Most people in the U.S. have had COVID-19 at least once — likely more than 70% of the country, White House COVID-19 Response Coordinator Ashish Jha said Thursday, citing data from the Centers for Disease Control and Prevention. and Disease Prevention.
Many of them have been infected several times. In a preliminary study looking at 257,000 US veterans who had contracted COVID-19 at least once, 12% had a reinfection by April and about 1% had been infected three times or more.
This raises an obvious question: What is keeping that shrinking minority of people from getting sick?
Disease experts are looking for several 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 the reasons people may be better equipped to fend off COVID-19, they warn that some of these defenses may not hold up against omicron’s latest version, BA.5, which it is extremely good at spreading and dodging. protection from vaccines.
“It really takes two to tango,” said Neville Sanjana, a bioengineer at the Genome Center in New York. “If you think about having an infection and any of the bad things that happen after that, it’s really the product of two different organisms: the virus and the human.”
Genetics may lower the risk of COVID-19
In 2020, New York University researchers identified a host of genes 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 ACE2, which allows the virus to enter cells, can reduce a person’s likelihood of becoming infected.
Sanjana, who conducted that research, estimated that about 100 to 500 genes may influence susceptibility to COVID-19 in areas such as the lungs or nasal cavity.
Genetics are “likely to be a big contributor” to protection from 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 a coronavirus infection. In a study of 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 COVID-19 hospitalization.
Increasing gene expression, then, should have the opposite effect—reducing the risk of severe disease—although it would not necessarily prevent infection.
“It’s very natural to get infected after being exposed. There is no magic bullet for this. But once you get infected, how you respond to that infection is what will be affected by your genetic variants,” said Ludmila Prokunina-Olsson, the study’s principal investigator and head of the Translational Genomics Laboratory at the National Cancer Institute.
However, Benjamin tenOever, a professor of microbiology at NYU Grossman School of Medicine who helped conduct the 2020 research, said it would be difficult for scientists to pinpoint a specific gene responsible for preventing a COVID infection. -19.
“While there may still be some genetics out there that make people completely resistant, they will be incredibly difficult to find,” tenOever said. “People have already been searching intensively for two years with no actual results.”
T cells can remember past encounters with the coronavirus
In addition to this new coronavirus, SARS-CoV-2, four other coronaviruses commonly infect humans, usually causing mild to moderate upper respiratory illnesses like the common cold.
A recent study suggested that repeated exposure or occasional infections from these common cold coronaviruses may confer some protection from 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 past exposure to other coronaviruses. So when a person who has been infected with a common cold coronavirus is later exposed to SARS-CoV-2, they may not get as sick.
But this memory T cell may not completely prevent COVID-19.
“While neutralizing antibodies are key to preventing an infection, T cells are key to terminating an infection and modulating the severity of the infection,” said Alessandro Sette, study author and professor at the La Jolla Institute for 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-19. But researchers aren’t yet sure if that’s what’s happening.
“It’s possible that, despite testing negative, it was a very failed, transient infection that went undetected,” Sette said.
At the very least, he said, T cells from past COVID-19 infections or vaccines should continue to provide protection against coronavirus variants, including BA.5.
Allergies may result in little additional protection
Although asthma was considered a potential risk factor for severe COVID-19 earlier in the pandemic, more recent studies suggest that low-grade inflammation from conditions such as allergies or asthma may have a protective benefit.
“You’ll hear these stories about some individuals who get sick and have full-blown symptoms of COVID and have slept next to their partner for a whole week during that period 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 in any way has a higher-than-normal inflammatory response going on in their lungs,” tenOever said.
A May study found that having a food allergy halved the risk of a coronavirus infection in about 1,400 American households. Asthma did not lower the risk of infection in the people in the study, but neither did it increase it.
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 you’ll just be less likely to get infected,” said Tina Hartert, a professor of medicine and pediatrics at the University School of Medicine. Vanderbilt, who co-directed it. research.
The study took place from May 2020 to February 2021, before the omicron variant appeared. But Hartert said BA.5 likely won’t eliminate cross-protection from allergies.
“If something like allergic inflammation is protective, I think that would be true for all variants,” Hartert said. “The extent to which he can be defensive can certainly change.”
Avoiding infection is more challenging with BA.5
For many people, the first explanation that comes to mind when thinking about avoiding COVID-19 is one’s personal level of care. NYU’s TenOever believes that individual behavior, 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-19, 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 known that COVID-19 was easier to avoid before the omicron, when a small percentage of infected people were responsible for most of the spread of the virus. A 2020 study, for example, found that 10% to 20% of infected people accounted for 80% of transmissions.
But the omicron and its subvariants have made every social interaction more dangerous for everyone involved.
“It’s probably much more of a level playing field with the omicron variants than it ever was for the previous variants,” tenOever said.
BA.5, in particular, has increased the chances that people who have so far avoided COVID-19 will get sick. President Joe Biden is a prime example: He tested positive for the first time this week.
But even so, Jha said Thursday at a news conference, “I don’t believe every American will be infected.”
This article originally appeared on NBC News.