‘Bradykinin hypothesis’ may explain how COVID-19 attacks the human body

TORONTO — Scientists may be getting closer to answering a key question about the novel coronavirus – and all it took was tying up the world’s second-most-powerful computer for seven days.

One of the many things yet to be understood about the virus is exactly how it is able to attack the human body in so many different ways and cause so many different symptoms, from persistent heart disease to the inability to smell and taste to the skin lesions that have been dubbed ‘COVID toes’.

Early on in the pandemic, some doctors suggested the variety of symptoms could be explained as the work of cytokine storms – processes in which the immune system overreacts to an infection.

Cytokines are one of three types of molecule that the body produces in response to a virus or another invader. Normally, humans stop producing cytokines once the threat has been defeated. In a cytokine storm, however, the immune system keeps producing them – and they end up attacking the organs they were meant to protect.

More recent research suggests that one of the other defender molecules may be the culprit. It’s been dubbed the “bradykinin hypothesis,” and it’s gained steam ever since it was first theorized in the journal eLife in July.

Using the Summit supercomputer at the Oak Ridge National Laboratory in Tennessee – considered to be the second-most-powerful computer in the world – a team of researchers led by computational systems expert Dan Jacobson analyzed billions of genetic data points from the lung cells of nine COVID-19 patients. It took Summit seven days to sort through data that traditional desktop computers would have spent months dissecting.

Jacobson said in a statement that he had a “eureka moment” when he noticed some “very distinct patterns” in the data from the patients’ bradykinin systems.

While cytokines fight off infection by attracting white blood cells and ultimately regulating the body’s temperature, bradykinins handle it via methods including inflammation. They’re responsible for sneezes, coughs, stuffy noses and other typical symptoms of influenza and the common cold. They’re also able to dilate blood vessels, making them porous.

Like cytokines, bradykinins can wind up in overdrive. Jacobson and his team say the genetic data from COVID-19 patients’ lungs includes an abundance of enzymes that can trigger the production of bradykinins and unexpectedly few enzymes that can break it down – what they described as the perfect conditions for a bradykinin storm, allowing for fluid to build up around the lungs.

“Immune cells that are normally contained in the blood vessels flood into the surrounding infected tissue, causing inflammation,” Jacobson said.

If this is happening in the lungs, the researchers theorize, it could also be taking place in other parts of patients’ bodies, causing everything from muscle pain to nausea to diarrhea as blood vessels leak due to the “out-of-control cascade” of bradykinin production.

If bradykinin storms are in fact responsible for some of the complications experienced by COVID-19 patients, then at least 10 existing drugs could be repurposed to treat those patients, Jacobson said, although only after extensive clinical trials.

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