Why are some healthy people dying from Covid-19?

Why are people dying from Covid-19? Why do some young people without concomitant diseases die from the disease, while others, the elderly, survive? It was these ambitious questions that the French physician and researcher Paul Bastard wanted to try to answer. This pediatrician, a member of the Imagine Research Laboratory in Paris, has been involved in two major studies published in The science, which show that 15% of severe forms of Covid-19 are actually due to genetics. 22 variants affecting 8 different genes have a detrimental effect on the immune system’s response to Covid-19. The work that won him the 2022 Science for Immunology Award today. Interview.

Science and the future: “Why are people dying from Covid-19?“, that’s the big question you wanted to answer. Why did you decide to tackle this topic?

Paul Bastard: When the pandemic started, I was working as an intern in hospitals in Paris. It was necessary to quickly respond to the influx of patients infected with Covid-19. My wife was then working at the Lariboisière hospital, which needed reinforcements, and where I, like many others, came to lend a helping hand. We were faced with a new type of patient, not understanding why some of them had severe forms and died from it when there were no comorbidities such as diabetes or obesity.

How did you start your research?

At that time, I was writing a scientific thesis – in parallel with the study of medicine – at the Institute of the Imagination with professors Jean-Laurent Casanova and Laurent Abel from the Institute of the Imagination in Paris (Necker Hospital – Sick Children, AP-HP). I was trying to figure out why some infections were more severe in some than in others. For two years now, I have been working on the genetic predisposition to severe viral infections that often affect children. Affected by genetic defects, they cannot protect themselves from certain infections. So we decided to ask the same question about Covid-19.

At that time, France was imprisoned and suddenly stopped. What solutions have you found to get your job done?

We were in complete captivity, everything was closed. Jean-Laurent Casanova set up a consortium to recruit patients, but he did not have a sample carrier. Therefore, it was I who traveled from hospital to hospital on a bicycle, to the intensive care units of Paris and the surrounding suburbs to collect blood samples. I kept them in special boxes in my backpack and crossed the deserted Paris on my two-wheeled bicycle. Once they arrived at the lab, DNA had to be extracted from the samples and then sequenced. We started this work by recruiting physicians from over 40 countries with huge cohorts. Without them, none of this would have been possible.

Jean-Laurent Casanova of the Imagination Institute and Rockefeller University then launched the COVID Human Genetic Effort (CHGE) project and also partnered with the Howard Hughes Medical Institute in New York to use these DNA tests. What did you observe in these samples?

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