The Bradykinin Hypothesis of ARDS
The Bradykinin Hypothesis is one idea to explain why Covid-19 becomes serious in some people. It is based in part on a study that involved data mining the activity of 40,000 genes in the body, and it provided some new possibilities on what changes in people who fare poorly from Covid-19. In a nutshell, disruption to the bradykinin system can make blood vessels leaky. This is consistent with simple observations that the disease is involves vascular abnormalities - clotting in the lungs and extremities.
The Bradykinin hypothesis does not directly negate the most widely cited alternative idea - the cytokine storm. In fact, there are lots of inflammatory cytokines present in people who are hospitalized with covid-19. The bradykinin hypothesis merely states that bradykinin system is deranged much more in Covid-19 than in other diseases that involve lots of cytokines - and the bradykinin may be a key thing that causes disease and death. This is something that can be tested over time, and it won't be long before hospitals will trial medicines that inhibit bradykinin. It's complicated stuff. Bradykinin does not act alone, it forms a system with other things like rennin and angiotensin, kallikrein and kinin, it interacts with many other signalling molecules like the eicosanoids. Complicated stuff, but the role of bradykinin is emerging as more important that we previously thought.
CB2 receptors and bradykinin? Yes, there is interaction. There is basic research that shows that the experimental drug AM1241 (which is a CB2 agonist) lowers bradykinin activity on the nerves when administered on its own. But when given along with another drug that blocks the CB2 receptors (AM630), no such effect was seen. This provides good evidence that the CB2 receptors can play a beneficial role - sometimes. As to whether this effect will help with a SARS2 infection and Covid-19, we do not yet know. 1
General Links on the Bradykinin Hypothesis
- A Supercomputer Analyzed Covid-19 — and an Interesting New Theory Has Emerged
- Snake venom-derived bradykinin-potentiating peptides: A promising therapy for COVID-19?
- A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm.
- A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications.
- Kallikrein-kinin blockade in patients with COVID-19 to prevent acute respiratory distress syndrome.
- [ https://pubmed.ncbi.nlm.nih.gov/32405877/ A Review: Does Complement or the Contact System Have a Role in Protection or Pathogenesis of COVID-19?]