Genetic risks for severe COVID identified by scientists in 'stunning' research that paves the way for new treatments

Scientists have discovered a set of genes that may be linked to the onset of severe coronavirus complications.

Scientists from the University of Edinburgh analysed the DNA of more than 2,000 coronavirus patients in 208 intensive care units across the UK.

This genetic information was compared against samples provided by hundreds of thousands of healthy volunteers who took part in previous studies.

Results suggest variants of five genes may partially explain why some people become critically ill with the coronavirus, while others escape unscathed, not even developing mild symptoms.

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Existing drugs that target these genes, like one used to treat rheumatoid arthritis, could be repurposed to ease severe coronavirus complications, according to the scientists.

Although further research is required before these treatments can be prescribed, one of the scientists behind the study called the results “stunning”.

“This is a stunning realisation of the promise of human genetics to help understand critical illness,” said lead author Dr Kenneth Baillie.

“Just like in sepsis and influenza, in COVID-19 [the disease caused by the coronavirus], damage to the lungs is caused by our own immune system [over-reacting], rather than the virus itself.

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

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“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.”

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Early research suggests four out of five coronavirus cases are mild, with the majority of patients enduring moderate symptoms – or none at all – that do not require treatment.

At the start of the pandemic, critically-ill patients were offered supportive care like ventilation that helped to keep them alive while their immune system worked to fight off the infection naturally.

Studies have since found steroids can cut the risk of death among seriously-ill coronavirus patients by up to a third, prompting the NHS to start using versions of the low-cost drugs.

Research has so far failed to find any benefit for a range of treatments tested on milder cases of the infection.

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It has long been known that a person’s DNA influences their risk of becoming seriously ill with a range of infections.

To better understand the role of genetics in COVID-19, the Edinburgh scientists analysed thousands of patients in intensive care with coronavirus complications.

These genetic samples were compared against those from patients who took part in previous studies, like the UK Biobank.

The results – published in the journal Nature – suggest variants to the genes IFNAR2, TYK2, OAS1, DPP9 and CCR2 may be responsible for cases of severe illness.

Between 6% and 68% of people are thought to have one of these variants. The scientists stressed, however, there are likely rarer variants that also have an effect but are yet to be discovered.

Results ‘allow us to accelerate therapeutic approaches’

With certain genetic variants responding to particular drugs in a specific way, the scientists then predicted which treatments may be most effective for these individuals.

A reduction in TYK2’s activity, for example, was found to protect against COVID-19.

Anti-inflammatory drugs called Jak inhibitors – like baricitinib, which is commonly prescribed for rheumatoid arthritis – are known to inhibit TYK2.

The scientists also found a boost to INFAR2’s activity will likely confer protection due to the gene mimicking proteins called interferon, which are released by immune cells in response to a virus.

Treatments that boost INFAR2 may have to be given early in the disease’s onset, stressed the scientists.

They hope their results will lead to studies that test different drugs’ effectiveness against the coronavirus.

“We must do clinical trials before we change anyone’s clinical practice,” said Dr Baillie.

Dr Jonathan Pearce from the Medical Research Council – which partially funded the research – added: “Identifying genes associated with severe COVID-19, including in young patients without known underlying health issues, will allow us to better target and accelerate research into new diagnostic and therapeutic approaches.”

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