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September 14, 2022

Are you a Covid-19 'superdodger'?

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    At this point in the pandemic, most people have been infected by the coronavirus at least once. However, some people may have genetic mutations that allow them to be "superdodgers" and avoid getting sick despite exposures to the virus, Michaeleen Doucleff writes for NPR's "Goats and Soda."

    Is it possible to avoid Covid-19 infection altogether?

    According to CDC data, most people in the United States have had Covid-19 at least once. However, even with so many infections, there are still reports of people who have never tested positive or had symptoms despite multiple exposures to the coronavirus.

    "We've heard countless anecdotes about nurses and health-care workers being exposed without any protection and remaining negative over and over again," said Jean-Laurent Casanova, a pediatrician who studies the genetics of viral resistance at Rockefeller University. "Or people share a household with someone who's been coughing for a couple of weeks, and one person stays negative."

    Currently, Casanova and his colleagues are researching potential genes that could prevent someone's cells from being infected by the coronavirus, similarly to how people who have a CCR5 gene mutation are completely resistant to HIV.

    "It's kind of like the virus is knocking at the door, but nobody's opening the door," said Nathaniel Landau, a virologist at the NYU Grossman School of Medicine who helped identify the CCR5 mutation in the early 1990s. "The door is locked."

    "You can put as many virus particles as you want onto those cells, and they will not get infected," Landau said. "So in the case of resistance to HIV, the story was very clear."

    However, Landau said the way the coronavirus infects cell is different from HIV, and researchers have not yet been able to identify "an obvious and dramatic mutation" like CCR5 that would prevent people from getting infected by the coronavirus.

    Unlike HIV, which uses the CCR5 molecule to infect cells, the coronavirus uses the ACE2 receptor, which regulates blood pressure. Because the ACE2 receptor is necessary for survival, "[y]ou're not going to have many people walking around that don't have ACE2," Landau said.

    How a genetic mutation could stop Covid-19 symptoms before they begin

    Although researchers have not been able to identify a major gene mutation like CCR5 with the coronavirus, Landau said people have may have other genetic mutations that protect them from developing Covid-19 symptoms, if not from infection itself.

    For example, Jill Hollenbach and other researchers at the University of California, San Francisco (UCSF), analyzed DNA from more than 1,400 people who tested positive for Covid-19 but showed no symptoms and identified a mutation on the HLA gene.

    According to the researchers, this mutation increases a person's chance of having an asymptomatic Covid-19 infection by almost 10 times. People who have this mutation have T cells that can pre-emptively recognize and fight off the coronavirus before it can spread and cause symptoms to develop.

    "Your immune response and these T cells fire up much more quickly [than in a person without the HLA mutation]," Hollenbach said. "So for lack of a better term, you basically nuke the infection before you even start to have symptoms."

    For this mutation to work, an individual must have had an infection with another coronavirus, such as a common cold coronavirus, first. In general, everyone can generate T cells to fight back common colds, but people who have the HLA mutation can also generate T cells to combat SARS-CoV-2.

    "It's definitely luck" if you have the mutation, Hollenbach said. "But, you know, this mutation is quite common. We estimate that maybe 1 in 10 people have it. And in people who are asymptomatic, that rises to 1 in 5."

    Currently, the research into the HLA mutation from Hollenbach and her colleagues at UCSF is still preliminary, and they are still looking to other potential genes that could help people quickly neutralize a coronavirus infection.

    "These findings are like hot off the presses," Hollenbach said. "We haven't published them yet. It's all stuff that's been happening this summer." (Doucleff, "Goats and Soda," NPR, 9/12)

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