The Bradykinin Hypothesis for COVID

September 07, 2020

The Bradykinin Hypothesis for COVID

Bet you haven't heard of "bradykinin"! Most haven't. It is part of the balancing system of your blood pressure. When you take an ACE Inhibitor for your blood pressure, you are lowering the activity of ACE, but raising bradykinin. So the bradykinin system lowers your blood pressure and makes blood vessels ooze out fluid and get leaky. Then it intersects with your immune response, and everything else.

The data for this important study comes from analyzing the messenger RNA activated in 9 COVID patients in China. The patients were having the virus sampled so they could sequence its genes. The rest of the lung fluid was not used. This study took that lung fluid and analyzed the mRNA (messenger RNA) in the human cells to see just what genes were turned on in those humans. mRNA tells you that. It is produced only when genes are activated. You can see what the cell is thinking is happening and how it should respond. Nifty, huh?! Now, run all that data through the second fasting supercomputer in the world at Oak Ridge for a week and this hypothesis emerges. Compare these 9 sick folks with 40 normal controls and you get this study.


And the changes in gene activation weren't subtle. The ACE2 gene was up 199 fold, angiotensin - 34 fold, and the enzyme that activates it, REN, up380 fold. Other pertinent enzymes like the angiotensin receptor 1, (ACGR1), up 430 fold. This is a remarkable and very dramatic change to your balance of your angiotensin/bradykinin balancing act.

And it helps explain many of the weird symptoms of COVID. Low blood pressure, loss of smell and taste, puffy toes, Lungs fill up with jello-like fluid, explained by the bradykinin activation of hyaluronic acid. The shifting balance between angiotensin and bradykinin also explains the weird blood clotting and emboli that COVID has demonstrated. Lungs end up weighing over 4 times normal lungs.  

The net effect of all this activation of bradykinin is that the virus gets in the cells and takes over the house, sort of like a burglar that not only breaks in but opens all the doors and windows and lets in everyone else. Hence the storm.

By focusing on the genes that are activated, you can parse our the real cause of the ongoing damage in COVID. And if you chase that down, quite a few drugs emerge that have specific impact on the bradykinin system. This gives hope for future treatments and will require good, randomized trials to see if anything emerges.

But for now, one simple strategy you can do comes forward. Vitamin D. It has already been shown to have a dramatic effect in COVID patients, which would explain much of the tilt of severe COVID disease in folks with skin pigment, which inhibits Vitamin D production and elderly whose skin doesn't make much.

References: eLife Sciences, Wikipedia, MedRxIV, Elemental, Elemental - Vitamin D, Science Daily,

WWW: What will work for me. I'm taking Vitamin D every day. Daily use has been shown to be better than monthly by some increment. So, it's worth the extra effort. And I'm really trying not to be too lax about exposure. I forgot to take a mask on a bike ride and we got off in a park with other folks around. There was lots of wind, so the risk was low. But small micro errors will add up in time. We are only 6 months away from the credible chance for a vaccine. Hang in there.

Pop Quiz:

1. What is the bradykinin system? Answer: part of your blood pressure control system that is intertwined with your immune response system.

2. How did this study detect that notion? Answer: they analyzed the activated genes by measuring the messenger RNA in COVID lung fluid compared to controls.

3. What difference does all this make? Answer: It's September and the sun is no longer high enough to make much Vitamin D. If you are older, hence less able to make D (80% reduction by age 70), or have skin pigment (85% reduction if skin type 6 - Ivory Coast Black) please, please take 5000 iu a day. If you are just starting from scratch, take 20,000 a day for a month to get loaded up.

4. What else can I do to stay ahead of this pandemic? Answer: Same story. Avoid indoor large groups that have prolonged exposure.

5. Where else is the messenger RNA measurement being used to beneficial effect? Answer: You can measure activated DNA via mRNA molecules in the exosome fraction of your blood. It is being used clinically in patients with Chronic Inflammatory Response Syndrome by Ritchie Shoemaker. This might be the future all all medicine, the assessment of how your body turns on its genes and what that portends for clinical decisions.