The cholesterol trail elucidated

Since the beginning of the pandemic, several studies have shown that statins, cholesterol-lowering drugs, protect against severe COVID-19. Montreal researchers have just figured out why.

“The largest study on statins and COVID-19 showed a protective effect of 50%,” says Nabil Seidah, biologist at the Montreal Clinical Research Institute (IRCM) and lead author of the new study published in February. in the review Viruses. “It’s huge, and it remained mysterious. Our study has just explained the effect of statins. »

More than half a million Quebecers take statins to lower their cholesterol levels, according to Statistics Canada.

PCSK9 protein

The IRCM biologist elucidated the mystery thanks to his decades of work on the PCSK9 protein, which plays an important role in cholesterol levels. Mr. Seidah discovered PCSK9 in 2003.

“Statins increase PCSK9 levels at the same time as they lower cholesterol levels,” says Seidah. We have just demonstrated that PCSK9 degrades the receptor by which SARS-CoV-2 [le coronavirus responsable de la COVID-19] enters human cells. »

To complicate matters, an American study which has just been published in the Log from the American College of Cardiology has shown that antibodies to the PCSK9 protein help recover patients hospitalized with COVID-19. “It was really troubling, because it went against our results,” says Seidah. It was a small study, on just 60 hospitalized patients, but the results were still strong. »

The sleuthing work of IRCM researchers has solved this second mystery. “PCSK9 prevents infection, but once the patient is sick, it has a detrimental effect on the course of COVID-19,” says Seidah. This is because PCSK9 has an inflammatory effect. And the main problem with severe COVID is inflammation. »

Hypercholesterolemia

Dr. Seidah’s work on PCSK9 made it possible half a dozen years ago to treat patients who suffered from “familial hypercholesterolemia” with very high cholesterol levels. Statins do not cure familial hypercholesterolemia.

This treatment for familial hypercholesterolemia involves drugs – antibodies – that attack PCSK9, because this molecule in some cases raises cholesterol levels. A few tens of thousands of Quebecers, including patients intolerant to statins, take these “PCSK9 inhibitor” drugs.

The pressing question is therefore whether patients who take PCSK9 inhibitors are at higher risk of being infected with COVID-19. “It’s going to be difficult to determine, but it would be really interesting to find out,” says the D^r Seidah.