Is bradykinin responsible for the covid-19 cough?

Article written by Christine Clark

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.

References

1. 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

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