic acid as some kind of danger can be misleading too, hyaluronic acid is a key component of the extracellular matrix and plays a role in wound healing / tissue regeneration.
 
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