Stockport NHS Foundation Trust’s Research and Innovation team has contributed towards providing important new insights into the biological reasons why some people develop more severe symptoms from COVID-19.

The GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) study was the world’s largest ever of its kind into the genetics of critical COVID-19, involving more than 57,000 people, including more than 200 recruited to date from the Stockport area. Stockport has been one of the leading recruiters in the UK for this trial during the pandemic. This study was part of the wider GenOMICC genetic research project which is also working towards new treatments for sepsis, influenza and other forms of critical illness as well.

The research has revealed fresh details about some of the biological mechanisms behind the severe form of the disease, and has helped to identify 16 new genetic variants associated with severe COVID-19, including some related to blood clotting, immune response and intensity of inflammation.

These findings will act as a roadmap for future efforts, opening new fields of research focused on potential new therapies and diagnostics with pinpoint accuracy, experts say.

A genome is a unique sequence of DNA. Over 3 billion letters long, it is found in almost every cell in the human body. Analysis can be performed to provide the biological or medical meaning of this sequence, including how it can be used to help prevent disease; in this case COVID-19. Researchers from the GenOMICC consortium – a global collaboration to study genetics in critical illness – led by University of Edinburgh in partnership with Genomics England, sequenced the genomes of 7,491 patients from 224 intensive care units in the UK, including at Stepping Hill Hospital.

Their DNA was compared with 48,400 other people who had not had COVID-19, participants in Genomics England`s 100,000 Genomes Project, and that of a further 1,630 people who had experienced milder versions of the infection.

Determining the whole genome sequence for all participants in the study allowed the team to create a precise map and identify genetic variation linked to severity of COVID-19. The team found key differences in 16 genes in the ICU patients when compared with the DNA of the other groups.

The findings included how a single gene variant that disrupts a key messenger molecule in immune system signaling – called ‘interferon alpha-10’ – was enough to increase a patient’s risk of severe disease.

This highlights the gene’s key role in the immune system and suggests that treating patients with interferon – proteins released by immune cells to defend against viruses – may help manage disease in the early stages.

Professor Kenneth Baillie, the project’s chief investigator and a Consultant in Critical Care Medicine at University of Edinburgh, said: “Our latest findings point to specific molecular targets in critical COVID-19. These results explain why some people develop life-threatening COVID-19, while others get no symptoms at all. But more importantly, this gives us a deep understanding of the process of disease and is a big step forward in finding more effective treatments.

“It is now true to say that we understand the mechanisms of Covid better than the other syndromes we treat in intensive care in normal times – sepsis, flu, and other forms of critical illness. COVID-19 is showing us the way to tackle those problems in the future.”

Dr Ahmed Zaki and Dr Matt Jackson are the lead investigators for the trial at Stockport NHS Foundation Trust. Dr Ahmed Zaki said: “We are very pleased to have been able to contribute towards the important new findings of this research, which we hope will play a key role in reducing the number of people getting seriously ill and being hospitalised through COVID-19. We’d like to thank everyone who has helped with this, including all the volunteers and both our research and ICU colleagues at the trust.”