More than 1,000 genes that are linked to the development of severe COVID-19 infection have been identified for the first time.
Researchers in the Department of Neuroscience at the University of Sheffield, UK, worked with colleagues at Stanford University, USA, to investigate why some people with COVID-19 become seriously ill or die, while others have few, if any, symptoms.
In what is one of the first studies to link coronavirus-associated genes to specific biological functions, they used machine learning and discovered more than 1,000 genes linked the severe disease that meant individuals need to have breathing support or who go on to die.
The study is published in *Cell Systems*.
Co-study author Dr Johnathan Cooper-Knock, a neuroscientist, NIHR clinical lecturer at the University of Sheffield and visiting scholar at Stanford, said: “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.”
The team examined several large data packs to uncover the gene association. The first data set contained genetic information from healthy human lung tissue, which helped to identify gene expression in 19 different types of lung cells.
Other data came from the COVID-19 Host Genetics Initiative, one of the largest genetic studies of critically ill coronavirus patients.
The research team looked for single nucleotide polymorphisms, which could indicate someone is at a higher risk for severe COVID-19, analysing this to see if some mutations occurred more or less often in patients with severe disease.
They went on to scrutinise other data that looked at regions of the genome which are important for different cell types within lung tissue. By overlapping the mutations onto the cell-specific genomes the team discovered the dysfunctioning genes and within which cell-types.
They also established that severe disease is significantly associated with a weakened response from natural killer (NK) cells – the most important type being the subtype CD56 bright – and T cells.
Dr Cooper-Knock said in people with severe coronavirus infection, critical genes in NK cells are expressed less, which results in a less robust immune response
He added drugs that kickstart sluggish NK cells are already proposed to treat some types of cancer and trials of NK cell infusions for severe COVID-19 are under way.
Professor Michael P Snyder, of the University of Stanford, said their 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,” he added.
Zhang S, Cooper-Knock J, Weimer AK et al. Multiomic analysis reveals cell-type-specific molecular determinants of COVID-19 severity. *Cell Systems* 14 June 2022
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