The COVID Question That Will Take Decades to Answer
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.
[Read: Is COVID a common cold yet?]
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.
[Read: Are our immune systems stuck in 2020?]
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.