Life-Threatening COVID-19 Cases May Be Linked to 5 Key Genes | Virus World | Scoop.it
From www.businessinsider.com - December 12, 2020 9:58 PM
  • Five genes seem to be associated with life-threatening cases of COVID-19, a new study found.
  • The finding offers a potential explanation for why some patients get severely sick while others don't
  • Two of these genes are linked to the innate immune response, while three are tied to inflammation and lung damage.
  • The study offers a direction for more research into certain potential COVID-19 treatments.

 

A growing body of research is highlighting a select set of genes that may explain why some people develop more severe COVID-19 cases than others. Certain genes, for instance, instruct the body to make more ACE2 receptors, which the coronavirus uses to invade our cells. Studies show that people whose bodies naturally code for more of these receptors could be at higher risk of severe infection. On Friday, researchers at the University of Edinburgh announced that they'd identified five genes that may be associated with life-threatening cases of COVID-19. The genes are, perhaps unsurprisingly, associated with a weaker innate immune response and more aggressive inflammation. The new study compared more than 2,200 coronavirus patients in UK intensive-care units to patients of similar ancestry who hadn't tested positive for COVID-19.  The critically ill COVID-19 patients were found to have a lower expression of IFNAR2, a gene that helps code for proteins called interferons. These act as an emergency flare to warn the immune system of an intruder. The patients also displayed a variation in a cluster of genes called OAS, which normally helps prevent a virus from replicating.  What's more, the critically ill patients had higher expressions of the genes TYK2 and CCR2, which can drive inflammation and potentially lead to lung injury. And they displayed a variation in the gene DPP9, which scientists have linked to pulmonary fibrosis (damaged or scarred lung tissue).

 

A weak immune system is at risk of collapse

 

Typically, when our immune system senses a foreign invader, it dispatches white blood cells to destroy the threat. But in some patients, that innate immune response isn't strong enough to vanquish the coronavirus right away. This can trigger aggressive inflammation that damages healthy tissue or leads to organ failure. Dr. Panagis Galiatsatos, a pulmonary physician at Johns Hopkins Bayview Medical Center, compared that process to an earthquake — generally, it's the falling buildings that kill someone, not the quake itself. "Your infection is a rattling of your immune system," he previously told Business Insider. "If your immune system is just not well structured, it's just going to collapse." That means genetic signals that inhibit the body's natural defenses or encourage inflammation might set off a chain reaction that ultimately leads to critical respiratory failure. Other factors, including age and underlying health conditions, play a role in severe COVID-19 cases as well.

 

Implications for COVID-19 treatments

 

In unlocking some of the mysteries surrounding severe COVID-19, the Edinburgh researchers also found clues about how to treat patients. "Our results immediately highlight which drugs should be at the top of the list for clinical testing," Kenneth Baillie, an academic consultant in critical-care medicine who co-led the research, told Reuters.   Drugs that boost the expression of INFAR2, for instance, might help patients fight the virus before it wreaks havoc in the body. One potential treatment, a multiple sclerosis drug called Rebif, is attempting a similar approach by giving patients a boost of interferon. Merck, the company behind the drug, hopes the therapy might prevent the coronavirus from replicating. The Edinburgh study also suggests that drugs targeting inflammation could play a key role in halting the disease's progression. In particular, the researchers point to a class of anti-inflammatory drugs called Janus kinase (JAK) inhibitors, which are already used to treat rheumatoid arthritis.  One such arthritis drug, Eli Lilly's baricitinib, was recently authorized by the FDA for use in combination with remdesivir....

 

Cited Research Published in Nature (Dec. 11, 2020):

https://doi.org/10.1038/s41586-020-03065-y