Is a 'Bradykinin Storm' Brewing in Your Patient?

 

The causes of some of the life-challenging aspects of a Covid-19 infection in some patients appear to be gradually becoming clearer (https://www.the-scientist.com/news-opinion/is-a-bradykinin-storm-brewing-in-covid-19--67876). The main features of patients with a 'bad' Covid-19 infection are fluid in the lungs and signs of inflammation (hence treatments with dexamethasone and hydrocortisone). It has been established that the receptor for SARS CoV-2 (the virus that causes Covid-19) is a protein called Angiotensin Converting Enzyme-2 (ACE2) which is found in the tissues of the nose as well as other areas of the body. These receptors, in the nose, presumably pick up the virus in the aerosols generated by infected people. ACE2 is one of the regulators of the kinin-kallikrein hormonal system that plays roles in inflammation, blood pressure control, coagulation (clotting) and pain. Knocking out ACE2 seems to dysregulate (it stops the control of the level) of a factor called bradykinin, producing a 'bradykinin storm'. Bradykinin reduces blood pressure and one of the ways it does this by being a potent dilator (causing an increase in diameter, with a corresponding thinning of the walls) of blood vessels (especially the tiny capillaries). This increases vascular permeability (blood vessels become more leaky) and oedema (a build up of plasma fluid) occurs in organs, including the lungs. Bradykinin also causes contraction of smooth muscle in the bronchi (the tubes going to the lungs) and the gut. There have been small, preliminary trials with drugs (such as icatibant), which block the kinin system. They appear to improve oxygenation in respiratory challenged patients but better (bigger and double-blind) trials are needed. So, many of the serious effects of a Covid-19 infection appear to be a consequence of the induction of a 'bradykinin storm'. Why such 'storms' appear to be more common in certain categories of the population (the older and those with additional risk factors) is, as yet, unanswered.