Genetic analysis using the Oak Ridge National Lab supercomputer called the Summit has revealed an interesting new hypothesis that helps explain the disease progression of COVID-19. A September 1, 2020, Medium article¹ by Thomas Smith reviewed the findings of what is now referred to as the bradykinin hypothesis. 

As reported by Smith, the computer crunched data on more than 40,000 genes obtained from 17,000 genetic samples.

“Summit is the second-fastest computer in the world, but the process — which involved analyzing 2.5 billion genetic combinations — still took more than a week. When Summit was done, researchers analyzed the results. It was, in the words of Dr. Daniel Jacobson, lead researcher and chief scientist for computational systems biology at Oak Ridge, a ‘eureka moment.’” 

The Bradykinin Hypothesis

Bradykinin is a chemical that helps regulate your blood pressure and is controlled by your renin-angiotensin system (RAS). As explained in the Academic Press’ book on vitamin D (which has a significant impact on the RAS):²

“The renin-angiotensin system (RAS) is a central regulator of renal and cardiovascular functions. Over-activation of the RAS leads to renal and cardiovascular disorders, such as hypertension and chronic kidney disease, the major risk factors for stroke, myocardial infarction, congestive heart failure, progressive atherosclerosis, and renal failure.”

The bradykinin hypothesis provides a model that helps explain some of the more unusual symptoms of COVID-19, including its bizarre effects on the cardiovascular system. It also strengthens the hypothesis that vitamin D plays a really important role in the disease.

The findings³ were published in the journal eLife July 7, 2020. Based on this new hypothesis, the researchers also suggest more than 10 potential treatments, most of which are readily available drugs already approved by the U.S. Food and Drug Administration. I’ll review those later on.

As detailed in previous articles, your ACE2 receptors are the primary gateways of the virus, as the virus’ spike protein binds to the ACE2 receptor. As explained by Smith:⁴

“… COVID-19 infection generally begins when the virus enters the body through ACE2 receptors in the nose … The virus then proceeds through the body, entering cells in other places where ACE2 is also present: the intestines, kidneys, and heart. This likely accounts for at least some of the disease’s cardiac and GI symptoms.

But once Covid-19 has established itself in the body, things start to get really interesting … The data Summit analyzed shows that COVID-19 isn’t content to simply infect cells that already express lots of ACE2 receptors. Instead, it actively hijacks the body’s own systems, tricking it into upregulating ACE2 receptors in places where they’re usually expressed at low or medium levels, including the lungs.

In this sense, COVID-19 is like a burglar who slips in your unlocked second-floor window and starts to ransack your house. Once inside, though, they don’t just take your stuff — they also throw open all your doors and windows so their accomplices can rush in and help pillage more efficiently.”

Bradykinin Storm Likely Responsible for Lethal Effects

In addition to upregulating ACE2 receptors throughout your body, the SARS-CoV-2 virus also downregulates your body’s ability to degrade or break down bradykinin. 

The end result is a bradykinin storm, and according to the researchers, this appears to be an important factor in many of COVID-19’s lethal effects, even more so than the cytokine storms associated with the disease. As bradykinin accumulates, the more serious COVID-19 symptoms appear. 

Mounting clinical data suggest COVID-19 is actually primarily a vascular disease rather than a respiratory one, and runaway bradykinin buildup can help explain this.