Americans who haven’t had covid-19 are now officially in the minority. A study published this week from the US Centers for Disease Control and Prevention (CDC) found that 58% of randomly selected blood samples from adults contained antibodies indicating that they had previously been infected with the virus; among children, that rate was 75%.
What is different about that minority of people that hasn’t yet gotten infected? Stories abound of close calls, of situations where people are sure they could have (or should have) gotten sick, but somehow dodged infection. Not all the questions are answered yet, but the question of what distinguishes the never-covid cohort is a growing area of research even as the US moves “out of the full-blown” pandemic. Here are the possibilities that scientists are considering to explain why some people haven’t contracted the virus.
They behave differently
We’ve seen it play out time and time again—some people adhere more strictly to protocols known to reduce transmission of the virus, including wearing a mask and getting vaccinated. Some people avoid large public settings and may have even been doing so before the pandemic, says Nicholas Pullen, a biology professor at the University of Northern Colorado. Then again, that doesn’t tell the whole story; as Pullen himself notes: “Ironically, I happen to be one of those ‘never COVIDers’ and I teach in huge classrooms!”
They’ve trained their immune systems
The immune system, as any immunologist or allergist can tell you, is complicated. Though vaccination against covid-19 can make symptoms more mild for some people, it can prevent others from contracting the illness altogether.
Growing evidence suggests that there may be other ways that people are protected against the virus even without specific vaccines against it. Some could have previously been infected with other coronaviruses, which may allow their immune systems to remember and fight similarly shaped viruses. Another study suggests that strong defenses in the innate immune system, barriers and other processes that prevent pathogens from infecting a person’s body, may also prevent infection.
An innate immune system that’s already not functioning as well due to other medical conditions or lifestyle factors such as sleep or diet may put a person at higher risk of getting sick from a pathogen. There’s not single answer here yet, but initial studies are intriguing and may offer avenues for future treatments for covid-19 and other conditions.
They’re genetically different
In the past, studies have found interesting associations between certain genetic variants and people’s susceptibility to communicable diseases such as HIV, tuberculosis, and the flu. Naturally, researchers wondered if such a variant could exist for covid-19. One June 2021 study that was not peer reviewed found an association between a genetic variant and lower risk of contracting covid-19; another large-scale study, focused on couples in which one person got sick while the other didn’t, kicked off in Oct. 2021.
“My speculation is that something will be borne out there, because it has been well observed that resistance embedded in genetic variation is selected in pandemics,” Pullen says. But most experts suspect that even if they are able to identify such a variant with some certainty, it’s likely to be rare. For now, it’s best for those who haven’t gotten covid to assume they’re as susceptible as anyone else. Whatever the reasons some people haven’t yet gotten sick, the best defense remains staying up to date with vaccinations and avoiding contact with the virus.
“Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why,” study author Rhia Kundu said in a statement, using the scientific name for the coronavirus. “We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.”
The study, which examined 52 people who lived with someone who contracted the coronavirus, found that those who didn’t get infected had significantly higher levels of T cells from previous common cold coronavirus infections. T cells are part of the immune system and believed to protect the body from infection. “Our study provides the clearest evidence to date that T cells induced by common cold coronaviruses play a protective role against SARS-CoV-2 infection,” study author Ajit Lalvani said in a statement.
Researchers cautioned that the findings should not be relied upon as a protection strategy. “While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone,” Kundu said. “Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.” And the findings on the subject have been inconsistent, with other studies actually suggesting that previous infection with some coronaviruses have the opposite effect.
A major question that has come from the so-called ‘never COVID’ group is whether genetics plays a role in preventing infection. In fact, the question has spurred a team of international researchers to look for people who are genetically resistant to COVID-19 in the hopes that their findings could improve therapeutics. “What we are doing essentially is that we are testing the hypothesis that some people might not be able to get infected because of their genetic and inborn makeup, meaning that they might be genetically resistant to COVID,” says Spaan, who is a member of the COVID Human Genetic Effort.
The effort has sequenced genetic data from about 700 individuals so far, but enrollment is ongoing and researchers have received thousands of inquiries, according to Spaan. The study has several criteria, including laboratory test confirmation that the person has not had previous COVID-19 infection, intense exposure to the virus without access to personal protective equipment like masks and an unvaccinated status at the time of exposure, among others. So far, the group doesn’t know what the genetic difference could be – or if it even exists at all, though they believe it does.
“We do not know how frequent it is actually occurring,” Spaan says. “Is it like a super rare individual with a very, very rare mutation? Or is that something more common?” But the hypothesis is “embedded in human history,” according to Spaan. “COVID is not quite the first pandemic that we are dealing with,” Spaan says. “Humans have been exposed to viruses and other pathogens across time from the early beginning, and these infections have left an imprint on our genetic makeup.”
Those who haven’t gotten the coronavirus are “very much at risk,” says Murphy of Northwestern University. “I think every unvaccinated person is going to get it before this is over.” Experts stressed that research to determine why some people get COVID-19 while others don’t is still very much underway, and no one should rely on any of the hypotheses for protection. Instead, those who haven’t gotten the coronavirus should continue mitigation measures that have been proven to work, like vaccination and mask-wearing.
“You don’t ever want to have COVID,” Murphy says. “You just don’t know which people are going to get really sick from this and die or who’s going to get long COVID, which is hard to diagnose and difficult to treat and very real.” But with coronavirus cases on the rise and mitigation measures like mask mandates dropping left and right, it’s not an easy task.
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