Covid: Genes hold clues to why some people get severely ill

Why some people with coronavirus have no symptoms and others get extremely ill is one of the pandemic's biggest
puzzles.

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

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

The findings shed light on where the immune system goes wrong, which could help identify new treatments.

These will continue to be needed even though vaccines are being developed, says Dr Kenneth Baillie, a consultant
in medicine at the Royal Infirmary in Edinburgh, who led the Genomicc project.

"Vaccines should drastically decrease the numbers of covid cases, but it's likely doctors will still be treating the disease
in intensive care for a number of years around the world, so there is an urgent need to find new treatments."

'Angry' cells

Scientists looked at the DNA of patients in more than 200 intensive care units in UK hospitals.

They scanned each person’s genes, which contain the instructions for every biological process - including how to fight
a virus.

Their genomes were then compared with the DNA of healthy people to pinpoint any genetic differences, and a number
were found - the first in a gene called TYK2.

“It is part of the system that makes your immune cells more angry, and more inflammatory,” explained Dr Baillie.

But if the gene is faulty, this immune response can go into overdrive, putting patients at risk of damaging lung
inflammation.

Too little interferon

Genetic differences were also found in a gene called DPP9, which plays a role in inflammation, and in a gene called
OAS, which helps to stop the virus from making copies of itself.

Variations in a gene called IFNAR2 were also identified in the intensive care patients.

IFNAR2 is linked to a potent anti-viral molecule called interferon, which helps to kick-start the immune system as
soon as an infection is detected.

It’s thought that producing too little interferon can give the virus an early advantage, allowing it to quickly replicate,
leading to more severe disease.

Two other recent studies published in the journal Science have also implicated interferon in Covid cases,
through both genetic mutations and an autoimmune disorder that affects its production.

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