Researchers discover new insights into severe COVID-19

• Researchers identified 16 new genetic variants associated with severe Covid-19
• This included some genetic variants 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.

Researchers sequenced the genomes of 7,491 patients from 224 intensive care units in the UK, including GOSH.

Their DNA was compared with:

• 48,400 other people who had not had Covid-19
• participants in Genomics England's 100,000 Genomes Project
• a further 1,630 people who had experienced mild Covid-19.

By understanding the whole genome sequence for all participants in the study, the team were able 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 patients with severe Covid-19, when compared with the DNA of the other groups. They also confirmed the involvement of seven other genetic variations already associated with severe Covid-19, which were discovered in earlier studies from the same team.

The study was conducted with the support of researchers from the GenOMICC consortium. The GenOMICC consortium is a global collaboration to study genetics in critical illness and involves teams in the Intensive Care Unit (ICU) at GOSH. These researchers were led by University of Edinburgh in partnership with Genomics England.

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

The study also found that variations in genes that control the levels of a central component of blood clotting – known as Factor 8 – were associated with critical illness in Covid-19.

This study was in adults and children and, while children made up a much smaller proportion of those studied (severe response to SARS-CoV-2 in children is much rarer than for adults, and includes a new syndrome called PIMS-TS), their inclusion meant that the study was able to examine how age affected the disease severity, a crucial part of the study.

"This projects is an incredible example of what can be achieved by the NHS research community through collaboration on this scale, at speed," explains Dr Jenny Rivers, Deputy Director of Research and Innovation.

"Early findings from this study have already helped the RECOVERY study (a collaboration between multiple UK research organisations and hospitals, including GOSH) pick interventions that target Covid-19 based on a patient's genetics. Building on prior studies and working with others so quickly and closely as part of a bigger initiative, highlights the power of Research Hospitals, like GOSH, to deliver patient benefit in such a short timescale."

GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) 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. The consortium is led by the University of Edinburgh, and since 2020 it has been focused on Covid-19 research.

GenOMICC is funded by DHSC, LifeArc, the charity Sepsis Research FEAT, the Intensive Care Society, Wellcome, UK Research and Innovation, Scotland’s Chief Scientist Office, the Department of Health and Social Care and the National Institute for Health Research (NIHR), and supported by Illumina, and all research at GOSH is underpinned by the NIHR GOSH BRC.

The findings have been published in Nature.