Is a bradykinin storm the cause of COVID-19 lung problems? RAZOR
How does COVID-19 take over a patient's system? RAZOR has been exploring a new theory about that and finds out what causes fluid build-up in patients' lungs.
The premise is that an excess of bradykinin, an inflammatory molecule made up of a short chain of amino acids, may be the cause of fluid build-up in the lungs of COVID-19 patients.
Clinical trials of inhibitors are now testing this hypothesis and there are several potential treatments that have already been approved by the U.S. Food and Drug Administration.
Daniel Jacobson, the lead researcher for computational systems biology at Oak Ridge National Laboratory in Tennessee, U.S., has called it "a eureka moment".
Bradykinin helps regulate blood pressure and blood vessel permeability. It is part of the kallikrein-kinin hormone system and intersects with the renin angiotensin system, which controls many aspects of the circulatory system, including the body's levels of bradykinin.
It is essentially a system with an accelerator and a brake, in which an infection presses down the accelerator pedal while the brake tries to keep the acceleration from getting out of control.
When the virus hits the renin-angiotensin hormone system, the body overproduces and stops breaking down bradykinin.
"We're calling this a bradykinin storm, where it's out of control and that leads you to the spiral of outcomes," says Jacobson.
"Excess bradykinin will lead to gaps in your blood vessels. It permeabilizes your blood vessels so fluid will actually start to leak out, your blood pressure will go down, you start to lose fluid. It also leads to inflammatory responses," explains Jacobson.
The world is still waiting for a vaccine, but with this hypothesis, if the research bears out, there are multiple therapeutics that already exist that can put the brakes back on this bradykinin storm.
"I think right now we're looking at about a dozen different drugs that can be applied here," says Jacobson. "We want to be very careful. We're always worried about the law of unintended consequences: there can be side-effects of drugs. We want to make sure you don't do something to accidentally make something worse."