The Hindu Explains | Is COVID-19 setting off a bradykinin storm in the body?

Why are some patients showing a rapid accumulation of fluid in the lungs? What have scientists found out?

The story so far: Scientists are still trying to understand the causes for the rapid deterioration in some patients with COVID-19. While the cytokine storm is able to explain certain aspects of what goes wrong, doctors treating patients are often foxed by the severity with which the SARS-CoV-2 virus seems to affect some people. A supercomputer’s recent analysis of data on the contents collected earlier from the lungs of patients with the COVID-19 infection has showed that a phenomenon called a ‘bradykinin storm’ might explain how the virus works in the body, including some of the more puzzling extreme events.

How has this explanation emerged?

This plausible explanation has emerged from the data analytics work that a team of scientists led by Dan Jacobson at the Oak Ridge National Laboratory (ORLN) in the U.S. have been doing employing the super computer Summit. In a paper published in July in eLife, a peer reviewed journal, Michael R. Garvin et al advance the bradykinin hypothesis as a means of explaining some of the more deadly effects the virus has on the human body.

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What is the bradykinin hypothesis?

Bradykinin is a compound that is related to pain sensation and lowering blood pressure in the human body. According to the researchers, “SARS-CoV-2 uses a human enzyme called ACE2 like a ‘Trojan Horse’ to sneak into the cells of its host. ACE2 lowers blood pressure in the human body and works against another enzyme known as ACE (which has the opposite effect).” The analyses further found that the virus caused the levels of ACE to fall in the lungs, and consequently pushed up the levels of ACE2. As a chain reaction, this increases the levels of the molecule bradykinin in the cells, causing a bradykinin storm. Bradykinin causes the blood vessels to expand and become leaky, leading to swelling of the surrounding tissue.

In addition, the levels of a substance called hyaluronic acid, which can absorb more than 1,000 times its own weight in water to form a hydrogel, increased. “In effect, the bradykinin storm-induced leakage of fluid into the lungs combined with the excess hyaluronic acid would likely result in a Jello-like substance that is preventing oxygen uptake and carbon dioxide in the lungs of severely affected COVID-19 patients,” the researchers explain. This rapid accumulation of fluid in the lungs of patients sometimes makes even the most sophisticated intensive care, including ventilators, futile. Meanwhile, The Scientist reported that Frank van de Veerdonk, an infectious disease specialist at the Radboud University Medical Centre in the Netherlands, and his group independently came up with a hypothesis that a dysregulated bradykinin system was leading to leaky blood vessels in the lungs and perhaps causing excess fluid to build up.

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Is more confirmation needed?

The Scientist brought in Josef Penninger, director of the Life Sciences Institute at the University of British Columbia in Vancouver, to weigh in on this question. “It does make a lot of sense,” he told the magazine. He went on to add that further confirmation was needed, in terms of actually measuring the proteins. The magazine also reported the efforts of van de Veerdonk to set up mass spectrometry to measure kinins in the plasma.

What follows confirmation of this hypothesis?

Jacobson and other scientists have advocated targeting the bradykinin pathway to evolve more therapeutic interventions to offset the severe effects of COVID-19. Repurposing of available drugs, subject to the outcome of clinical trials, has also been suggested.

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