The world’s largest genetic study of people with severe COVID has identified DNA variations that could lead to life-saving new treatments for the disease.

The research identified 16 changes in the DNA sequence of critically ill COVID patients that affected their immune response or increased the risk of blood clotting and inflammation in the lungs.

Researchers from the GenOMICC consortium, which involved almost every intensive care unit in the UK, say the findings define new molecular targets for drugs currently used to treat other medical conditions.

Professor Kenneth Baillie, the study’s lead researcher and critical care consultant at the University of Edinburgh, said: “We have shown for the first time in the history of critical care medicine that a disease infection that causes organ failure can be treated by suppressing the immune system.

“That’s a reason to keep trying to treat covid better and reduce mortality to zero. That should be our goal.”

The researchers compared the full genetic sequence of nearly 7,500 critically ill patients with more than 48,000 people from the Genomics England database who had not had COVID, and another 1,630 who had mild symptoms.

Findings published in the journal Nature showed that 16 variations were significantly more common in people who suffered a poor outcome from the disease.

“Absolutely extraordinary”

An earlier study by the same researchers identified four genetic targets for treatment.

As a result, baricitinib, an anti-inflammatory drug normally used to treat rheumatoid arthritis, was tested in the NHS-led RECOVERY trial, with results showing it saved lives.

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“When we started this study, we were funded by a small charity founded by a group of relatives of a patient who died in intensive care and they generously supported us to start,” Professor Baillie said.

“I told them it could take more than 10 or 15 years to go from finding genes to impacting therapy.

“So to do it in just over a year is absolutely extraordinary.”

The human genetic code, or genome, has three billion letters. But simple substitutions with a different letter in key genes can change the blueprint of protein manufacturing.

One of the recently discovered variations involved a gene that makes interferon, a molecule used by cells to signal the immune system that an infection is present. Because the protein was folded in a slightly different way, the cells couldn’t raise the alarm.

Effective therapies

“This was significantly associated with the risks of dying with COVID,” Professor Baillie said.

The study was so successful in identifying drug targets that scientists are now tackling other major causes of death in critically ill patients, including sepsis or blood poisoning, in which the immune system reacts excessively to infection and attacks the organs of the body.

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More than 120 treatments for sepsis have been tested in trials over the past four decades, but without success.

Professor Baillie said: “GenOMICC has shown that we can find effective therapies for serious diseases using genetics.

“Embolished by this proof of concept, we will work as hard as we can. Our 10-year goal is to have a clinical impact on sepsis, but it may take longer than that.”