March 9, 2022 -- If you're among those people in the United States who never had COVID-19, how should you think about your risk?

According to the CDC, more than half the people in the U.S. are in the never-got-COVID-19 category.

The CDC estimates that by the end of January, 43.4% in the U.S. had antibodies to the coronavirus triggered by infection, not by vaccination -- suggesting that nearly 60% of people have never been infected.

Now mask mandates are lifting, and daily case and death numbers are plunging. According to the New York Timestracker, new cases are down 51% for the past 2 weeks, and deaths have fallen 30% in that period.

So as those who have so far escaped the virus venture out into reopened environments, should they worry more or less about risk than people who were infected before them?

Some experts weigh in with caution against feeling invincible.

No ‘Suit of Armor’

William Schaffner, MD, an infectious disease expert at Vanderbilt University School of Medicine in Nashville, says science has not been able to determine why some people have been able to be stay COVID-19-free when the virus was raging and exposure was widespread.

He says it's important to remember that though some people think they have never had COVID-19, they may have had the disease without symptoms or blamed mild symptoms on something else.

"People may have conceivably -- but we can't define them yet -- different capacities to ward off viruses or bacteria," Schaffner says.

Could it be that some people have a better immune system or some set of genes, or a particular environmental reason they are less likely to be affected by an infectious disease?

"We can't define that in 2022 medicine, but it could be," he says.

More is known about why people get sicker than others with the same COVID-19 exposure.

"They're more likely to get seriously ill if they have a list of predisposing conditions -- if they're older, if they're frail, if they have underlying illness or are obese. All of those things clearly impair the body's response to virus," Schaffner says.

He warns those who have never been infected, though, not to assume they have "a suit of armor."

All should continue to follow guidance on getting vaccinated, and those vaccinated should continue to get boosted, Schaffner says.

"Clearly, the data show that if you are vaccinated and boosted, you're protected much more securely against severe disease," he says.

If the “never-COVIDs” get a respiratory infection, they should still get tested for COVID-19, Schaffner says.

He says that while both vaccines and previous infection offer protection, how long that protection lasts is not yet known.

"We have to stay tuned," Schaffner says. "There may be a recommendation in the future to get a booster annually or something like that. We need to be open to those down the road."

Amesh Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, says it's unclear why some people have been able to avoid COVID-19

There are probably many reasons for this, he says, and they involve how each person’s immune system reacts differently. That itself is probably based in differences in our genes.

He agrees, also, that many of us were likely infected and never knew it.

Still, he says, this isn't the time to get overconfident with risk-taking where COVID-19 is concerned.

"People who have not knowingly been infected with COVID should be vaccinated, and after that, be assured that they are protected against serious disease from this virus," he says.

Genetic Protection?

A new study in the journal Nature Genetics explains a potential genetic connection.

Study authors found evidence that a particular enzyme called ACE2, which helps regulate blood pressure, wound healing, and inflammation, has also been shown to serve as an open door into cells for some coronaviruses like the one that causes COVID-19.

Manuel A. Ferreira, PhD, executive director for analytic genetics at Regeneron Pharmaceuticals, says ACE2 receptors -- what he calls the "gateways" for the coronavirus -- are different in people who have inherited a particular genetic variant, known as an allele.

The researchers have found that that this particular variant is linked to a lower risk of coronavirus infection.

While the study showed a 40% reduction in infection risk for people with this genetic variant, the researchers could not tell if this can predict how sick a person would get from COVID-19.

Show Sources

CDC: “COVID Data Tracker.”

The New York Times: “Coronavirus in the U.S.: Latest Map and Case Count.”

William Schaffner, MD, infectious disease expert, Vanderbilt University School of Medicine, Nashville.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore.

Nature Genetics: “Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease.”

Manuel A. Ferreira, PhD, executive director for analytical genetics, Regeneron Pharmaceuticals.

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