NOVIDS: Do Some Have the Genes to Dodge COVID?

9 min read

March 16, 2023 -- As a field service representative for a slot machine company, Ryan Alexander, 37, of Louisville, KY, spends his working hours in casinos, covering a large territory including Norfolk, VA, Indianapolis, and Charlotte. Social distancing in the casinos is not the norm. Despite all this up-close contact with people, he said he is still COVID-free, 3 years into the pandemic. 

There was one nervous night when his temperature rose to 101 degrees and he figured the virus had caught up with him. “I took a test and was fine,” he said, relieved that the result was negative. The fever disappeared and he was back to normal soon. “Maybe it was just an exhausting day.” 

Alexander is one of those people who have managed — or at least think they have managed — to avoid getting COVID-19. 

He is, some say, a NOVID. While some scientists cringe at the term, it’s caught on to describe these virus super-dodgers. Online entrepreneurs offer NOVID-19 T-shirts, masks, and stickers, in case these super-healthy or super-lucky folks want to publicize their good luck.On Twitter, NOVIDs share stories of how they’ve done it.

How Many NOVIDs?

As of March 16, according to the CDC, almost 104 million cases of COVID — about one-third of the U.S. population — have been reported, but many cases are known to go unreported. About half of American adults surveyed said they have had COVID, according to a December report by the COVID States Project, a multi-university effort to supply pandemic data. 

As the numbers settle over time, though, it becomes clearer that some in the U.S. have apparently managed to avoid the virus.

While the exact number of people who have remained uninfected isn’t known with certainty, a review of comprehensive serologic data shows about 15% of Americans may not have gotten infected with COVID, Eric Topol, MD, editor-in-chief of Medscape (WebMD's sister site for medical professionals) wrote in his substack Ground Truths.

But some scientists bristle at the term NOVIDs. They prefer the term “resisters,” according to Elena Hsieh, MD, associate professor of pediatrics and immunology at the University of Colorado Anschutz School of Medicine in Aurora. Currently, she said, there is much more information on who is more susceptible to contracting severe COVID than who is resistant.

Hsieh is one of the regional coordinators for the COVID Human Genetic Effort, an international consortium of more than 250 researchers and doctors dedicated to discovering the genetic and immunological bases of the forms of SARS-CoV-2 infection. These researchers and others are looking for explanations for why some people get severe COVID while others seem resistant despite repeated exposure. 

Resistance Research

In determining explanations for resistance to infection, “the needle in the haystack that we are looking for is a change in the genetic code that would allow for you to avoid entry of the virus into the cell,” Hsieh said. “That is what being resistant to infection is.”

Part of the reason it’s so difficult to study resistance is defining a resister, she said. While many people consider themselves among that group because they’re been exposed multiple times -- even with close family members infected and sick, yet they still felt fine -- that doesn’t necessarily make them a resister, she said. 

Those people could have been infected but remained without symptoms. “Resistance means the virus was inside you, it was near your cell and it did not infect your cell,” Hsieh said.

“I don’t think we know a lot so far,” Hsieh said about resisters. “I do believe that just like there are genetic defects that make someone more susceptible, there are likely to be genetic defects that make somebody less susceptible.’’

“To identify genetic variants that are protective is a really challenging thing to do,” agreed Peter K. Gregersen, MD, professor of genetics at the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, NY. Gregersen is also a regional coordinator for the COVID Human Genetic Effort. 

He suspects the number found to be truly resistant to COVID — versus dodging it so far — is going to be very small or not found at all. 

“It may exist for COVID or it may not,” he said. Some people may simply have what he calls a robust immune response in the upper part of the throat, perhaps killing off the virus quickly as soon as it enters, so they don’t get a positive test. 

Genetic resistance has been found for other diseases, such as HIV. 

“For HIV, scientists have been able to identify a specific gene that codes for a protein that can prevent individuals from getting infected,” said Sabrina Assoumou, MD, MPH, professor of medicine at Boston University School of Medicine, who researches HIV. 

However, she said, “we haven’t yet found a similar gene or protein that can prevent people from getting infected with SARS-CoV-2.”

What has been found “is that some people might have a mutation in a gene that encodes for what's called human leukocyte antigen (HLA),” Assoumou said. HLA, a molecule found on the surface of most cells, has a crucial role in the immune response to foreign substances. “A mutation in HLA can make people less likely to have symptoms if they get infected. Individuals still get infected, but they are less likely to have symptoms.”

Other research has found that those with food allergies are also less likely to be infected. The researchers have speculated that the inflammation characteristic of allergic conditions may reduce levels of a protein, called the ACE2 receptor, on the surface of airway cells. The SARS-CoV-2 virus uses the receptor to enter the cells, so if levels are low, that could reduce the ability of the virus to infect people. 

The COVID Human Genetic Effort continues to search for participants, both those who were admitted to a hospital or repeatedly seen at a hospital due to COVID, as well as those who did not get infected, even after “intense and repeated” exposure. 

The number of people likely to be resistant is much smaller, Hsieh said, than the number of people susceptible to severe disease.

The Testing … or Lack Thereof Factor

The timing of testing and a person’s “infection profile” may be factors in people incorrectly declaring themselves NOVIDs, said Anne Wyllie, PhD, a research scientist in epidemiology at the Yale School of Public Health in New Haven, CT, and a co-developer of a saliva PCR test for COVID. 

“Infection profiles can vary between individuals,” she said. For some, the infection may start in the lower respiratory tract, others in the higher respiratory tract. “Depending on where the virus takes up residence, that can affect test results.”

Then there’s the following-instructions factor. “It’s very likely that due to tests not being done at the right time, with the right sample, or not repeated if there are ongoing evidence of symptoms, that there are individuals out there who believe they are NOVIDs but just missed catching their infection at the window of opportunity." Wyllie said.

Susceptibility Research

“The part we have proven is the genetic defect that would make you more susceptible to having severe disease,” Hsieh said. 

Many published papers report that inherited and/or autoimmune deficiencies of type I interferon immunity, important for combating viral infections and modulating the immune response, can be a significant cause of life-threatening COVID pneumonia. 

More recently, researchers, including Jean-Laurent Casanova, MD, PhD, professor at Rockefeller University and co-founder of the COVID Human Genome Effort, reported that deficiencies in a gene that plays a role in built-in immunity (the early response), and a gene involved in signaling within the immune cells, impairs interferon production and may be the basis of severe COVID pneumonia. 

NOVIDs’ Habits Run the Gamut

As scientists continue their research, the NOVIDs have their own ideas about why they’ve dodged the pandemic bullet, and they have a variety of approaches to handling the pandemic now.

Ryan Alexander, the field rep who travels to casinos, is up to date on his vaccinations and has gotten all the recommended COVID shots. “I was wearing a mask when told to wear masks,” he said. 

He still observes the social distance habit but lives life. “I’ve been to three or four concerts in the past couple of years.” 

And does he worry his number will eventually be up? “Not at this point, no,” he said. 

Joe Asher, 46, said he has not gotten COVID despite being in contact with about 100 people a day, on average. He works as a bartender at an Evansville, IN, brewery.

“On a Friday night, we can get 500 people,” he said. “I feel like almost everyone at the brewery got it. There’s no way I wasn’t exposed to it all the time.” 

However, he said, his co-workers who did get sick were very cautious about not infecting others, partly to help protect a co-worker’s family with newborn twins, so that may have helped him stay uninfected, too. 

Asher said he’s in good physical shape, and he’s worked around the public for a long time, so figures maybe that has strengthened his immune system. He’s always been careful about handwashing and said he’s perhaps a bit more conscious of germs than others might be.

Roselyn Mena, 68, a retired teacher in Richmond, CA, about 16 miles northeast of San Francisco, said she’s managed to avoid the virus even though her husband, Jesus Mena, got infected, as did her two adult children. Now, she remains vigilant about wearing a mask. She tries not to eat inside at restaurants. “I’m super careful,” she said. 

Besides her teacher training, Mena had training as a medical assistant and learned a lot about sanitizing methods. She gets an annual flu shot, washes her hands often, and uses hand sanitizer.

When she shops, she will ask salespeople not wearing masks to please mask. “Only one refused, and she got someone else [to wait on her].” 

One reason she is always careful about hygiene, Mena said, is that “when I get a cold, I get really sick. It last and lasts.” Now, she does worry she might still get it, she said, with the prospect of getting long COVID driving that worry.

In the beginning of the pandemic, Rhonda Fleming, 68, of Los Angeles, lived in a "COVID bubble," interacting with just a few close family members. As cases went down, she enlarged the bubble. Her two grown daughters got infected, but her granddaughter did not.

She has been vigilant about masking, she said, “and I do still mask in public places.” She has a mask wardrobe, including basic black as well as glittery masks for dressier occasions. “I always carry a mask because inevitably, a cougher surrounds me.” 

Now, she will bypass restaurants if she doesn’t feel comfortable with the environment, choosing ones with good air flow. When she flew to Mexico recently, she masked on the plane. 

At this point, she said she doesn’t worry about getting infected but remains careful. 

Recently, two friends, who have been as diligent as she has about precautions, got infected, “and they don’t know how they got it.”

Bragging Rights?

Until researchers separate out the true resisters and those who claim to be, some NOVIDs are simply quietly grateful for their luck, while others mention their COVID-free status to anyone who asks or who will listen, and are proud of it.

 

And what about those who wear a “NOVID” T-shirt? 

“I would think they have a need to convey to the world they are different, perhaps special, because they beat COVID,” said Richard B. Joelson, a New York-based doctor of social work, psychotherapist, and author of Help Me! A Psychotherapist’s Tried-and-True Techniques for a Happier Relationship with  Yourself and the People You Love. “They didn’t beat COVID, they just didn’t get it.” 

Or they may be relieved they didn’t get sick, he said, because they feel defeated when they do. So “it’s a source of pride.”  It might be the same people who tell anyone who will listen they never need a doctor or take no medicines, he said.

Even though science may prove many NOVIDs are inaccurate when they call themselves resisters, Hsieh, of the University of Colorado, understands the temptation to talk about it. “It’s kind of cool to think you are supernatural,” she said. “It’s much more attractive than being susceptible. It’s a lot sexier.”