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  • The ‘Unthinkable’ New Reality About Bedbugs

    The ‘Unthinkable’ New Reality About Bedbugs

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    This article was originally published by Knowable Magazine.

    The stories have become horribly familiar: houses so overrun by bedbugs that the bloodsucking insects pile an inch deep on the floor. An airport shutting down gates for deep cleaning after the parasites were spotted. Fear and loathing during Fashion Week 2023 in Paris, with bedbug-detection dogs working overtime when the insects turned up in movie theaters and trains.

    For reasons that almost certainly have to do with global travel and poor pest management, bedbugs have resurfaced with a vengeance in 50 countries since the late 1990s. But recently, the resurgence has brought an added twist: When exterminators swarm out to hunt these pests, they might encounter not just one but two different kinds of bugs.

    Besides the common bedbug, Cimex lectularius, which has always made its home in the Northern Hemisphere, there are now sightings of its relative, the tropical bedbug, Cimex hemipterus, in temperate regions. Historically, this species didn’t venture that far from the equator, write the entomologists Stephen Doggett and Chow-Yang Lee in the 2023 issue of the Annual Review of Entomology. But in recent years, tropical bedbugs have turned up in the United States, Sweden, Italy, Norway, Finland, China, Japan, France, Central Europe, Spain—“even in Russia, which would have once been unthinkable,” says Lee, a professor of urban entomology at UC Riverside.

    Like the common bedbug, the tropical version has grown resistant to many standard pesticides—to the point where some experts say they wouldn’t bother spraying should their own home become infested. It has been estimated that the fight against bedbugs is costing the world economy billions annually.

    This all adds up to a sobering new reality: For many people, bedbugs are becoming a fact of life again, much as they used to be throughout humanity’s history. But as scientists race to find new strategies to combat these pests—everything from microfabricated surfaces that entrap the insects to fungal spores that invade and kill them—they also learn more about the often-bizarre biology of bedbugs, which might one day reveal the parasite’s Achilles’ heel.

    Genomics shows that bedbugs emerged 115 million years ago, before the dinosaurs went extinct. When the first humans appeared and moved into caves, the ancestors of today’s bedbugs were ready and waiting. It is thought that these insects initially fed on bats. But bats reduce their blood circulation during their sleeplike torpor state, likely making it harder for the bloodsucking parasite to feed. Presumably, then, at least some bedbug ancestors happily switched to humans.

    Since then, the bugs have followed humankind across the globe, tagging along on ancient shipping routes and modern plane rides. Preserved bedbugs were found in the quarters used by workers in ancient Egypt some 3,550 years ago.

    Bedbugs can survive a year or more without feeding. About as big as flattened apple seeds, they squeeze into tiny cracks in walls or in the joints of bed frames during the day; they crawl out at night, attracted by a sleeper’s exhaled carbon dioxide and body warmth. At the turn of the 20th century, an estimated 75 percent of homes in the U.K. contained bedbugs. Bizarre prescriptions for remedies have circulated down the years, including a recipe for “cat juice” in a pest-control guide from 1725. The formula called for suffocating and skinning a cat, roasting it on a spit, mixing the drippings with egg yolk and oil, and smearing the concoction into crevices around the bed.

    DDT (dichlorodiphenyltrichloroethane) and the pesticides that followed helped bring a few decades’ worth of respite from the 1940s to the 1990s—enough that most people forgot about the insects and didn’t recognize them when they reappeared around the turn of the millennium.

    Doggett and Lee hypothesize that the bloodsuckers’ comeback started in areas of Africa, where common and tropical bedbugs naturally coexist, and where DDT (and, later, other insecticides) were sprayed in bedrooms against malaria-carrying mosquitoes. Initially, this would have killed the majority of bed bugs too. But some resistant ones survived and multiplied.

    Bedbugs suck up more than three times their body weight in blood. As they do, they also take in any viruses or other infectious agents that might circulate in the body of their prey, such as hepatitis B and HIV. They have never been found to transmit these pathogens in the wild—but this doesn’t mean that the parasites are benign. “Bedbugs produce some of the most irritating bites of all insects,” says Doggett, a medical entomologist at Westmead Hospital, in Sydney, Australia. “If I receive one, I don’t sleep, as I react so badly. If there are lots of bedbugs, the bites are horrendous.” There have been cases where people have accidentally set mattresses on fire in desperate attempts to chase off the bugs, sometimes burning down their home in the process.

    Humans aren’t the only ones to react so strongly. The Cimicidae family, to which bedbugs belong, comprises about 100 species. Almost all prefer to bite nonhuman animals, such as birds. Biologists have observed cliff-swallow chicks jumping to their death from heavily infested nests rather than enduring the bites.

    Infestations in which hundreds of bugs may descend upon a bed at night can cause a human sleeper to become anemic. Victims can even develop insomnia, anxiety, and depression. They may find themselves shunned by friends, blacklisted by landlords, and—being sleep-deprived—more prone to car accidents and problems at work.

    Indirectly, at least, bedbugs may cause human deaths. Doggett has noticed that some people in Africa are giving up the bed nets that protect them from mosquitoes and life-threatening malaria infections because bedbugs hide in them. “In some regions, malaria cases are on the rise, and we think that bedbugs are contributing to this,” he says.

    By now, bedbug resistance has been reported against most of the prevalent insecticides, including organochlorines, organophosphates, carbamates, neonicotinoids, aryl pyrroles, and pyrethroids. Some of today’s bedbug strains tolerate pesticide doses that are many thousands of times higher than those that used to consistently kill them. Resistant bedbugs have either developed gene mutations that prevent pesticides from binding effectively to their cells or they produce enzymes that quickly break down the toxins in their body. Others are growing thicker exoskeletons that the poisons can’t easily penetrate.

    An investigation some years back into a hospital in Cleveland discovered that new bedbugs showed up in the facility every 2.2 days on average. And tropical bedbugs seem just as happy in our modern indoors as the common variety does. “Heating and air-conditioning have made our living environments more standardized,” Lee says. “If a tropical bedbug happens to be introduced to a house in Norway, it can now survive there even in winter.”

    Currently, the only bedbug sprays that still tend to work are certain combination products that blend different classes of pesticides. But it’s only a matter of time before these, too, will fail, experts say: Reports of resistance have already been documented. More and more, exterminators incorporate nonchemical approaches such as heat treatments, in which trained professionals warm up rooms to more than 120 degrees Fahrenheit for several hours. They sometimes sprinkle a floury dust called diatomaceous earth around rooms, which clings to those bugs that hide from the heat in wall cracks or under mattresses. The dust abrades the insect’s exoskeleton, dehydrating it to death.

    Such measures—combined with more awareness—have helped plateau, or even partly reverse, the spread of bedbugs in some places. In New York City, for example, bedbug complaints fell by half from 2014 to 2020, from 875 complaints a month to 440, on average. To be sure, that’s still 14 complaints a day.

    But although effective, nonchemical methods tend to work slowly. “It’s very common that an elimination takes one to two or even three months,” says Changlu Wang, an entomologist at Rutgers University. Meanwhile, residents must keep living in their infested quarters.

    Nonchemical measures may also be expensive, because they can require laborious steps such as sealing cracks in walls and physically removing bugs by vacuuming. Although a quick (but increasingly futile) spraying of pesticides may cost a few hundred dollars, mechanical eradications can run as high as several thousand dollars. This puts effective bedbug control out of many people’s reach, making them vulnerable to entrenched infestations that can spread through communities.

    The result is that the epidemic has shifted to the poor, says Michael Levy, an epidemiologist at the University of Pennsylvania: “While many cities now have bedbug policies, very few provide much assistance to those who cannot afford treatment.” A 2016 report on 2,372 low-income apartment units in 43 buildings across four New Jersey cities found that 3.8 percent to 29.5 percent were infested with bedbugs.

    The northward spread of tropical bedbugs complicates matters further. Although the two species look alike, tropical bedbugs have more hair on their legs, which allows them to climb out of many of the smooth-walled traps that are used to monitor homes. This means that infestations could stay undetected longer, Lee says. And the larger a population grows, the harder it is to get rid of.

    To fight back, researchers find inspiration in traditional wisdom. In the Balkan region, homeowners used to spread the leaves of the bean plant Phaseolus vulgaris L. around their beds. The leaves possess tiny hooks on their surface that trap the bugs. Now scientists at UC Irvine are developing a “physical insecticide” in the shape of a synthetic material sporting sharply curved microstructures that mimic those on the bean leaves. These irreversibly impale the feet of the bedbugs, Catherine Loudon, a biology professor at UC Irvine, wrote in a 2022 paper in Integrative and Comparative Biology: “The bugs are unable to get away once they are pierced.”

    Other recent approaches are also rooted in nature. Scientists have found, for example, that essential oils can repel bedbugs. However, the effect is mostly temporary. Certain fungal spores, on the other hand, work permanently. “Basically, the spores go into the body of the bedbug and kill it,” Wang says. At least one product containing the insect-killing fungus Beauveria bassiana is now available in the United States.

    Researchers continue to be fascinated by the biology of this insect, particularly its sex life. Although female bedbugs possess a normal set of genitalia, the males typically mate by stabbing a needle-sharp penis straight into the female’s abdomen to inject sperm. They usually do this just after a female bedbug has fed, because this makes her too engorged to protect herself.

    Having to cope with these frequent injuries has led female bedbugs to evolve the only immunity organ in the insect kingdom, says Klaus Reinhardt, a zoologist at the Dresden University of Technology, in Germany. They have also evolved a remarkably elastic material that covers the parts of their abdomen most likely to be stabbed. “It resembles one of those self-sealing injection bottles that close up again when you pull the needle,” Reinhardt says.

    Although this knowledge will likely do little to combat these pests directly, answering another question might: Why don’t bedbugs stay on their host’s body, as lice do? As it turns out, bedbugs don’t like our smell. Certain lipids in human skin repel the bugs, according to a 2021 study in Scientific Reports. This makes them retreat to daytime hiding places, marking their trails with pheromones.

    Already, exterminators try to trap bedbugs with fake trail markings. And one day, we might deter the insects from spreading by treating suitcases with smells they despise.

    But for now, caution remains the best approach. Experts advise that travelers check accommodations for bedbug-defecation stains: on mattress seams and furniture, and behind headboards. (The insects poop as frequently as a few dozen times after every blood meal, often right next to their victims.) Suitcases should be kept in the hotel bathtub or wrapped in a plastic bag. Upon arrival back home, the luggage’s contents should be put into the clothes dryer for at least 30 minutes at the highest setting, or into a very cold freezer for several days.

    If bedbugs do invade a home, “the biggest mistake is to try and get rid of them on one’s own,” Doggett says. “The average person doesn’t appreciate how challenging it is to control bedbugs and will use supermarket insecticides that are labeled for bedbugs but don’t work. The infestation will spread, and the costs escalate.”

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    Ute Eberle

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  • The CRISPR Era Is Here

    The CRISPR Era Is Here

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    When Victoria Gray was still a baby, she started howling so inconsolably during a bath that she was rushed to the emergency room. The diagnosis was sickle-cell disease, a genetic condition that causes bouts of excruciating pain—“worse than a broken leg, worse than childbirth,” one doctor told me. Like lightning crackling in her body is how Gray, now 38, has described the pain. For most of her life, she lived in fear that it could strike at any moment, forcing her to drop everything to rush, once again, to the hospital.

    After a particularly long and debilitating hospitalization in college, Gray was so weak that she had to relearn how to stand, how to use a spoon. She dropped out of school. She gave up on her dream of becoming a nurse.

    Four years ago, she joined a groundbreaking clinical trial that would change her life. She became the first sickle-cell patient to be treated with the gene-editing technology CRISPR—and one of the first humans to be treated with CRISPR, period. CRISPR at that point had been hugely hyped, but had largely been used only to tinker with cells in a lab. When Gray got her experimental infusion, scientists did not know whether it would cure her disease or go terribly awry inside her. The therapy worked—better than anyone dared to hope. With her gene-edited cells, Gray now lives virtually symptom-free. Twenty-nine of 30 eligible patients in the trial went from multiple pain crises every year to zero in 12 months following treatment.

    The results are so astounding that this therapy, from Vertex Pharmaceuticals and CRISPR Therapeutics, became the first CRISPR medicine ever approved, with U.K. regulators giving the green light earlier this month; the FDA appears prepared to follow suit in the next two weeks. No one yet knows the long-term effects of the therapy, but today Gray is healthy enough to work full-time and take care of her four children. “Now I’ll be there to help my daughters pick out their wedding dresses. And we’ll be able to take family vacations,” she told NPR a year after her treatment. “And they’ll have their mom every step of the way.”

    The approval is a landmark for CRISPR gene editing, which was just an idea in an academic paper a little more than a decade ago—albeit one already expected to cure incurable diseases and change the world. But how, specifically? Not long after publishing her seminal research, Jennifer Doudna, who won the Nobel Prize in Chemistry with Emmanuelle Charpentier for their pioneering CRISPR work, met with a doctor on a trip to Boston. CRISPR could cure sickle-cell disease, he told her. On his computer, he scrolled through DNA sequences of cells from a sickle-cell patient that his lab had already edited with CRISPR. “That, for me, personally, was one of those watershed moments,” Doudna told me. “Okay, this is going to happen.” And now, it has happened. Gray and patients like her are living proof of gene-editing power. Sickle-cell disease is the first disease—and unlikely the last—to be transformed by CRISPR.


    All of sickle-cell disease’s debilitating and ultimately deadly effects originate from a single genetic typo. A small misspelling in Gray’s DNA—an A that erroneously became a T—caused the oxygen-binding hemoglobin protein in her blood to clump together. This in turn made her red blood cells rigid, sticky, and characteristically sickle shaped, prone to obstructing blood vessels. Where oxygen cannot reach, tissue begins to die. Imagine “if you put a tourniquet on and walked away, or if you were having a heart attack all the time,” says Lewis Hsu, a pediatric hematologist at the University of Illinois at Chicago. These obstructions are immensely painful, and repeated bouts cause cumulative damage to the body, which is why people with sickle cell die some 20 years younger on average.

    Not everyone with the sickle-cell mutation gets quite so sick. As far back as the 1940s, a doctor noticed that the blood of newborns with sickle-cell disease did not, surprisingly, sickle very much. Babies in the womb actually make a fetal version of the hemoglobin protein, whose higher affinity for oxygen pulls the molecule out of their mother’s blood. At birth, a gene that encodes fetal hemoglobin begins to turn off. But adults do sometimes still make varying amounts of fetal hemoglobin, and the more they make, scientists observed, the milder their sickle-cell disease, as though fetal hemoglobin had stepped in to replace the faulty adult version. Geneticists eventually figured out the exact series of switches our cells use to turn fetal hemoglobin on and off. But there, they remained stuck: They had no way to flip the switch themselves.

    Then came CRISPR. The basic technology is a pair of genetic scissors that makes fairly precise cuts to DNA. CRISPR is not currently capable of fixing the A-to-T typo responsible for sickle cell, but it can be programmed to disable the switch suppressing fetal hemoglobin, turning it back on. Snip snip snip in billions of blood cells, and the result is blood that behaves like typical blood.

    Sickle cell was a “very obvious” target for CRISPR from the start, says Haydar Frangoul, a hematologist at the Sarah Cannon Research Institute in Nashville, who treated Gray in the trial. Scientists already knew the genetic edits necessary to reverse the disease. Sickle cell also has the advantage of affecting blood cells, which can be selectively removed from the body and gene-edited in the controlled environment of a lab. Patients, meanwhile, receive chemotherapy to kill the blood-producing cells in their bone marrow before the CRISPR-edited ones are infused back into their body, where they slowly take root and replicate over many months.

    It is a long, grueling process, akin to a bone-marrow transplant with one’s own edited cells. A bone-marrow transplant from a donor is the one way doctors can currently cure sickle-cell disease, but it comes with the challenge of finding a matched donor and the risks of an immune complication called graft-versus-host disease. Using CRISPR to edit a patient’s own cells eliminates both obstacles. (A second gene-based therapy, using a more traditional engineered-virus technique to insert a modified adult hemoglobin gene into DNA semi-randomly, is also expected to receive FDA approval  for sickle-cell disease soon. It seems to be equally effective at preventing pain crises so far, but development of the CRISPR therapy took much less time.)

    In another way, though, sickle-cell disease is an unexpected front-runner in the race to commercialize CRISPR. Despite being one of the most common genetic diseases in the world, it has long been overlooked because of whom it affects: Globally, the overwhelming majority of sickle-cell patients live in sub-Saharan Africa. In the U.S., about 90 percent are of African descent, a group that faces discrimination in health care. When Gray, who is Black, needed powerful painkillers, she would be dismissed as an addict seeking drugs rather than a patient in crisis—a common story among sickle-cell patients.

    For decades, treatment for the disease lagged too. Sickle-cell disease has been known to Western medicine since 1910, but the first drug did not become available until 1998, points out Vence Bonham, a researcher at the National Human Genome Research Institute who studies health disparities. In 2017, Bonham began convening focus groups to ask sickle-cell patients about CRISPR. Many were hopeful, but some had misgivings because of the history of experimentation on Black people in the U.S. Gray, for her part, has said she never would have agreed to the experimental protocol had she been offered it at one of the hospitals that had treated her poorly. Several researchers told me they hoped the sickle-cell therapy would make a different kind of history: A community that has been marginalized in medicine is the first in line to benefit from CRISPR.


    Doctors aren’t willing to call it an outright “cure” yet. The long-term durability and safety of gene editing are still unknown, and although the therapy virtually eliminated pain crises, Hsu says that organ damage can accumulate even without acute pain. Does gene editing prevent all that organ damage too? Vertex, the company that makes the therapy, plans to monitor patients for 15 years.

    Still, the short-term impact on patients’ lives is profound. “We wouldn’t have dreamed about this even five, 10 years ago,” says Martin Steinberg, a hematologist at Boston University who also sits on the steering committee for Vertex. He thought it might ameliorate the pain crises, but to eliminate them almost entirely? It looks pretty damn close to a cure.

    In the future, however, Steinberg suspects that this currently cutting-edge therapy will seem like only a “crude attempt.” The long, painful process necessary to kill unedited blood cells makes it inaccessible for patients who cannot take months out of their life to move near the limited number of transplant centers in the U.S.—and inaccessible to patients living with sickle-cell disease in developing countries. The field is already looking at techniques that can edit cells right inside the body, a milestone recently achieved in the liver during a CRISPR trial to lower cholesterol. Scientists are also developing versions of CRISPR that are more sophisticated than a pair of genetic scissors—for example, ones that can paste sequences of DNA or edit a single letter at a time. Doctors could one day correct the underlying mutation that causes sickle-cell disease directly.

    Such breakthroughs would open CRISPR up to treating diseases that are out of reach today, either because we can’t get CRISPR into the necessary cells or because the edit is too complex. “I get emails now daily from families all over the world asking, ‘My son or my loved one has this disease. Can CRISPR fix it?’” says Frangoul, who has become known as the first doctor to infuse a sickle-cell patient in a CRISPR trial. The answer, usually, is not yet. But clinical trials are already under way to test CRISPR in treating cancer, diabetes, HIV, urinary tract infections, hereditary angioedema, and more. We have opened the book on CRISPR gene editing, Frangoul told me, but this is not the final chapter. We may still be writing the very first.

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    Sarah Zhang

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  • The COVID Question That Will Take Decades to Answer

    The COVID Question That Will Take Decades to Answer

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    To be a newborn in the year 2023—and, almost certainly, every year that follows—means emerging into a world where the coronavirus is ubiquitous. Babies might not meet the virus in the first week or month of life, but soon enough, SARS-CoV-2 will find them. “For anyone born into this world, it’s not going to take a lot of time for them to become infected,” maybe a year, maybe two, says Katia Koelle, a virologist and infectious-disease modeler at Emory University. Beyond a shadow of a doubt, this virus will be one of the very first serious pathogens that today’s infants—and all future infants—meet.

    Three years into the coronavirus pandemic, these babies are on the leading edge of a generational turnover that will define the rest of our relationship with SARS-CoV-2. They and their slightly older peers are slated to be the first humans who may still be alive when COVID-19 truly hits a new turning point: when almost everyone on Earth has acquired a degree of immunity to the virus as a very young child.

    That future crossroads might not sound all that different from where the world is currently. With vaccines now common in most countries and the virus so transmissible, a significant majority of people have some degree of immunity. And in recent months, the world has begun to witness the consequences of that shift. The flux of COVID cases and hospitalizations in most countries seems to be stabilizing into a seasonal-ish sine wave; disease has gotten, on average, less severe, and long COVID seems to be somewhat less likely among those who have recently gotten shots. Even the virus’s evolution seems to be plodding, making minor tweaks to its genetic code, rather than major changes that require another Greek-letter name.

    But today’s status quo may be more of a layover than a final destination in our journey toward COVID’s final form. Against SARS-CoV-2, most little kids have fared reasonably well. And as more babies have been born into a SARS-CoV-2-ridden world, the average age of first exposure to this coronavirus has been steadily dropping—a trend that could continue to massage COVID-19 into a milder disease. Eventually, the expectation is that the illness will reach a stable nadir, at which point it may truly be “another common cold,” says Rustom Antia, an infectious-disease modeler at Emory.

    The full outcome of this living experiment, though, won’t be clear for decades—well after the billions of people who encountered the coronavirus for the first time in adulthood are long gone. The experiences that today’s youngest children have with the virus are only just beginning to shape what it will mean to have COVID throughout a lifetime, when we all coexist with it from birth to death as a matter of course.


    At the beginning of SARS-CoV-2’s global tear, the coronavirus was eager to infect all of us, and we had no immunity to rebuff its attempts. But vulnerability wasn’t just about immune defenses: Age, too, has turned out to be key to resilience. Much of the horror of the disease could be traced to having not only a large population that lacked protection against the virus—but a large adult population that lacked protection against the virus. Had the entire world been made up of grade-schoolers when the pandemic arrived, “I don’t think it would have been nearly as severe,” says Juliet Pulliam, an infectious-disease modeler at Stellenbosch University, in South Africa.

    Across several viral diseases—polio, chicken pox, mumps, SARS, measles, and more—getting sick as an adult is notably more dangerous than as a kid, a trend that’s typically exacerbated when people don’t have any vaccinations or infections to those pathogens in their rearview. The manageable infections that strike toddlers and grade-schoolers may turn serious when they first manifest at older ages, landing people in the hospital with pneumonia, brain swelling, even blindness, and eventually killing some. When scientists plot mortality data by age, many curves bend into “a pretty striking J shape,” says Dylan Morris, an infectious-disease modeler at UCLA.

    The reason for that age differential isn’t always clear. Some of kids’ resilience probably comes from having a young, spry body, far less likely to be burdened with chronic medical conditions that raise severe disease risk. But the quick-wittedness of the young immune system is also likely playing a role. Several studies have found that children are much better at marshaling hordes of interferon—an immune molecule that armors cells against viruses—and may harbor larger, more efficient cavalries of infected-cell-annihilating T cells. That performance peaks sometime around grade school or middle school, says Janet Chou, a pediatrician at Boston Children’s Hospital. After that, our molecular defenses begin a rapid tumble, growing progressively creakier, clumsier, sluggish, and likelier to launch misguided attacks against the tissues that house them. By the time we’re deep into adulthood, our immune systems are no longer sprightly, or terribly well calibrated. When we get sick, our bodies end up rife with inflammation. And our immune cells, weary and depleted, are far less unable to fight off the pathogens they once so easily trounced.

    Whatever the explanations, children are far less likely to experience serious symptoms, or to end up in the hospital or the ICU after being infected with SARS-CoV-2. Long COVID, too, seems to be less prevalent in younger cohorts, says Alexandra Yonts, a pediatrician at Children’s National Hospital. And although some children still develop MIS-C, a rare and dangerous inflammatory condition that can appear weeks after they catch the virus, the condition “seems to have dissipated” as the pandemic has worn on, says Betsy Herold, the chief of pediatric infectious disease at the Children’s Hospital at Montefiore, in the Bronx.

    Should those patterns hold, and as the age of first exposure continues to fall, COVID is likely to become less intense. The relative mildness of childhood encounters with the virus could mean that almost everyone’s first infection—which tends, on average, to be more severe than the ones that immediately follow—could rank low in intensity, setting a sort of ceiling for subsequent bouts. That might make concentrating first encounters “in the younger age group actually a good thing,” says Ruian Ke, an infectious-disease modeler at Los Alamos National Laboratory.

    COVID will likely remain capable of killing, hospitalizing, and chronically debilitating a subset of adults and kids alike. But the hope, experts told me, is that the proportion of individuals who face the worst outcomes will continue to drop. That may be what happened in the aftermath of the 1918 flu pandemic, Antia, of Emory, told me: That strain of the virus stuck around, but never caused the same devastation again. Some researchers suspect that something similar may have even played out with another human coronavirus, OC43: After sparking a devastating pandemic in the 19th century, it’s possible that the virus no longer managed to wreak much more havoc than a common cold in a population that had almost universally encountered it early in life.


    Such a fate for COVID, though, isn’t a guarantee. The virus’s propensity to linger in the body’s nooks and crannies, sometimes causing symptoms that last many months or years, could make it an outlier among its coronaviral kin, says Melody Zeng, an immunologist at Cornell University. And even if the disease is likely to get better than what it is now, that is not a very high bar to clear.

    Some small subset of the population will always be naive to the virus—and it’s not exactly a comfort that in the future, that cohort will almost exclusively be composed of our kids. Pediatric immune systems are robust, UCLA’s Morris told me. But “robust is not the same as infallible.” Since the start of the pandemic, more than 2,000 Americans under the age of 18 have died from COVID—a small fraction of total deaths, but enough to make the disease a leading cause of death for children in the U.S. MIS-C and long COVID may not be common, but their consequences are no less devastating for the children who experience them. Some risks are especially concentrated among our youngest kids, under the age 5, whose immune defenses are still revving up, making them more vulnerable than their slightly older peers. There’s especially little to safeguard newborns just under six months, who aren’t yet eligible for most vaccines—including COVID shots—and who are rapidly losing the antibody-based protection passed down from their mothers while they were in the womb.

    A younger average age of first infection will also probably increase the total number of exposures people have to SARS-CoV-2 in a typical lifetime—each instance carrying some risk of severe or chronic disease. Ke worries the cumulative toll that this repetition could exact: Studies have shown that each subsequent tussle with the virus has the potential to further erode the functioning or structural integrity of organs throughout the body, raising the chances of chronic damage. There’s no telling how many encounters might push an individual past a healthy tipping point.

    Racking up exposures also won’t always bode well for the later chapters of these children’s lives. Decades from now, nearly everyone will have banked plenty of encounters with SARS-CoV-2 by the time they reach advanced age, Chou, from Boston Children’s Hospital, told me. But the virus will also continue to change its appearance, and occasionally escape the immunity that some people built up as kids. Even absent those evasions, as their immune systems wither, many older people may not be able to leverage past experiences with the disease to much benefit. The American experience with influenza is telling. Despite a lifetime of infections and available vaccines, tens of thousands of people typically die annually of the disease in the United States alone, says Ofer Levy, the director of the Precision Vaccines Program at Boston Children’s Hospital. So even with the expected COVID softening, “I don’t think we’re going to reach a point where it’s, Oh well, tra-la-la,” Levy told me. And the protection that immunity offers can have caveats: Decades of research with influenza suggest that immune systems can get a bit hung up on the first versions of a virus that they see, biasing them against mounting strong attacks against other strains; SARS-CoV-2 now seems to be following that pattern. Depending on the coronavirus variants that kids encounter first, their responses and vulnerability to future bouts of illness may vary, says Scott Hensley, an immunologist at the University of Pennsylvania.

    Early vaccinations—that ideally target multiple versions of SARS-CoV-2—could make a big difference in reducing just about every bad outcome the virus threatens. Severe disease, long COVID, and transmission to other children and vulnerable adults all would likely be “reduced, prevented, and avoided,” Chou told me. But that’s only if very young kids are taking those shots, which, right now, isn’t at all the case. Nor are they necessarily getting protection passed down during gestation or early life from their mothers, because many adults are not up to date on COVID shots.

    Some of these issues could, in theory, end up moot. A hundred or so years from now, COVID could simply be another common cold, indistinguishable in practice from any other. But Morris points out that this reality, too, wouldn’t fully spare us. “When we bother to look at the burden of the other human coronaviruses, the ones who have been with us for ages? In the elderly, it’s real,” he told me. One study found that a nursing-home outbreak of OC43—the purported former pandemic coronavirus—carried an 8 percent fatality rate; another, caused by NL63, killed three out of the 20 people who caught it in a long-term-care facility in 2017. These and other “mild” respiratory viruses also continue to pose a threat to people of any age who are immunocompromised.

    SARS-CoV-2 doesn’t need to follow in those footsteps. It’s the only human coronavirus against which we have vaccines—which makes the true best-case scenario one in which it ends up even milder than a common cold, because we proactively protect against it. Disease would not need to be as inevitable; the vaccine, rather than the virus, could be the first bit of intel on the disease that kids receive. Tomorrow’s children probably won’t live in a COVID-free world. But they could at least be spared many of the burdens we’re carrying now.

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    Katherine J. Wu

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