Most people in the US have had Covid-19 at least once, probably more than 70% of the country, Ashish Jha, White House COVID-19 response coordinator, said on Thursday, citing data from the Centers for Disease Control and Prevention.
Many have been infected multiple times. in a preprint study looking at 257,000 US 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 prevents that shrinking minority of people from getting sick?
Disease experts focus on some 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 may be better equipped to ward off covid, they warn that some of these defenses may not hold up to the latest version of omicron, BA.5, which is remarkably good at spreading and evade vaccine protection. .
“It really does take 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 actually caused by two different organisms: the virus and the human.”
Genetics could decrease the risk of Covid
In 2020, researchers at New York University identified a multitude of genes that could 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, could reduce a person’s likelihood of infection.
Sanjana, who conducted that research, estimated that between 100 and 500 genes could influence susceptibility to covid-19 in sites such as the lungs or the nasal cavity.
Genetics are likely to “contribute a great deal” to protection against Covid-19, he said. “I would never say that it is the only contributor.”
In July, researchers identified a common genetic factor that could influence the severity of a coronavirus infection. in a to study In more than 3,000 people, two genetic variations reduced the expression of a gene called OAS1, which is part of the innate immune response to viral infections. That was associated with a higher risk of hospitalization for Covid-19.
Therefore, increasing the expression of the gene should have the opposite effect, reducing the risk of serious disease, although it would not necessarily prevent infection completely.
“It’s very natural to get infected once you’re exposed. There’s no magic wand for that. But after you get infected, how you’re going to respond to this infection, that’s going to be affected by your genetic variants,” he 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 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 particular gene responsible for preventing a Covid infection.
“While there may still be some genetics that make people completely resistant, they’re going to be incredibly hard to find,” tenOever said. “People have already been searching intensively for two years with no real results.”
T cells could remember past encounters with coronavirus
In addition to this new coronavirus, SARS-CoV-2, four other coronaviruses commonly infect people and typically cause mild to moderate upper respiratory illness, such as the common cold.
A recent study suggested that repeated exposure to or occasional infections with these common cold coronaviruses may confer some protection against SARS-CoV-2.
The researchers found that T cells, a type of white blood cell that recognizes and fight off invaders, appear to recognize SARS-CoV-2 based on previous exposure to other coronaviruses. So when a person who has been infected with a common cold coronavirus is later exposed to SARS-CoV-2, he may not get as sick.
But that T-cell memory probably can’t prevent covid entirely.
“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 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 aren’t yet sure if that’s what’s happening.
“It is possible that despite being negative on the test, it was a very abortive transient infection that went undetected,” Sette said.
At a minimum, he said, T cells from previous Covid infections or vaccines should continue to offer some protection against variants of the coronavirus, including BA.5.
Allergies may result in a little extra protection.
Although asthma was considered a potential risk factor for severe Covid early 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 people who got sick and had full symptoms of covid, and slept next to their partner for a whole week during that period without giving it to them. People think you must have some genetic resistance. it, [but] a big part of that could be if the partner next to you has a higher-than-normal inflammatory response in their lungs,” tenOever said.
A can study found that having a food allergy cut the risk of coronavirus infection in half among nearly 1,400 American households. Asthma did not reduce the risk of infection for the people 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 airway cells, making it harder for the virus to enter.
“Because there are fewer receptors, you’re going to have a much lower-grade infection or be less likely to even get infected,” said Tina Hartert, a professor of medicine and pediatrics at Vanderbilt University School of Medicine, who co-led that research. .
The study was carried out from May 2020 to February 2021, before the omicron variant emerged. But Hartert said BA.5 probably wouldn’t remove the cross-protection against allergies.
“If something like allergic inflammation is protective, I think that would be true for all variants,” Hartert said. “The degree to which it could be protective could certainly differ.”
Avoiding infection is more challenging with BA.5
For many, the first explanation that comes to mind when thinking about avoiding Covid is a personal level of precaution. NYU’s TenOever believes that individual behavior, rather 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 like staying home and wearing masks.
“I don’t believe 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 omicron, when a small percentage of infected people were responsible for most of the spread of the virus. A study 2020for example, it found that 10% to 20% of infected people accounted for 80% of transmissions.
But omicron and its subvariants have made any social interaction riskier for everyone involved.
“It’s probably a much more level playing field with omicron variants than previous variants,” tenOever said.
BA.5, in particular, has increased the odds that people who have avoided covid so far will get sick. President Joe Biden is a prime example: he tested positive for the first time this week.
But still, Jha said Thursday at a news conference, “I don’t think all Americans will get infected.