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1,000 Reasons COVID Can Kill Even A Healthy Person – New Research Just Found

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It is recognized that age, body mass index and pre-existing health conditions contribute to some of the disparities, but genes also play a substantial influence.

The goal of this groundbreaking study was to figure out why some patients with COVID-19 become extremely ill or die, while others have few or no symptoms at all.

Scientists at the University of Sheffield and Stanford Medicine used machine learning to pinpoint over a thousand genes that contributed to the emergence of severe COVID-19 cases that required respiratory support or were deadly. The researchers were also able to pinpoint the types of cells in which those genes are active. It’s one of the first studies to show a relationship between coronavirus-associated genes and biological processes.

“During the research,” says Dr. Johnathan Cooper-Knock, co-author of the study, “we discovered the genetic architecture underlying coronavirus infection,” and they “found that these 1,000 genes account for three quarters of the genetic drivers for severe COVID-19.” 

This is important in figuring out “why some people have had more severe symptoms of Covid-19 than others”.

Senior Author Professor Michael P Snyder of the University of Stanford led the work, which was published today in the journal Cell Systems, in partnership with genetics teacher Dr Sai Zhang and neuroscientist Dr Cooper-Knock, who is presently a Stanford visiting scholar.

The study

To unravel the genetics of severe COVID-19, the researchers analyzed many big data sets. The first piece of data included genetic information from human lung tissue that was in excellent condition. The information was used to identify gene expression in 19 various types of lung cells, including epithelial cells, which line the respiratory system and are the body’s first line of defense against infection.

The COVID-19 Host Genetics Initiative, one of the largest genetic investigations of critically ill coronavirus patients, provided more information. The researchers sought for genetic hints in the data, such as DNA variations known as single nucleotide polymorphisms, that could suggest whether someone is at a higher risk of severe COVID-19. They looked at whether certain mutations were more common or less common in COVID-19 patients with advanced illness.

Patients who got severe COVID-19 had mutations that kept happening or were missing in a way that stood out. This suggested that these changes might be what made the infection so bad.

However, genetic alterations might be difficult to interpret on their own. Other data detailing which parts of the genome are critical for distinct cell types inside lung tissue helped the team better comprehend their findings. The researchers were able to establish which genes were malfunctioning and among which cell types by overlaying the mutations onto cell-specific genomes.

Genes that put you at risk

The researchers were also curious as to which cell types had defective gene expression. They discovered that severe COVID-19 is linked to a reduced response from two well-known immune cells, natural killer (NK) cells and T cells, using their machine learning technology. The most essential cells are NK cells and a subtype known as ‘CD56 bright.’

“NK cells, which humans are born with and are the body’s first line of defense against infection,” as explained by Dr. Cooper-Knock, “are known for their ability to destroy viruses and cancer cells”.

NK cells also aid in the production of cytokines, which are immune system proteins. Interferon-gamma, for example, is a crucial stimulator of immune cells. NK cells mount an immediate and coordinated response against viral infections by collaborating with interferon-gamma.

“NK cells are like the generals directing the war,” according to the author. “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.”

Professor Snyder compared COVID-19 risk genes to harmful versions of the BRCA genes that make some people more likely to get cancer.

“Our findings lay the foundation for a genetic test that can predict who is born with an increased risk for severe COVID-19,” Professor Snyder added.

“Imagine there are 1,000 changes in DNA linked to severe COVID-19. If you have 585 of these changes,” according to professor Snyder, “that might make you pretty susceptible, and you’d want to take all the necessary precautions.”

Dr. Cooper-Knock also mentioned that medications to reactivate sluggish NK cells have already been recommended as a treatment for various cancers. “The drugs bind to receptors on the NK cells and trigger them to have a more robust response,” he explained.

“Trials of NK cell infusions for severe COVID-19 are underway.”

Image Credit: Getty

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