Gene that doubles risk of respiratory failure from Covid identified

Researchers have identified the gene responsible for doubling the risk of respiratory failure from coronavirus.

About 60% of people with south Asian ancestry carry the high-risk genetic signal, a new study found.

Scientists say this partly explains the excess deaths experienced in some UK communities, and the impact of Covid-19 in the Indian subcontinent, but stress that they are not suggesting that socioeconomic factors are not important for Covid risk and outcome.

The gene is also common in the European population, occurring in about 15%.

Study co-lead Prof James Davies, who worked as an NHS consultant in intensive care medicine during the pandemic and is an associate professor of genomics at Oxford University’s Radcliffe Department of Medicine, said:

If you have the high-risk genotype and you get very unwell with Covid, there’s a 50% chance that that wouldn’t have happened to you had you had the lower-risk genotype.

The study, published in Nature Genetics, also found that the gene does not alter immune cell function.

Because the effect is in the biology of the lungs, people with the higher-risk version of the genes should respond fully to vaccination, the scientists say.

Previous research had identified a stretch of DNA on chromosome three that doubled the risk of adults under the age of 65 from Covid. But it was not known how this genetic signal worked to increase the risk, nor the exact genetic change that was responsible.

Study co-lead Prof Jim Hughes, professor of gene regulation at the University of Oxford, said:

The reason this has proved so difficult to work out, is that the previously identified genetic signal affects the ‘dark matter’ of the genome. We found that the increased risk is not because of a difference in gene coding for a protein, but because of a difference in the DNA that makes a switch to turn a gene on. It’s much harder to detect the gene which is affected by this kind of indirect switch effect.

The gene was identified using a combination of artificial intelligence and cutting-edge molecular technology, which visualises the structure of DNA inside cells in unprecedented detail.

Dr Damien Downes, who led the laboratory work from the Prof Hughes research group, said:

Surprisingly, as several other genes were suspected, the data showed that a relatively unstudied gene called LZTFL1 causes the effect.

The researchers found that the higher-risk version of the gene probably prevents the cells lining airways and the lungs from responding to the virus properly.

They hope drugs and other therapies could target the pathway preventing the lung lining from transforming to less specialised cells, raising the possibility of new treatments customised for those most likely to develop severe symptoms.

Davies said:

The genetic factor we have found explains why some people get very seriously ill after coronavirus infection. It shows that the way in which the lung responds to the infection is critical. This is important because most treatments have focused on changing the way in which the immune system reacts to the virus.

The study also found that 2% of people with African-Caribbean ancestry carried the higher-risk genotype, meaning this genetic factor does not completely explain the higher death rates reported for black and minority ethnic communities.

Davies added:

Although we cannot change our genetics, our results show that the people with the higher risk gene are likely to particularly benefit from vaccination. Since the genetic signal affects the lung rather than the immune system it means that the increased risk should be cancelled out by the vaccine.

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UK records 214 deaths and 37,269 new infections

A further 214 deaths within 28 days of a positive Covid test have been recorded in the past 24 hours in the UK, and another 37,269 new cases reported, according to the latest figures from the government dashboard.

This compares with 41,299 cases and 217 deaths reported the day before.

Cases Soar in Europe

Europe registered a 55% rise in Covid cases in the last four weeks, despite the availability of vaccines, which should serve as a “warning shot” to other regions, World Health Organization (WHO) officials said on Thursday.

WHO emergency director Mike Ryan said that some European countries had “suboptimal vaccination coverage” despite availability.

“It’s a warning shot for the world to see what is happening in Europe despite availability of vaccination,” Ryan told a news conference.

WHO chief scientist Soumya Swaminathan said that Indian drugmaker Bharat Biotech’s Covaxin showed about 70% efficacy against the Delta variant. The WHO said on Wednesday that it has granted approval for its emergency use listing.

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WORLD STATS

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