The world’s largest genetic study reveals fresh details about severe Covid-19

The world’s largest study of important Covid-19 genetics involving more than 57,000 people reveals fresh details about some of the biological mechanisms behind the severe form of the disease.

Approximately 16 new genetic variants associated with severe Covid-19 have been identified, including those associated with blood clotting, immune response, and intensity of inflammation.

Experts say these findings will serve as a roadmap for future efforts and open up new research areas with pinpoint accuracy and a focus on potential new therapies and diagnostics.

Researchers at the GenOMICC Consortium, a global collaboration to study the genetics of critical diseases, led by the University of Edinburgh in partnership with Genomics England, sequenced the genomes of 7,491 patients from 224 intensive care units in the United Kingdom. We made these discoveries by making decisions.

Their DNA was compared to another 48,400 people who did not have Covid-19, participants in the 100,000 Genomes Project at Genomics England, and an additional 1,630 people who experienced mild Covid.

By determining the entire genomic sequence of all participants in the study, the team was able to create an accurate map and identify genetic variation associated with the severity of Covid-19. The team found significant differences in the 16 genes in ICU patients when compared to the DNA of other groups.

They also confirmed the involvement of seven other genetic variants already associated with severe Covid-19 found in previous studies from the same team.

The findings show how a single gene variant (called interferon alpha-10) that disrupts a major messenger molecule in immune system signaling is sufficient to increase a patient’s risk of serious illness. Something was included.

This highlights the important role of genes in the immune system, and treating patients with interferon, a protein released by immune cells to protect against the virus, may help manage early-stage disease. It suggests that.

The study also found that mutations in the genes that control the levels of central components of blood clotting (known as factor VIII) are associated with a serious disease of Covid-19.

This may explain some of the coagulation abnormalities found in severe cases of Covid-19. Factor VIII is the underlying gene for the most common type of hemophilia.

Professor Kenneth Bailey, Principal Investigator of the project and consultant for emergency medicine at the University of Edinburgh, said: Others have no symptoms at all, but more importantly, this is a great step forward to give us a deeper understanding of the process of illness and to find more effective treatments.

“Now we have a better understanding of Covid’s mechanism than other syndromes treated with conventional intensive care, such as sepsis, flu, and other serious illnesses. Covid-19 knows how to tackle these. Shows. Future issues. “

Professor Mark Caulfield, a former chief scientist at Queen Mary University of London and co-author of the study, said: Throughout all genome sequencing research, we have discovered new genetic variants that make people more susceptible to serious illness. This provides a path to new tests and treatments that help protect the general public and the NHS from this virus. “

Strategically, genomics is at a stage where it is becoming an integral part of the country’s infrastructure in everyday medicine. This study demonstrates the value of whole-genome sequencing for detecting rare and common mutations that affect serious illnesses that require intensive care. This represents a major leap forward in understanding how our genetic makeup affects the severe disease of Covid-19.

All those involved in the study have made great efforts to engage with all communities in the UK, including groups that have historically been undervalued in medical research. The inclusive elements of our work have produced meaningful results for everyone in the country. “

Dr. Rich Scott, Chief Medical Officer, Genomics England

Sir Camor, Minister of Innovation at the Department of Health (DHSC), said: We can provide world-class care.

“This study is an important step in better understanding the impact of Covid-19 on certain people, enabling them to take the necessary actions to protect the most vulnerable and save lives. increase.”

The survey results are published in Nature.

GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) is an open, global consortium of intensive care clinicians dedicated to understanding the genetic factors that influence the outcome of intensive care for diseases such as SARS, influenza and sepsis. Started in 2015 as.

The consortium is led by the University of Edinburgh and has been working with Genomics England since 2020 to focus on Covid-19 research in collaboration with NHS Lothian, Intensive Care National Audit and Research Center (ICNARC), and Queen Mary University. I am. Of London.

The groundbreaking 100,000 Genome Project was established in 2014 to sequence 100,000 genomes from people with rare diseases and cancer. The project was completed in 2018, paving the way for the creation of new genomic medical services for the NHS England and transforming patient care by providing advanced diagnostics and personalized treatment.

GenOMICC is funded by DHSC, LifeArc, the charity Sepsis Research FEAT, the Intensive Care Society, Wellcome, UK Research and Innovation, the Chief Scientist Office in Scotland, the Department of Health and the National Institute for Health Research (NIHR). Supported by Illumina.