Study reveals new genetic variants in severe Covid patients

Royal Brompton and Harefield hospitals have contributed to the world’s largest study of the genetics of critical Covid-19, revealing 16 new variants that predispose patients to critical illness.

The genes identified by the research, led by scientists from Genomics England and the University of Edinburgh, are linked to immune system signalling, alongside blood clotting and lung inflammation — some of the hallmarks of severe Covid. They also confirmed seven other genes associated with severe Covid identified by earlier research.

Dr Anna Reed, consultant in respiratory and transplant medicine, was the principal investigator at Harefield Hospital for the GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) study, which could aid the development of new treatments.

“Our research teams worked exceptionally hard throughout the pandemic to contribute valuable patient samples and data to this national project.”

She described the study, published in Nature this week, as “an enormously important piece of work that provides early insights into why some people develop life-threatening Covid-19 and others don’t.

“This study is the first step towards developing newer therapies and identifying individuals at greatest risk.” 

The research, led by Dr Kenneth Baillie, a consultant in critical care medicine at the University of Edinburgh, identified genetic patterns by comparing the DNA of 7491 patients from 224 intensive care units in the UK with that of 1630 people who experienced mild Covid-19 symptoms,48,400 people who have never had Covid-19, and participants of the UK government’s 100,000 Genomes Project.

Dr Brijesh Patel, honorary consultant for the adult intensive care units, was the principal investigator at the Royal Brompton. He said: “To expand and deliver this study during the pandemic was an immense national effort led by Professor Kennie Baillie. The research will not only enable the development of therapies for Covid-19 but also other syndromes we treat in intensive care in normal times, leaving a lasting impact once the pandemic is over.”

Professor Sir Mark Caulfield from Queen Mary University of London, formerly chief scientist at Genomics England and co-author on the study, said: “Through our whole genome sequencing research, we’ve discovered novel gene variants that predispose people to severe illness, which now offer a route to new tests and treatments, to help protect the public and the NHS from this virus.”

According to Dr Rich Scott, chief medical officer at Genomics England, the study illustrates the value of whole-genome sequencing to detect rare and common variants that influence critical illness requiring intensive care.

“All those involved in the study went to great efforts to engage with all communities within the UK – including groups that have historically been under-represented in medical studies.” 

He added that the inclusive element of the work generated meaningful results for everyone in the country.

GenOMICC started in 2015 as an open, global consortium of intensive care clinicians dedicated to understanding genetic factors influencing outcomes in intensive care from diseases such as SARS, flu and sepsis, led by the University of Edinburgh and Genomics England, in collaboration with NHS Lothian, the Intensive Care National Audit and Research Centre (ICNARC), and Queen Mary University of London, and supported by Illumina.