Genes that help understand why some people get sicker than others

One of the biggest enigmas of the pandemic is understanding why some people with coronavirus have no symptoms, while others become seriously ill.

A study of more than 2,200 intensive care patients published in the journal Nature identified specific genes that may provide the answer.

They make some people more susceptible to severe Covid-19 symptoms.

The findings shed light on where the immune system is failing, which may help identify new treatments.

Treatments will remain necessary even as vaccines are developed, says Kenneth Baillie, a medical consultant at Royal Infirmary in Edinburgh, who led the project called Genomicc.

“Vaccines are expected to drastically decrease the number of cases, but clinicians will likely still need to treat the disease in intensive care for several years around the world. Therefore, there is an urgent need to find new treatments.”

‘Angry’ cells

The scientists analyzed the DNA of patients in more than 200 intensive care units in UK hospitals.

All of the patients underwent extensive analysis of their genes, which in turn contain instructions for all biological processes, including how to fight a virus.

The genomes of these people were then compared to the DNA of healthy people in an attempt to identify differences. Some have been found, the first in a gene called TYK2.

“It’s part of the system that makes immune cells more irritated and more inflammatory,” Baillie explained.

If the gene is flawed, that immune response can be depleted, putting patients at risk for severe lung inflammation.

One type of anti-inflammatory drug that is already used for diseases like rheumatoid arthritis targets exactly this biological mechanism. This is the case with a drug called Baricitinib.

“This makes it a very plausible drug candidate for new treatments,” Baillie said. “But of course we need to do large-scale clinical trials to find out whether this is confirmed or not.”

Small ‘interferon’

Genetic differences have also been found in a gene called DPP9, which plays a role in inflammation, and in a gene called OAS, which helps prevent the virus from multiplying.

Furthermore, variations in a gene called IFNAR2 have also been identified in intensive care patients.

IFNAR2 is linked to a powerful antiviral molecule called interferon, which helps activate the immune system as soon as an infection is detected.

It is believed that low interferon production can give the virus a head start, allowing it to replicate rapidly, leading to more serious conditions.

Two other recent studies published in the journal Sciences They have also linked interferon with cases of Covid, through genetic mutations and an autoimmune disorder that affects its production.

Professor Jean-Laurent Casanova, who conducted the research, at Rockefeller University in New York, said: “[Interferon] it was responsible for almost 15% of the critical cases of Covid-19 registered internationally according to our study. ”

Interferon could be given as a treatment, but a World Health Organization clinical trial concluded that it did not help critically ill patients. However, Professor Casanova says that context is important.

He explained: “I hope that if given within the first two, three or four days of infection, the interferon would work, because it would essentially supply the molecule that [paciente] it does not produce by itself “.

‘When things go wrong’

Vanessa Sancho-Shimizu, a geneticist at Imperial College London, said the genetic findings offer unprecedented insight into the biology of the disease.

“It’s really an example of precision medicine, where we can really pinpoint when things went wrong for that person,” he told BBC News.

“The findings from these genetic studies will help us identify specific molecular pathways that could be targets for therapeutic intervention,” he said.

But the genome still has some mysteries.

The Genomicc study, and several others, revealed a group of genes on chromosome 3 strongly linked to severe symptoms. However, scientists still don’t understand the biology behind this.

More patients will be invited to participate in the survey.

“We need everyone, but we are particularly interested in recruiting people from ethnic minority groups who appear more widely in the seriously ill population,” Baillie said.

He added: “There is still an urgent need to find new treatments for this disease and we have to make the right decisions about the next treatments, because we don’t have time to make mistakes.”