Three years into the pandemic, a select group of people have achieved something some once thought impossible: They have never tested positive for Covid. Researchers around the globe are trying to find out why these individuals have not been affected by Covid despite being exposed repeatedly.
Were they born with a form of super immunity? Is there a reason they are able to escape infection like Houdini?
“Mostly luck,” said Adam Zimmerman, 40, of Rockville, Maryland, laughing. Neither Zimmerman nor his wife and children have tested positive for Covid. Zimmerman stated that he and his wife took all the precautions possible to prevent infection. He also noted that his family has received their vaccinations. “So far, so good.”
Since March 11, 2020, more than 676 million people around the world have had a confirmed infection. Nearly 60 percent of the U.S. population has had Covid, according to the Centers for Disease Control and Prevention. Many more cases could have been missed because people didn’t experience symptoms.
Even though millions of people have been vaccinated and followed precautions similar to the Zimmermans, they still got sick from Covid, either because of breakthrough infections or waning immunity. Scientists believe that it’s possible for some people to have been immune from the Covid virus since they were equipped with biological armor that protects them against infection.
Now they want to unravel the mysteries hidden in the immune systems of true “Covid dodgers.”
Is it possible to be immune to Covid?
“We are searching for rare genetic variants that make people resistant to SARS-CoV-2 infection,” said Dr. Jean-Laurant Casanova, a pediatric immunologist, geneticist and professor at Rockefeller University in New York. “If we were to discover them, the impact would be significant.”
Casanova is working with an international team of scientists in a project called the Covid Human Genetic Effort.
“There’s a couple of genes that have our attention,” said Dr. Andras Spaan, a clinical microbiologist on the team. “One of them, of course, is ACE2,” a gene known to help Covid infiltrate the body.
In theory, some people may have DNA that does the opposite: preventing ACE2 or other genes from allowing a Covid invasion. If researchers can zero in on a protective genetic factor, it’s possible that they could develop drugs to prevent infection and further spread of the virus.
The team has recruited approximately 1,000 people worldwide, using saliva samples to study volunteers’ DNA.
Not surprisingly, many of the study’s early recruits eventually tested positive for the virus, especially after the highly contagious omicron took hold in 2022.
Some never became infected, Spaan said, “even with omicron and repeated, intense exposure.”
Rachel Zucker-Wong, 29, of San Francisco has a similar story. She recalled a time in September 2021, as the “hypertransmissible” delta variant was driving cases nationwide, when she sat next to a man at a wedding dinner who she later learned had Covid. We were right beside him. We were hugging him. “We were all toasting,” Zucker Wong stated. “And I never got it.”
In fact, she has never tested positive, despite her husband getting Covid and her repeated exposure to the virus as a nursing school student.
Brian Peach was a nurse at the Orlando Regional Medical Center’s Covid ICU in Florida during the early days of the pandemic. This was before Covid vaccines became widely available.
” We were always in patient’s rooms, administering medications and supporting blood pressure,” stated Peach. He is also assistant professor at the College of Nursing, University of Central Florida. “We’d be in there suctioning their breathing tubes and doing regular oral care to prevent ventilator-associated pneumonias.”
He’s never tested positive, and is fascinated by the thought of having some kind of protective DNA.
“I’d love to know if I have something in particular that’s helped me, other than the vaccines,” Peach said.
It is not uncommon for people to have genes that protect them against other viruses such as HIV. That discovery has led to a handful of cases in which people living with HIV have possibly been cured with a stem cell transplant from naturally resistant donors.
Early in the pandemic scientists in the United Kingdom intentionally tried to infect people to see what would happen.
The Human Challenge Programme was small, including just 36 healthy young men and women. The virus was injected into the noses of participants by researchers at Imperial College London. They then waited. (Participants were all carefully monitored for any complications, but none occurred. )
3 years and counting: The latest Covid news
Half of the participants became infected, experiencing mild symptoms. The other half, despite literally having Covid placed into their nasal cavity, remained infection-free.
As the pandemic progressed however, many participants developed the infection. This was according to Peter Openshaw who is a professor in experimental medicine at Imperial College London and led the research.
This means that any Covid-born immunity was very unlikely.
” We don’t believe that anything inherently prevented them being infected,” Openshaw stated. The participants were protected by “probably an unplanned event.”
Perhaps “the very low concentration of the virus that was given got caught up in a lump of mucus and was expelled rather than managing to penetrate and cause infection,” Openshaw said.
Exposed to Covid, but no symptoms
As the search continues for an elusive immunity gene, asymptomatic infections may be the real story. This means that people don’t know they have Covid, because the virus is stopped from making them sick.
One study conducted early in the pandemic, when routine testing was common, suggested that more than 40% of cases could be asymptomatic. The CDC stopped tracking the number of asymptomatic patients when routine testing was less frequent.
Openshaw finds asymptomatic cases “absolutely fascinating.”
“What is it that clears the virus before it gets a foothold?,” he asked. That’s what Jill Hollenbach (a professor at the University of California San Francisco’s department of neurology and the Department of Epidemiology and Biostatistics) is trying to find.
“Some people don’t show any symptoms.” Hollenbach stated. “There’s something happening at a really fundamental level in the immune response that is helping those people to just completely wipe out this infection.”
Hollenbach’s lab is focusing on human leukocyte antigen, or HLA. This molecule is found on all cells of the body and acts as a vigilant guard dog.
HLA constantly shows the immune system what it finds near cells. Usually, they’re harmless bits that are supposed to be in the body. Immune systems are generally unfazed by this.
Sometimes HLA holds up something that the immune system doesn’t recognize, such as a virus like Covid. That’s when it is supposed to launch an attack.
HLA’s capabilities vary from one person to another, so Hollenbach had to determine which HLA version is most adept in triggering the immune system to eliminate the Covid.
She turned to the National Donor Program, which includes roughly 13 million people — all with neatly logged HLA types.
HLA genes are the same that must be matched in people seeing an organ or stem cell transplant.
Hollenbach’s team then followed about 30,000 people from that registry from the beginning of the pandemic until April 2021, when the vaccines became widely available.
More than 13,000 ultimately tested positive. Ten percent of patients were completely symptomatic.
“We were pretty stringent in our definition of asymptomatic. You don’t even have a scratchy throat,” Hollenbach said.
Strong immunity, a common genetic thread
Her team discovered a common genetic thread: a gene called HLA-B*15:01. Hollenbach discovered that people with this HLA variant were twice as likely to get an asymptomatic disease. That protection was increased by more than eight times if a person had two copies of the gene.
Her research was published on a preprint server, and is currently under consideration with a peer-reviewed journal, Hollenbach said.
People who have asymptomatic infections may be useful to study in other ways, as well. Professor of immunobiology at Yale University Akiko Iwasaki suggests that people who have never been infected by Covid might not be again.
“That would be important because that’s really what we want to achieve in the population,” Iwasaki said.
People who have been infected, but don’t show any symptoms, may be able to develop a strong mucosal immune system.
This is because when people inhale bits of virus in their noses and mouths, an army immune cells rapidly forms in their bodies. These cells are alert to the possibility of infection and will keep an eye out for it if they’re exposed again.
“That could indicate that these people have developed very robust local immune responses that prevent future infections,” Iwasaki said. The future research with saliva samples could reveal whether these mucosal immune cell may retain the memories of Covid.
Hollenbach said that it appears people whose immune systems include the form of the HLA gene also have a fantastic ability to remember prior infections, jumping into action immediately when it finds something menacing that’s been there before.
Hollenbach believes this is why kids have generally been spared the worst outcomes of Covid. Their little bodies are already extremely familiar with respiratory viruses.
“They basically spend years just completely snotty from ages 1 to 7,” she said. “They’re experiencing these seasonal coronaviruses at a really rapid clip, passing them around all of the time.”
The idea is intriguing to other experts.
“There’s a lot of work going on to try to see whether cross-reactive immunity stimulated by common cold coronaviruses could be a factor that causes differences in the way in which people respond to Covid,” Openshaw said. It may explain why Sue Nowatzke (a semi-retired nurse from Ames in Iowa) has been Covid-free.
“Ever since I was a kid, I easily caught any kind of respiratory crud,” said Nowatzke, 64. “And when I worked in the hospital, I was always sick.”
The last time Nowatzke remembers being ill was in December 2019. Since then, “I can’t even remember a sniffle,” she said.
She has never tested positive, despite repeated exposures to Covid while working as a nurse in June 2021.
Her husband, Duane, 68, has also never tested positive, but they aren’t sure it’s because of some innate ability to fend off Covid. They say they’ve relied heavily on masking and staying up to date on vaccination.
“They come up with a shot, we get it,” Duane Nowatzke said.
Is Covid infection inevitable?
As scientists search for genetic factors that may render a lucky few immune to Covid, experts encourage caution.
“You never want to be like, ‘I haven’t gotten Covid, therefore I am invincible,'” said Dr. Michael Angarone, an infectious diseases specialist at Northwestern Medicine.
Some believe it’s inevitable that the entire population will become infected sooner or later. Although masking and vaccinations can be effective, they are not foolproof.
“There’s very few people left that I know of who have not had the infection,” said Angarone. “Even the people I know who were washing their groceries and whatnot ended up getting infected.”
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