Experts identify five genes associated with severe illness in Covid-19 patients

Scientists have identified mutations in five genes associated with the development of life-threatening illness in patients with Covid-19.

UK researchers said their work, published in the journal Nature, sheds light on the mechanisms that underpin severe coronavirus symptoms and could lead to potential new drug treatments for the disease.

Dr Kenneth Baillie, the project’s chief investigator and senior research fellow at University of Edinburgh’s Roslin Institute, said: “This is a stunning realisation of the promise of human genetics to help understand critical illness.

“Just like in sepsis and influenza – in Covid-19 – damage to the lungs is caused by our own immune system, rather than the virus itself.

“Our genetic results provide a roadmap through the complexity of immune signals, showing the route to key drug targets.

“Our results immediately highlight which drugs should be at the top of the list for clinical testing.

“We can only test a few drugs at a time, so making the right choices will save thousands of lives.”

Dr Baillie and his team performed a genome-wide association study (GWAS) on 2,244 critically ill patients with Covid-19 from 208 intensive care units (ICU) in the UK.

GWAS is a commonly used study design which allows scientists to identify which genes are involved in human disease.

Working with experts from the GenOMICC consortium, a global collaboration looking into the links between genetics and critical illness, the researchers compared the genetic information of Covid-19 patients in ICU with samples provided by healthy volunteers from other studies.

The team found that variations in five genes – IFNAR2, TYK2, OAS1, DPP9 and CCR2 – was associated with the development of severe illness in Covid-19 patients.

The scientists said that they were able to pinpoint two molecular processes – antiviral immunity and lung inflammation – associated with the genes.

Innate antiviral defences are known to be important early in the disease while the inflammatory processes triggered by the infection are a key feature of severe Covid-19, the researchers said.

But the team said the research was not aimed at predicting who is likely to get critically ill with Covid-19 but focuses more on finding “biological clues that will lead us to effective treatments”.

The is because some patients with particular genetic variants are able to respond to certain drugs and the researchers believe genetic evidence could be used as a way to tell which treatments will be effective in a disease.

For example, they said, drugs that reduce the activity of the TYK2 gene could also help protect against Covid-19.

A class of anti-inflammatory drugs called JAK inhibitors, which includes the drug baricitinib, produces this effect, they added.

The researchers also said that the proportion of risk – the overall chance of becoming critically ill with Covid-19 – associated with the genetic variants is estimated to be around 6.5%.

They said that this is far less when compared to other known Covid-19 risk factors, such as age.

The team said further clinical trials should focus on drugs that target specific antiviral and anti-inflammatory pathways.

Dr David Strain, clinical senior lecturer at the University of Exeter, described the research as “incredibly interesting”.

But he added that the implications for the findings are limited, saying: “These data are useful for predicting those that are at risk, however the majority of us do not know what our genes look like.

“In the near future, however, the additional interest may arise from a greater understanding about what these genes do.

“A knowledge of what they do may lead to greater opportunities to develop future treatments.”

The minister for innovation, Lord Bethell, said: “Covid-19 is the biggest public health challenge we have faced in a century.

“As each day passes, we are learning more about this virus, supported by incredible advancements from scientists across the UK.

“As we pull together to tackle this unprecedented pandemic, it’s clear we are on the front foot with our research.

“Research like this is a big step forward in going further to advance our understanding of Covid-19 to help us protect the most vulnerable – ultimately saving lives across the world.”