It’s a story many have heard before. COVID-19 enters a household whether through a spouse, parent, sibling or caretaker – but despite extensive exposure, not everyone gets sick.
And it could be a more common occurrence than some think. The U.S. reports more than 80 million coronavirus cases, which is likely a significant undercount. Experts estimate that more than half of Americans have yet to get the coronavirus.
Given that at its peak in January, more than 800,000 people were getting COVID-19 on average each day, questions have swirled about how some people have managed to escape the coronavirus so far.
Of course, some people have been more careful than others. Mitigation measures like social distancing and mask wearing are proven to work, as well as getting vaccinated.
“Things like working from home and avoiding crowds will minimize a person’s number of encounters with people who might have an active infection, and then things like being vaccinated and wearing a well-fitting mask can decrease the risk of acquiring infection if someone does, in fact, come into contact with someone who has an actively infectious virus,” says Kimberly Powers, an epidemiologist at the University of North Carolina at Chapel Hill Gillings School of Public Health.
There’s also people who have actually had COVID-19 without knowing it, whether the case was asymptomatic or so mild it didn’t prompt testing.
“Especially early on, there were a lot of asymptomatic cases,” says Robert Murphy, the executive director of the Havey Institute for Global Health at Northwestern University Feinberg School of Medicine. “They either had very minor symptoms that they didn’t expect anything funny or anything more severe, or they had no symptoms at all.”
Cartoons on the Coronavirus
But then there are others who have had repeated exposure to the virus who never contracted it, and researchers want to know why.
“We all know these examples of people you would expect to contract infection because they were in the midst of heavily infected people with very severe symptoms for a prolonged time without having access to face masks and other protective measures but who, for some reason, just simply did not get infected,” says András Spaan of the Rockefeller University.
What Could Be Behind ‘Never COVID’
The cohort of people who haven’t gotten the coronavirus despite exposure is puzzling researchers.
Many studies are underway to test different hypotheses about why some people just haven’t gotten the coronavirus. Could they have better immune systems or maybe a genetic difference that protects them from COVID-19?
One study published in January suggested that infection from the common cold and other coronaviruses could provide protection against COVID-19.
“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.
How Genetics Might Come Into Play
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.”
He points out that some people can’t get infected with HIV, malaria or certain noroviruses.
Although the study will examine people who were unvaccinated during coronavirus exposure, Spaan strongly encourages people to get the shots.
“Vaccination is the one and only effective manner to prevent you from getting a very severe disease,” Spaan says.
What Should People Who Haven’t Gotten COVID-19 Do?
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.
“I would suggest that continuing to stick with as many mitigation measures as they can tolerate would be to their benefit,” says Powers.
Ultimately, a lot of the exposure encounters just come down to chance, she says.
“Individual behaviors and decisions play a big role, but there’s a huge role of chance as well – where you go to the grocery store sparingly, but the last time you went it just so happened that someone with an active infection coughed in your direction,” Powers says.
And just because a person has made it to this point in the pandemic without infection doesn’t mean they won’t get COVID-19 in the future. Powers encourages those who do contract the virus not to feel guilty about it.
“I do worry about some people who have not become infected yet, that it may be sort of extra damaging to their psyche, and I would hate to see that,” Powers says.