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Scientists investigate why some people continue to avoid Covid. BA.5 could end that luck.

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Most people in the US have had Covid-19 at least once – probably more than 70% of the country, White House Covid-19 response coordinator Ashish Jha said on Thursday, citing data from the Centers for Disease Control and Prevention.

Many have been infected several times. In a pre-print In a survey of 257,000 U.S. veterans who had contracted Covid at least once, 12% had a reinfection in April, and about 1% had been infected three or more times.

This raises an obvious question: What’s stopping that dwindling minority of people from getting sick?

Disease experts focus on a few predictive factors beyond individual behavior, including genetics, T-cell immunity, and the effects of inflammatory conditions such as allergies and asthma.

But even as experts learn more about why people should avoid Covid, they warn that some of these defenses may not be up to the task of the latest version of omicron, BA.5, which is remarkably good at spreading and dodging. vaccine protection.

“It really takes two for the tango,” said Neville Sanjana, a bioengineer at the New York Genome Center. “If you think about infection and all the bad things that happen after that, it’s really a product of two different organisms: the virus and the human.”

Genetics can reduce the risk of Covid

In 2020, NYU Researchers a multitude of genes identified that can affect a person’s susceptibility to the coronavirus. In particular, they found that inhibiting certain genes that code for a receptor known as ACE-2, which allows the virus to enter cells, can reduce a person’s chance of infection.

Sanjana, who conducted that study, estimated that about 100 to 500 genes could influence susceptibility to Covid-19 in places like the lungs or nasal cavity.

Genetics will “probably go a long way” in protecting against Covid-19, he said. “I would never say it’s the only contribution.”

In July, researchers identified a common genetic factor that could influence the severity of a coronavirus infection. In a study of more than 3,000 people, two genetic variations reduced expression of a gene called OAS1, which is part of the innate immune response to viral infections. This was associated with an increased risk of hospitalization due to Covid-19.

So increasing the expression of the gene should have the opposite effect – reducing the risk of serious disease – although it wouldn’t necessarily prevent infection altogether.

“It’s very natural to get infected once you’re exposed. There’s no panacea for that. But after you get infected, how you’re going to respond to this infection will be influenced by your genetic variants,” said Ludmila Prokunina- Olsson, the study’s principal investigator and chief of the National Cancer Institute’s Laboratory of Translational Genomics.

Still, Benjamin tenOever, a microbiology professor at NYU Grossman School of Medicine who helped conduct the 2020 study, said it will be difficult for scientists to pinpoint a particular gene responsible for preventing a disease. Covid infection.

“While there are certainly still some genetics that make people completely resistant, they’re going to be incredibly hard to find,” tenOever said. “People have been searching intensively for two years without real results.”

T cells can remember previous encounters with the coronavirus

Aside from this novel coronavirus, SARS-CoV-2, four other coronaviruses commonly infect humans, typically causing mild to moderate upper respiratory illnesses, such as the common cold.

A recent research suggested that repeated exposure or occasional infections of these common cold coronaviruses may provide some protection against SARS-CoV-2.

The researchers found that T cells, a type of white blood cell that recognizes and fights invaders, appear to recognize SARS-CoV-2 based on previous exposure to other coronaviruses. So when a person infected with a cold coronavirus is later exposed to SARS-CoV-2, they may not get as sick.

But that T-cell memory probably can’t prevent Covid altogether.

“While neutralizing antibodies are key to preventing infection, T cells are key to ending infection and modulating infection severity,” said Alessandro Sette, the study’s author and a professor. at the La Jolla Institute for Immunology.

Sette said it’s possible that some people’s T cells clear up the virus so quickly that the person never tests positive for Covid. But researchers aren’t sure yet if that’s what’s happening.

“It’s possible that despite it being negative on the test, it was a very botched transient infection that went undetected,” Sette said.

At the very least, he said, T cells from previous Covid infections or vaccines should continue to provide some protection against coronavirus variants, including BA.5.

Allergies can result in a little extra protection

While asthma was considered a potential risk factor for severe Covid earlier in the pandemic, more recent research suggests that low-grade inflammation from conditions such as allergies or asthma may have a protective benefit.

“You will hear these stories about some individuals who get sick and have full symptoms of Covid, and have slept next to their partner for a whole week without giving it to them. People think they must have some genetic resistance to it.” , [but] a big part of that could be if the partner next to them has a higher-than-normal inflammatory response in their lungs in some way,” tenOever said.

A allowed to study found that having a food allergy halved the risk of coronavirus infection among nearly 1,400 U.S. households. Asthma didn’t reduce the risk of infection for people in the study, but it didn’t increase it either.

One theory, the researchers say, is that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it more difficult for the virus to enter.

“Because there are fewer receptors, you either have a much lower infection rate or you’re just less likely to even get infected,” said Tina Hartert, a professor of medicine and pediatrics at Vanderbilt University School of Medicine who co-led the study. that research.

The study took place from May 2020 to February 2021, before the ommicron variant emerged. But Hartert said BA.5 probably wouldn’t eliminate cross-protection from allergies.

“If something like allergic inflammation is protective, I think it goes for all variants,” Hartert said. “The degree to which it could be protective can certainly differ.”

Avoiding infection is more challenging with BA

For many, the first statement that comes to mind when thinking about avoiding Covid is one’s personal caution. tenOever believes that individual behaviour, more than genetics or T cells, is the key factor. He and his family in New York City are among those who have never had Covid, which he attributes to precautions such as staying home and wearing masks.

“I don’t think for a second that we have something special in our genetics that makes us resistant,” he said.

It is now common knowledge that Covid was easier to avoid before ommicron, when a small percentage of infected people were responsible for most of the virus’ spread. A 2020 studyfound, for example, that 10-20% of infected people were responsible for 80% of transmission.

But ommicron and its sub-variants have made any social interaction more risky for everyone involved.

“It’s probably much more of a level playing field with the omicron variants than ever for the earlier variants,” tenOever said.

BA.5, in particular, has increased the likelihood that people who have so far avoided Covid will get sick. President Joe Biden is a good example: he tested positive for the first time this week.

Still, Jha said on Thursday, “I don’t believe every American will get infected.”

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