Supercomputer’s Findings Suggest Why Patients Worsen, Get Range Of Symptoms

The bizarre cascade of effects of the coronavirus may be due to the excessive production of a chemical that regulates blood pressure — throwing the body’s respiratory, gastrointestinal, and neurological pathways off-balance, a new study has found.

Researchers at the Oak Ridge National Laboratory in Tennessee, using its supercomputers — one of which is the second-fastest in the world — analyzed lung fluid samples from nine coronavirus patients with severe cases in Wuhan, China, Business Insider reported.

The computers detected big differences in way the patients expressed certain genes relative to the way healthy people do. Based on those abnormalities, the researchers came up with a new theory: Patients with severe COVID-19 may experience what’s known as a “bradykinin storm.”

The blood pressure regulating chemical produced extreme excess and throws off major body systems, they found — a theory that aligns with researchers’ growing view of the coronavirus as a vascular disease instead of a respiratory one, BI reported.

We were really scratching our heads for a while, how does this disease have this darn broad set of symptoms across lots of different organ systems?” Dr. Daniel Jacobson, the lead researcher behind the supercomputer study, told BI.

‘”As we looked at the effects of bradykinin, our model was that this virus can affect several different types of tissues, several different organs.”

Scientists already know that the coronavirus binds to cell receptors called ACE2. That’s how the virus sneaks into the body’s upper respiratory tract, then infects organs like the lungs, heart, kidneys, or intestines.

But the supercomputers found coronavirus patients had a 200-fold increase in the expression of ACE2 relative to a healthy person, and an eight-fold decrease in the expression of ACE, a protein that normally works with ACE2 to keep blood pressure in check.

“This system that is normally very carefully balanced — COVID-19 really throws it out of whack,” Jacobson told the news outlet.

The researchers believes the imbalance leads to the over-production of bradykinin, which swoops in to keep blood pressure from getting too high. In severe cases, the cycle seems to go into overdrive: The body can’t stop producing bradykinin. This is what researchers call a “bradykinin storm.” BI reported.

“Everywhere we go in the body and look at the symptoms being reported, they map pretty well to exactly what you’d expect to see from bradykinin,” Jacobson told BI.

In May, Michigan researchers also hypothesized that a bradykinin response could lead to life-threatening respiratory complications in some COVID‐19 patients, finding the bradykinin response was to blame for leaky blood vessels observed in those patients’ lungs, BI reported.

The researchers behind that work suggested that a drug called icatibant, which blocks the body’s signal to produce bradykinin, could help treat infected patients. A small follow-up study showed that four of nine patients who got the drug no longer needed oxygen support after 10 to 35 hours. 

But Jacobson’s study found evidence vitamin D might hinder a bradykinin storm from developing in the first place. His study also supports the idea that corticosteroids can improve survival rates for COVID-19 patients. 

“To be honest, I’m worried that this proposal is almost too neat and form-fitting,” Derek Lowe, a medicinal chemist, wrote in Science Magazine. “Rarely do you get something that falls together this well.”

Still, he added, the findings are “pretty plausible.”

According to BI, Jacobson’s team thinks once that bradykinin storm takes off, it could continue until the body figures out how to reset it. It’s  unclear whether any available treatments would make a difference for long-haul patients.

“That’s part of the joy of science,” Jacobson told BI. “For every answer you have, it raises 10 more questions.”Related Stories:

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