Researchers Radboudumc: essential mechanism covid-19 exposed

Researchers at Radboud Hospital in Nijmegen think they have discovered an essential mechanism in the covid-19 disease process that has so far been overlooked.

“If the insight is correct, it probably has important consequences for the treatment of the disease,” says a press statement from the hospital.

Leaky blood vessels

Doctors always see three stages in severe infections with the coronavirus: shortness of breath due to fluid on the lungs, an inflammatory reaction in the lungs and the development of thrombosis and scarring in the lungs due to the fluid.

“The first phase, in which the lungs fill up with fluid, CT scans of the lungs look serious and patients quickly become short of breath when administering fluid, is very characteristic,” says Frank van de Veerdonk, internist-infectiologist at Radboud university medical center. “This picture cannot be explained only by the infection of the lungs. We had the idea that during this process the very small blood vessels in the lungs also leak. That leakage causes problems for the lungs, because they partly fill up.”

This was previously seen with SARS, the virus infection that claimed many lives in 2003. However, a good explanation was never found.

Possible leakage explanation

The researchers at Radboud university medical center now come up with a possible explanation for the leak. Covid-19 is known to enter the lungs through the so-called ACE2 receptor. ACE2 is an enzyme found on organs, including the lungs. It is also the receptor, the ‘receiver’, for the coronavirus in the human body.

“The virus binds to the receptor and is withdrawn by the receptor into the lung cell, where the virus can multiply,” says Van de Veerdonk. “In a massive infection, those ACE2 receptors disappear from the outside of the cell. Their function also disappears.”

Until now, doctors have known that ACE2 plays a role in maintaining blood pressure throughout the body. But it has another function, according to the researchers, which has been left out of the picture in covid-19 infections. “ACE2 keeps the substance bradykinin under control. Bradykinin makes blood vessels leak. We have good reason to believe that with these covid-19 infections we see exactly this effect: ACE2 receptors disappear from the lung cells by the introduction of the virus , which gives bradykinin free rein and causes the small blood vessels to leak en masse at the site of infection. “

Therapy

The researchers believe that this is an essential mechanism in the disease process of Covid-19. While most covid-19 treatments are now aimed at inhibiting inflammation, this research focuses on the phase before that: the leak that is causing the lungs to get into trouble.

That is why the researchers are already setting up treatments with icatibant, a drug that can inhibit the effects of bradykinin. “The beauty is: every patient is the same,” says Van de Veerdonk. “They all have no defenses and everyone is leaking. We have now started the treatment with five patients and I can be cautiously positive. But of course we are not there yet.”

International research must show whether the new insights and treatments do indeed have an effect. If that is the case, then this has major consequences, according to Van de Veerdonk. “The moment a patient enters the hospital, the whole process can be stopped within a few days and they will have an opportunity to clear the virus in the next two weeks. People can go home faster and because we asked patients no longer end up in intensive care. “

The researchers’ new insights have yet to be assessed and commented by colleagues. Van de Veerdonk chose to publish the research as soon as possible and not wait for publication in a highly regarded magazine. “Because if what we think is right, it can make all the difference.”

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