A team of scientists at the University of Oxford have made a major discovery about Covid-19, identifying the gene that puts people at double the risk of respiratory failure from the virus.
And worryingly, some communities are more likely to carry it than others.
Among those with South Asian ancestry, 60% carry the genetic signal – which may go some way to explain the excess deaths from Covid seen in some UK communities, and the impact of the virus in the Indian subcontinent.
Previous research had identified a stretch of DNA that doubled the risk of adults under 65 dying from Covid, but scientists did not know how this genetic signal caused the effect.
For this new study, the Oxford team led by Professors James Davies and Jim Hughes at the MRC Weatherall Institute of Molecular Medicine, trained an AI algorithm to analyse vast amounts of genetic data in hundreds of cell types from the body to find the genetic signal likely to affect cells in the lung.
Using a new and highly accurate technique, the researchers were able to zoom down on the DNA at the genetic signal to pinpoint the specific gene being controlled by the sequence and therefore responsible for increasing your risk of developing severe Covid-19.
Co-lead Prof Davies 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.
“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,” he explained.
While 60% of South Asians carried this higher-risk version of the gene, 15% of those with European ancestry did too. However, the authors of the study, published in Nature Genetics, stressed they are not suggesting socio-economic factors aren’t also important in determining Covid risk and outcome.
The Oxford researchers found the higher risk version of the gene is likely to prevent the cells lining airways and the lungs from responding to the virus properly.
However, it doesn’t affect the immune system – so researchers expect people carrying this version of the gene to respond normally to Covid vaccines.
The researchers are also hopeful that 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.
“The genetic factor we have found explains why some people get very seriously ill after coronavirus infection,” said Prof Davies. “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 Afro-Caribbean ancestry carried the higher risk genotype – meaning this genetic factor doesn’t fully explain the higher death rates reported for Black and minority ethnic communities.
Prof Davies explained: “The higher-risk DNA code is found more commonly in some Black and minority ethnic communities but not in others. Socioeconomic factors are also likely to be important in explaining why some communities have been particularly badly affected by the Covid-19 pandemic.
“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.”