Researchers Discover Specific Genetic Signals in People Who Develop Severe COVID-19

Researchers at the University of Sheffield and Stanford University in the United States have discovered that people with severe coronavirus infections have specific genetic signals.

Although age, obesity index, and existing health problems are known to be responsible for some disparities, genetics also plays an important role. This pioneering study aims to address the reasons why some people with COVID-19 become seriously ill or die, while others have few, if any, symptoms.

Using machine learning, researchers at the University of Sheffield and Stanford University have identified more than 1,000 genes associated with the development of severe COVID-19 cases that require respiratory support or are fatal. The team was also able to identify certain types of cells on which those genes act. This is one of the first studies to link coronavirus-related genes to specific biological functions.

During the study, he discovered the underlying genetic structure of coronavirus infection and found that these 1,000 genes make up three-quarters of the genetic drivers for severe COVID-19. This is important for understanding why some people have worse symptoms of Covid-19 than others. “

Dr. Jonathan Cooper Knock, NIHR Clinical Lecturer, University of Sheffield Neuroscience, Co-author of the study

Studies published in the journal today (June 14, 2022) Cell system, Professor Michael P. Snyder, senior author at Stanford University, led with genetics instructor Dr. Sai Chan and neuroscientist Dr. Cooper Knock (currently a visiting scholar at Stanford).

Survey process

The research team used several large datasets to elucidate the genetics behind the serious COVID-19. The first dataset contained genetic information from healthy human lung tissue. This data helped identify gene expression in 19 lung cells, including epithelial cells, which line the airways and are the first defense against infection.

Other data are from the COVID-19 HostGenetics Initiative, one of the largest genetic studies in patients with severe coronavirus. Researchers searched the data for genetic clues (DNA mutations called single nucleotide polymorphisms). This may indicate if someone is at high risk for severe COVID-19. They tracked whether some mutations occurred more or less frequently in COVID-19 patients with severe illness.

Mutations that continued to appear or were not specifically seen in patients with severe COVID-19 suggested that those changes may be behind the severity of the infection.

However, gene mutations themselves can be difficult to interpret. To better understand their findings, the team used other data to explain which regions of the genome are important for the different cell types in lung tissue. By overlapping the mutations with the cell-specific genome, researchers were able to identify which genes were dysfunctional and within which cell type.

Risk gene

Researchers also wanted to know which type of cell had the wrong gene expression.Through machine learning tools, they have severe COVID-19 with natural killer (NK) cells. T cells.. NK cells and a subtype called “CD56 Bright” are considered to be the most important.

Dr. Cooper Knock added: “When humans are born, NK cells, the body’s first line of defense against infection, are known for their ability to destroy viruses and cancer cells. NK cells are cytokines. One cytokine, interferon gamma, is an immune cell. NK cells, which act in concert with interferon gamma, provide immediate and coordinated defense against viral infections.

“NK cells are like generals who command war. They mobilize other immune cells to tell them where to go and what to do. In people with severe coronavirus infections, NK cells are important. We found that the gene was underexpressed, so it was found to be underexpressed. A strong immune response. The cells are not functioning as they should. “

Professor Snyder likened the COVID-19 risk gene to a deleterious variant of the BRCA gene that makes some people more susceptible to breast and ovarian cancer.

Professor Snyder said: “Our findings laid the foundation for genetic testing to predict who is at high risk for severe COVID-19.

“Imagine that there are 1,000 changes in the DNA associated with severe COVID-19. If these changes are 585, it can be quite susceptible and take all necessary precautions. is needed.”

Dr. Coopernock also said that drugs that slow down NK cells have already been proposed to treat certain types of cancer. “The drug binds to receptors on NK cells and induces them to respond more strongly,” he said. Testing of NK cell infusion for severe COVID-19 is underway. “