Scientists are focusing on why some people continue to avoid Covid. BA.5 could end this chance.

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

Many have been infected multiple times. In a preprint study of 257,000 US veterans who had caught Covid at least once, 12% had reinfection in April and about 1% had been infected three or more times.

This raises an obvious question: what prevents this minority of people from getting sick?

Disease experts focus on a few predictors 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 can better avoid Covid, they warn that some of those defenses may not stand up to omicron’s latest version, BA.5, which is remarkably effective at spreading and escape vaccine protection. .

“It really takes two to tango,” said Neville Sanjana, a bioengineer at the New York Genome Center. “If you think you have an infection and everything that happens after that, it’s really the product of two different organisms: the virus and the human.”

Genetics could lower Covid risk

In 2020, NYU researchers identified a multitude of genes that could impact a person’s susceptibility to coronavirus. In particular, they found that inhibiting certain genes that code for a receptor called ACE-2, which allows the virus to enter cells, could reduce a person’s risk of infection.

Sanjana, who conducted this research, estimated that around 100 to 500 genes could influence susceptibility to Covid-19 in sites like the lungs or nasal cavity.

Genetics is “likely to be a big contributor” to protection against Covid-19, he said. “I would never say it’s the only contributor.”

In July, researchers identified a common genetic factor that may influence the severity of coronavirus infection. In a study in more than 3,000 people, two genetic variations decreased the 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 for Covid-19.

Increasing gene expression should therefore have the opposite effect – reducing the risk of severe disease – although it would not necessarily prevent infection.

“It’s very natural to get infected once you’re exposed. There’s no magic formula for that. But after you get infected, how you’re going to react to that infection is what’s going to be affected. by your genetic variants,” said Ludmila Prokunina-Olsson, principal investigator of the study and head of the Translational Genomics Laboratory at the National Cancer Institute.

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

“While there may still be genes that make people completely resistant, they will be incredibly hard to find,” tenOever said. “People have already searched intensely for two years without any real results.”

T cells could remember past encounters with the coronavirus

Besides this new coronavirus, SARS-CoV-2, four other coronaviruses commonly infect people, usually causing mild to moderate upper respiratory illnesses like the common cold.

A recent study suggested that repeated exposure or occasional infections with these cold coronaviruses may confer some protection against SARS-CoV-2.

Researchers have found that T cells, a type of white blood cell that recognizes and fights invaders, appear to recognize SARS-CoV-2 based on past exposure to other coronaviruses. So when someone who has been infected with a cold coronavirus is then exposed to SARS-CoV-2, they may not get as sick.

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

“While neutralizing antibodies are key to preventing an infection, T cells are key to ending an infection and modulating the severity of the infection,” said Alessandro Sette, study author and professor at the Institute. La Jolla of Immunology.

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

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

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

Allergies can lead to a little extra protection

Although asthma was considered a potential risk factor for severe Covid at the start of the pandemic, more recent research suggests that low-grade inflammation due to conditions such as allergies or asthma may have a protective effect.

“You will hear these stories of people getting sick and showing full symptoms of Covid, and having slept next to their partner for an entire week during this time without giving it to them. People think they must have some genetic resistance to it, [but] a lot of that could be if the partner next to them somehow has a higher than normal inflammatory response in their lungs,” tenOever said.

A can study found that having a food allergy halved the risk of coronavirus infection in nearly 1,400 US households. Asthma did not reduce people’s risk of infection in the study, but it did not increase it either.

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

“Because there are fewer receptors, you’ll either have a much lower grade infection or just be less likely to get infected,” said Tina Hartert, a professor of medicine and pediatrics at Vanderbilt University School of Medicine who co-directed this research. .

The study ran from May 2020 to February 2021, before the omicron variant emerged. But Hartert said BA.5 is unlikely to eliminate allergy cross-protection.

“If something like allergic inflammation is protective, I think that would be true for all variants,” Hartert said. “The degree to which that might be protective could certainly differ.”

Avoiding infection is more difficult with BA.5

For many, the first explanation that comes to mind when thinking about avoiding Covid is their personal level of caution. tenOever believes that individual behavior, more than genetics or T cells, is the key factor. He and his family in New York are among those who have never had Covid, which he attributes to precautions like staying home and wearing masks.

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

It is now common knowledge that Covid was easier to avoid before omicron, when a small percentage of infected people were responsible for the majority of the spread of the virus. A study 2020for example, found that 10-20% of those infected accounted for 80% of transmission.

But omicron and its subvariants made any social interaction more risky for everyone involved.

“It’s probably a much more even playing field with omicron variants than it ever was with previous variants,” tenOever said.

BA.5 in particular has increased the chances of people who have avoided Covid so far getting sick. President Joe Biden is a prime example: he tested positive for the first time this week.

But even so, Jha said Thursday, “I don’t believe all Americans will get infected.”

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