What is immunity debt? What does it mean for cold and flu season?

This fall, America’s pediatric hospitals have been overwhelmed by a “tri-demic” of RSV, flu, and Covid-19. And while it’s not a surprise to see respiratory viral infections hit hard at this time of year, what is surprising is to see so many of these viruses hit so many parts of the country so hard at the same time.

Why is everyone so sick, so simultaneously? One explanation that’s gotten a lot of airtime is the concept of “immunity debt,” coined by a group of French pediatric infectious disease experts in an August 2021 publication.

A central premise of immunity debt is that for many infectious diseases, repeat infections are milder than the first infection. The authors hypothesized that after several pandemic years during which masks, distancing, and ventilation protected so many people from initial infections with a range of viruses, more people than usual would be catching certain diseases for the first — and worst — time now that those protections are not as strongly in place.

At the same time, suboptimal vaccination rates for flu, Covid-19, and other vaccine-preventable diseases — due to pandemic disruptions — meant there would be less protection than usual from vaccine-preventable diseases.

The core concepts of the authors’ idea have been muddled by the internet’s inevitable game of telephone, and some experts reject the term as misleading. Inaccurate interpretations of the concept suggest its originators think the pandemic era somehow broke our immune systems, and are being used to armchair-quarterback the wisdom of masking, school closures, vaccines, and other mitigation measures that saved lives.

In fact, the fundamentals of immunity debt make a lot of sense, immunologists and infectious disease experts told me. While the term is new, the concepts it describes are actually well-trodden ideas in epidemiology.

There are still lots of unanswered questions about why respiratory viral dynamics have taken the shape they have over the past few months and years. For now, here’s what we know about the concept, and how it can be dangerously misinterpreted.

The “debt” in immunity debt is actually a surplus — of infection-susceptible people

When we think of debt, most of us think of a deficit, a lack or low supply of something. It might be more intuitive to instead understand this phenomenon as a surplus of susceptible people, especially children.

That is to say: In pre-pandemic times, young children would be exposed to and develop some immunity to a variety of infections in just the first few years of life. During the pandemic, children were still being born — but they weren’t being exposed to infections at nearly the same rate. That means that in many parts of the world, there are nearly three years’ worth of new children with relatively naive, and therefore vulnerable, immune systems, explained Ron Dagan, a doctor and researcher who specializes in pediatric respiratory infections at Israel’s Ben-Gurion University of the Negev.

“A whole cohort is born without exposure, so all of them will be having much lower antibodies than normal — so there will be much more susceptibility to infections,” Dagan said.

There are a few reasons for this immunological naivete, some of them obvious. Social distancing and masking meant that many babies born during this time simply didn’t have contact with the usual number of other children who might have been sick. For a year, many kids didn’t go to school or day care — places where they traditionally encounter lots of infections. And even though many schools and day cares opened up in the fall of 2021, many had mask mandates in place for staff and children during the coldest part of the year, when opening windows and moving class outdoors were least likely to be used as preventive measures.

But other reasons for lower protection levels have more to do with lower levels of infection in adults — specifically, pregnant adults. During the first year of life, most of babies’ infection protection comes in the form of antibodies passed on to them naturally during pregnancy and breastfeeding. The degree of protection newborns have corresponds to their birthing parent’s level of protection.

“If you’re born to mothers with higher antibody levels, you will be more protected,” said Dagan.

For the first two and a half years of the pandemic — before companies began requiring employees to return to the office, and before other pandemic-era measures became far less commonly used — pregnant people, like other adults, weren’t catching colds as often.

Due to systemic inequities, that reprieve wasn’t experienced to the same extent by all Americans. Still, on a population level, many of the babies born during those years didn’t receive as many antibodies during pregnancy or breastfeeding — and were therefore born more vulnerable to common infections.

Several of the experts I spoke with thought that most of the sick children currently being hospitalized would probably have been hospitalized in 2020 or 2021 if they’d been infected back then. In other words, they said, what makes the current hospitalization surge so large is that it represents a backlog of severe infections that, while inevitable, would have caused less of an onslaught if it had been spread out over two-plus years.

All told, the population is more vulnerable to widespread transmission of some respiratory viruses. And because infections in people without immunity are usually more severe than in people with some immunity, that translates to more people at risk of getting sicker when they catch what would otherwise be a casual winter cold. However, it does not mean our individual immune systems are weak or “out of practice,” say epidemiologists.

This is the key source of confusion, experts tell me. While past colds and illnesses from previous seasons can protect us from current outbreaks conditions, there really isn’t such thing as a “good cold.” We shouldn’t seek out sickness for ourselves or our children. When you go looking for viruses, you never know what you’re going to catch.

Preventing respiratory infections is a good thing. That’s an important fact that misinterpretations of “immunity debt” get wrong.

Remember the hygiene hypothesis? That’s the theory that overly clean environments prevent healthy children’s immune systems from getting the “education” they need to respond adequately to infectious organisms. Without that education, goes the theory, the immune system compensates by overreacting, leading children to develop allergies, asthma, and other problems of immune system dysregulation.

In many people’s imaginations, the hygiene hypothesis means the more colds children are exposed to early in life, the more protective their immune systems are later in life. But there are very real risks with taking an open-door approach to catching colds, said Steven Varga, an immunologist at the University of Iowa who studies viral respiratory infections.

For starters, when it comes to respiratory viruses, you never know what you’re breathing in: a mild virus that will cause a few days of snot, or something more deadly. It’s impossible to game out getting a mild infection, said Varga. “You can’t prevent one kind of respiratory tract infection and allow the others to go through,” he said.

If people are unprotected against less virulent pathogens like rhinovirus, for example, they’re also unprotected against viruses that can cause real damage, like RSV and SARS-CoV-2. That creates threats to those known to be at risk for severe infection from these viruses, like older and immunocompromised people.

Again, trying to get sick on purpose is a dangerous game of roulette. However, Varga cautioned that it’s impossible to predict who will get super-sick with a pathogen — even healthy people can get unexpectedly and severely ill. The vast majority of kids hospitalized for RSV are otherwise healthy, he said. “We can’t predict with any great certainty who is at increased risk for that more severe disease.”

The most helpful germs for our immune system are mostly ingested, not inhaled

There are also misconceptions, the researchers say, about which microbes help “train” our immune system most effectively. It’s not respiratory viruses like the cold and flu.

Rather, it’s the billions of microbes that live peacefully in our bodies, sometimes called the microbiome, said Marsha Wills-Karp, an immunologist at Johns Hopkins Bloomberg School of Public Health who studies the environmental determinants of allergic airway diseases.

Within that microbiome, there are many “teachers,” like bacteria that educate infants’ immune systems to develop lymphoid centers, the B-cell factories that contribute to antibody production, or that train macrophages and other immune cells to respond to pathogenic invaders (i.e., germs).

A lot of work that’s supported the hygiene hypothesis suggests that most of the microbiome’s important immune system education originates in the gut — and, therefore, that what kids swallow contributes more to their immune development than what they breathe in.

Additionally, it’s not currently clear how many of those helpful microbes are viruses — largely because most microbiome work has been on bacteria.

There is a small microbiome in the upper airways and the lungs, but it’s much less diverse than the digestive tract’s, said Wills-Karp. Although the respiratory microbiome does play a role in health and disease states, “in population studies and animal studies, the hygiene hypothesis seems to be more linked to a healthy gut microbiome,” she said.

The bottom line here: There’s currently not much evidence to support the idea that adding more viruses to a person’s respiratory tract does anything to improve the immune system or to otherwise improve health.

Wills-Karp recommends training young immune systems the way you might train a young football player: with players you know they can handle. Kids should run drills with other players their own size, not with an NFL team, “because there’s more potential for you to get hurt with the big boys,” she said. Similarly, immune systems should get trained on the safe environmental and comestible microbes that live in our guts — exposures children and adults get anyway by living in non-sterile environments, but which are enriched by certain factors like living with animals and eating fermented and fiber-rich foods.

The best cold virus is the one you don’t catch

Instead of relying on direct exposure for the little protection it might provide, a safer bet is to train our immune systems using vaccines whenever we can. Flu and Covid-19 vaccines are available now, and RSV vaccines will likely be approved within the next few years.

Also a safer bet — for immune systems young, old, and everywhere in between — is not getting sick to begin with. Wearing masks, maximizing our indoor air’s ventilation and filtration, and other pandemic-era strategies prevent more than just Covid-19.

There are still a ton of unanswered questions about respiratory viruses and how they impact our health later in life. A big one surrounds the link between asthma and severe RSV disease: Babies with bad RSV infections are more likely to go on to develop asthma, but the medical community has never fully understood whether the infection causes the asthma, or instead, whether the factors that predispose a child to asthma make severe RSV more likely.

Other big questions revolve around the cause, treatment, and overall footprint of post-viral syndromes like long Covid, and the role (if any) of viral interference — meaning, when one viral infection reduces or enhances the severity of a second viral infection — in respiratory virus trends. But one of the most pressing questions, said Dagan, involves what we can expect from these pathogens in the near term. Will next year bring another explosive respiratory virus season? Right now it’s impossible to say.

We do know the immunity boost that follows infections with RSV and certain flu strains is probably only enough to protect people for about a year afterward. But overall, viral outbreaks are easier to explain in retrospect than they are to predict (although, it should be noted, the authors of the “immunity debt” paper did accurately foretell the current RSV surge).

“We don’t know how these viruses will behave in the next two or three years,” or what the SARS-CoV-2 virus will look like a year from now, and whether any changes might portend different impacts on children and adults, he said. “There are too many questions that we can ask — and every answer brings you more questions.”

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