Is bradykinin responsible for the covid-19 cough?
The similarities between the ACE-inhibitor cough and the cough of covid-19 prompted Dr Colin Brown, a retired GP and researcher, to investigate further.
The ACEI cough is due to accumulation of bradykinin and its active metabolite, des-arg-bradykinin (DABK), and this occurs because ACE normally breaks down bradykinin and DABK to inactive compounds.1 Bradykinin is an inflammatory peptide that causes increases in vascular dilation, vascular permeability and hypotension. In the lungs it causes pain and cough.
In covid-19, it is now well known that the virus uses ACE2 for cell entry so disrupts ACE2 systems, but it was only recently found that it also disrupts the renin-angiotensin system (RAS), effectively functioning like an ACE inhibitor, and resulting in an increase in bradykinin levels. This has been described as a ‘bradykinin storm’.2
“Our proposition is that the covid cough is directly caused by bradykinin as well as by damage in the lung”, says Dr Brown.
- Yılmaz İ. Angiotensin-Converting Enzyme Inhibitors Induce Cough. Turk Thorac J. 2019;20:36-42. doi:10.5152/TurkThoracJ.2018.18014
- Garvin MR, Alvarez C, Miller JI, et al. A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. Elife. 2020;9:e59177. Published 2020 Jul 7. doi:10.7554/eLife.59177