By overlapping the mutations onto the cell-specific genomes the researchers could pinpoint which genes were dysfunctioning and within which cell-types.
The researchers also wanted to know which types of cells harboured faulty gene expression. Through their machine learning tool, they determined that severe COVID-19 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.
Doctor Cooper-Knock added: “NK cells, which humans are born with and are the body’s first line of defence against infection, are known for their ability to destroy viruses and cancer cells. NK cells also help produce a range of immune system proteins called cytokines. One cytokine, interferon gamma, is a key activator of immune cells. Acting in concert with interferon gamma, NK cells mount an immediate and coordinated defence against viral infections.
“NK cells are like the generals directing the war. They mobilize other immune cells, telling them where to go and what to do. We found that in people with severe coronavirus infection, critical genes in NK cells are expressed less, so there’s a less robust immune response. The cell isn’t doing what it’s supposed to do.”