Hadn't heard about this before. Really interesting stuff. Makes a lot of sense.

RandyAg98 said:

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I really respect your insight and opinion, and would really like your thoughts on the new "bradykinin storm hypothesis" based on your front line experiences. Apologies if I missed them elsewhere.

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Thank you. It is indeed interesting. There may be something to it. But, there are inconsistencies in the theory that do contradict some of the pathophysiology and histopathology of covid we already know. Bradykinin has been known to be a potent vasodilator and cause capillary leak at high plasma levels.



ACE-I have historically inhibited bradykinin binding to B2 receptors, internalizing them, thus leading to high levels serum and extracellular bradykinin. Interestingly, this is thought to cause irritation of J receptors of the lung and the cough side effect seen in up to 1/3 of pts on ACE-Is. ACE-2 receptors block binding of the bradykinin degradation product to the B1 receptor. Covid binds to ACE-2 receptors, also internalizing them, leading to higher serum and extracellular bradykinin breakdown products.



Angioedema - a condition of marked inflammatory swelling of the face, lips and tongue, potentially fatal, is thought to occur via excessive bradykinin induced vascular leak and edema. It can occur as a side effect of ACE-Is and congenital C1 esterase inhibitor deficiency syndrome - as is shown on the above graphic.

The authors are theorizing that capillary leak and pulmonary edema is occurring from covid induced excess
bradykinin degradation products. But, I have not seen nor heard of angioedema of the upper airway with covid. And autopsy series have not shown capillary leak pathology or hyaline membrane disease in the lung, as seen in ARDS/DAD. This would be expected in an "angioedema of the lung" phenomenon. Rather - more thrombotic pathology has been described. Which is not consistent with bradykinin physiology to my knowledge.

Anyway - complex. Studies need to be done analyzing bradykinin and degradation products in covid, as well as type 2 alveolar cell B1 and B2 cell receptor quantities. Good news is there are multiple drugs affecting bradykinin metabolism. If this is true it could lead to new therapies.