An international team of researchers has discovered specific genetic signals in people who develop severe coronavirus infection.

Using machine learning, researchers from the University of Sheffield and Stanford Medicine identified more than 1,000 genes linked to the development of severe COVID-19 cases that required breathing support or were fatal.

"During the research, we discovered the genetic architecture underlying coronavirus infection and found that these 1,000 genes account for three-quarters of the genetic drivers for severe COVID-19.

This is significant in understanding why some people have had more severe symptoms of COVID-19 than others," said Dr Johnathan Cooper-Knock, NIHR Clinical Lecturer in the Department of Neuroscience at Sheffield.

In the study, published in the journal Cell Systems, the team used several large data sets to unpack the genetics behind severe COVID. The first data set contained genetic information from healthy human lung tissue.

The data helped identify gene expression in 19 different types of lung cells, including epithelial cells that line the respiratory tract and are the first defence against infection.

Other data came from genetic studies of critically ill coronavirus patients. The researchers looked for genetic clues in the data -- DNA mutations, called single nucleotide polymorphisms -- that might indicate if someone is at a higher risk for severe COVID. They tracked whether some mutations occurred more or less often in COVID patients with severe diseases.

Mutations that continued to appear, or were notably absent, in the patients who developed severe COVID suggested those variations might be behind the infection's severity.

The researchers also wanted to know which types of cells harboured faulty gene expression. Through their machine learning tool, they determined that severe COVID is largely associated with a weakened response from two well-known immune cells - natural killer (NK) cells and T cells. NK cells and a subtype called 'CD56 bright' are considered the most important.

Professor Michael P. Snyder from Stanford likened COVID risk genes to harmful variants of the BRCA genes that predispose some people to breast and ovarian cancer.

"Our findings lay the foundation for a genetic test that can predict who is born with an increased risk for severe COVID-19. Imagine there are 1,000 changes in DNA linked to severe COVID-19. If you have 585 of these changes, that might make you pretty susceptible, and you'd want to take all the necessary precautions," Snyder said