Endemicity Is Meaningless

Posted by on February 1, 2022 7:00 am
Categories: Everything Else

By now, we’ve all heard some version of how this ends. The same story has certainly been told often enough: We missed our chance to wipe the new coronavirus out, and now we’re stuck with it. Our vaccines are stellar at protecting against serious disease and death, but not comprehensive or durable enough to quash the virus for good. What lies yonder, then, is endemicity—a post-pandemic future in which, some say, our relationship with the virus becomes simple, trifling, and routine, each infection no more concerning than a flu or common cold. Endemicity, so the narrative goes, is how normal life resumes. (Some pundits and politicians would argue that we are, actually, already at endemicity—or, at the very least, we should be acting as if we are.) It is how a devastating pandemic virus ends up docile.

Endemicity promises exactly none of this. Really, the term to which we’ve pinned our post-pandemic hopes has so many definitions that it means almost nothing at all. What lies ahead is, still, a big uncertain mess, which the word endemic does far more to obscure than to clarify. “This distinction between pandemic and endemic has been put forward as the checkered flag,” a clear line where restrictions disappear overnight, COVID-related anxieties are put to rest, and we are “done” with this crisis, Yonatan Grad, an infectious-disease expert at Harvard, told us. That’s not the case. And there are zero guarantees on how or when we’ll reach endemicity, or whether we’ll reach it at all.

[Read: We’re not at endemicity yet]

Even if we could be certain that endemicity was on the horizon, that assuredness doesn’t guarantee the nature of our post-pandemic experience of COVID. There are countless ways for a disease to go endemic. Endemicity says nothing about the total number of infected people in a population at a given time. It says nothing about how bad those infections might get—how much death or disability a microbe might cause. Endemic diseases can be innocuous or severe; endemic diseases can be common or vanishingly rare. Endemicity neither ensures a permanent détente nor promises a return “to 2019,” Abraar Karan, an infectious-disease physician and global-health expert at Stanford, told us. Its only true dictate—and even this one’s shaky, depending on whom you ask—is a modicum of predictability in the average number of people who catch and pass on a pathogen over a set period of time.

Endemicity, then, just identifies a pathogen that’s fixed itself in our population so stubbornly that we cease to be seriously perturbed by it. We tolerate it. Even catastrophically prevalent and deadly diseases can be endemic, as long as the crisis they cause feels constant and acceptable to whoever’s thinking to ask. In a rosy scenario, reasonably high levels of population immunity could bring the virus to heel, and keep it there; its toll would be roughly on par with the flu’s. As coronavirus cases drop from their Omicron highs in the United States and other countries, there’s at least some reason to hope things are bending in that direction. But at its worst, endemicity could lock us into a state of disease transmission that is perhaps as high as some stretches of the pandemic have been—and stays that way.

If endemicity contains a world of possibilities, not all of them good or even better, then it makes a poor goal, and an impractical conceptual framework for any action aimed at managing COVID in the months, years, and decades ahead. Simply declaring endemicity gets us nowhere. It doesn’t answer the real questions about what we want our relationship with this virus to be. And it doesn’t erase the difficult decisions we’ll need to make if we plan to shape that future, rather than risk letting the virus make our choices for us.

It is an unfortunate coincidence that the word endemic begins with end. The arrival of endemicity is actually the beginning—of a long and complicated relationship between a pathogen and its host population. En demos. In the people.

Exactly what kind of long and complicated relationship endemicity denotes, though, is impossible to say, even for experts. “It’s a very nonspecific notion,” Karan said. “There’s really no definition of endemic,” Emily Martin, an epidemiologist at the University of Michigan, told us. And the word is so “muddy and misused” that it’s “really hard to pin down why someone is using it wrong,” Ellie Murray, an epidemiologist at Boston University, told us. We spoke with more than a dozen experts for this article, and nearly every one of them explained endemicity differently.

For some, endemicity entails a disease with stability, constancy. For others, it means one that concentrates in a specific geography. Some think a degree of predictability is a prerequisite; some do not. Others still adhere to a more technical definition: Endemicity refers to a state in which over, say, a year, each person who catches an infection will on average transmit it to one other person, so that the overall case burden neither rises nor falls. Much of the population has at least some immune protection, and the spread of the disease is limited by the rate at which vulnerable people are introduced (or reintroduced) into the population, by birth or waning immunity. Think of a bathtub with water flowing in and draining out at the same rate. But some experts think that notion’s too strict: Any amount of sustained spread, however turbulent, can qualify as endemicity.

[Read: The worst of the Omicron wave could still be coming]

What experts do agree on is that endemicity is not monolithic. The water in that tub might be hot or cold; the level it plateaus at can be very high or very low. The world’s pathogens run the gamut. Viruses such as herpes simplex 1, which causes cold sores and, less commonly, genital herpes, are considered endemic throughout the world. In the United States, HSV-1 affects, by some estimates, at least half of Americans, though most of the infections are asymptomatic or not terribly severe, especially among adults. Malaria, meanwhile, sickens more than 200 million people a year, and kills at least 400,000, most of them under the age of 5. That, too, is endemicity.

Then there are flu viruses—so often held up as the paragon of endemicity, but actually a better example of just how absurdly confusing endemicity can get. In most places, flu viruses are seasonal, surging in the fall and winter, then subsiding in the warmer months. (They circulate year-round in parts of the tropics.) But they can also erupt into pandemics, as they did in 1918, 1968, and 2009, then tick back down. Flu is one of many examples that show why endemic can’t be thought of as the inverse of pandemic; the two terms are not opposite ends of a spectrum. Endemic doesn’t mean the virus is “suddenly not going to hurt us,” Murray said.

Flu viruses actually present such a bizarre case of boom and bust that many researchers don’t consider them to be endemic at all. The experts we spoke with were pretty much evenly split among saying Flu is endemic, Flu is not endemic, and some version of Who knows? or It depends. This set of viruses, the not-endemic camp argues, are just too erratic to warrant the label, even when flu doesn’t reach pandemic proportions. The seasonality seems reliable, but that may not be enough to count as stable. The magnitude and severity of these annual-ish cycles can vary widely; some strains will play nicer with humans than others. One year, a flu virus will kill about 10,000 Americans. Another year, it will kill six times that. The question of the flu’s endemish nature takes on an almost existential cast: What does it mean to expect something?

Others in the not-endemic camp contend that, in addition to being too unpredictable, the flu is also too global. An endemic pathogen, they say, must be restricted to a population in a specific geographical region, rather than “just everywhere,” Seema Lakdawala, a flu virologist at the University of Pittsburgh, told us. (The CDC agrees.) The Emory University virologist Anice Lowen, meanwhile, isn’t so bothered by the flu’s ubiquity. “I would call it endemic to humans,” she said. Martin, of the University of Michigan, doesn’t put herself in either camp. “Things get wiggly,” she said, “when you’ve got something like the flu.”

Pretty much all we can say for sure about the flu is that—as Malia Jones, a population-health expert at the University of Wisconsin at Madison, told us—it is “a huge pain in the butt, but also not a global pandemic, most of the time. Unfortunately, there is not a single word for that.”

Endemic or not, flu might still represent our best benchmark for what post-pandemic COVID will look like.

Yes, okay, it remains true: COVID is not the flu, especially not while the pandemic’s still raging, so many people around the world lack solid immunity to the new coronavirus, and variants burst out at blistering speeds. In the past two years, COVID has already killed more Americans than any flu pandemic we have on record. But the comparison becomes less fraught when we project a lot further—a lot further—into the future. Flu, fundamentally, is another respiratory virus that’s enmeshed itself quite messily into our population. Which makes it, “with caveats, an excellent model” for what might happen next, Martin told us.

Such familiarity might feel comforting, because flu has come to seem pretty normal to us—most people can visualize, maybe even shrug off, its threat. We name a season in honor of the flu; we design drugs and vaccines to battle it. In most of the world, we expect flu infections to intensify in the winter, then trail off again. We expect the viruses to batter older and immunocompromised people at higher rates. We expect our flu shots to slash the risk of hospitalization but allow for less severe infections, which are especially apt to spread among school-age kids. We know flu viruses can shape-shift enough while brewing in human or animal hosts to bamboozle even experienced immune systems, and that several of those strains and subtypes can trouble us with some regularity. We live with multiple postpandemic flus, among them a muted descendant of the virus that caused the deadly 1918 pandemic. We can’t know what COVID’s future is, but flu offers concreteness where everything else feels like mush.

Then again, SARS-CoV-2 is nothing if not a maverick, and it may warp the already disorganized template that flu viruses offer. Like flu shots, COVID shots seem to provide pretty stalwart protection against severe disease, and are arguably much more adept at this job; immunized people infected with the virus are swifter at subduing and purging it than the uninoculated. But the immunity we raise against low-level infections of both flavors has proved to be far more fickle, and needs to be somewhat frequently topped off. Both types of viruses are also pretty ace at splintering themselves into new and sometimes unrecognizable forms. These complementary trends—forgetful bodies, fast-changing viruses—push us to dose against the flu every fall. We could very well need yearly shots for this coronavirus too. Or not. We could still hit the point where a fourth or fifth dose of an mRNA shot, or the introduction of a next-generation COVID vaccine, will lock our anti-infection defenses on high. (But don’t count on it: That threshold of protection is very difficult for our bodies to maintain.) Vaccination frequency will also depend on whether we’re satisfied with preventing severe disease and death or aim to stamp out as many infections as possible—a higher bar than we’ve set, so far, in our anti-flu efforts.

[Read: Will Omicron leave most of us immune?]

How fast and how drastically the coronavirus rejiggers its genome also matters. Flu viruses and coronaviruses are different enough that they can’t be expected to engineer their evolution in an identical way. SARS-CoV-2 has already lobbed several very successful variants at us: first Alpha, then Delta, and now Omicron. The next globe-trotting variant could be a descendant of any of these, or none of them; it could be more virulent, or less. Like Omicron, it will probably be able to sidestep several of our immune defenses, and just how much slipperiness this virus is capable of is “the big open question,” Katia Koelle, an evolutionary virologist at Emory, told us. Maybe the virus is already starting to exhaust its flexibility. Or perhaps the pace at which the coronavirus alters itself will eventually slow as it runs out of super-hospitable hosts, as our colleague Sarah Zhang has reported.

And SARS-CoV-2 could still break the bounds of seasonality, and become a near-year-round threat in some parts of the world, or all of it, which would complicate how and when we vaccinate. “I feel convinced that we’re going to have a winter season of it every year,” Martin told us. “But what’s going to happen outside of winter is the big question—are we going to have summer surges?”

All of these factors—human immunity, virus mutability, and how and when host and pathogen interact—will shape our experience of COVID as a disease. We still don’t know what future COVID will be like. During the pandemic, SARS-CoV-2 has packed a far bigger wallop than the garden-variety flu, prompting more hospitalizations, as well as a bevy of chronic disease. This gap in severity might lessen as population immunity to the coronavirus continues to build through reinfections and revaccinations, but maybe not. SARS-CoV-2 also seems to spread faster than flu viruses, so far. If that pattern holds, that trait, combined with a decent bit of immune-slipperiness, could mean more COVID than flu overall—both on population and individual scales.

The transition between pandemic and post-pandemic also can’t be expected to happen in an instant. We may not know what future COVID looks like until we get there. Given everything we still don’t understand, “like the flu” could actually be an underestimate of the twists and turns ahead.

Even if COVID somehow perfectly pantomimes the flu, that should not come as a relief. “What we’re basically saying is we’re accepting another disease that kills 20,000 to 60,000 people a year,” Grad, of Harvard, said. That’s on top of the many, many other microbes that may pile into our airways during the chilly winter months—respiratory syncytial virus, rhinovirus, other coronaviruses, and a glut of different bacteria, just to name a few. The health-care system already struggles to shoulder this load during the winter, Bill Hanage, an epidemiologist at Harvard, told us. Increasing it “would not be a trivial outcome.”

Yet we’re not at the mercy of the coronavirus’s whims. The post-pandemic period is an armistice between pathogen and host, and that means both parties get to dictate its terms. “You can have endemicity and have a lot of infections, or you can have endemicity and have very few infections,” Karan, of Stanford, told us. “What we do is what determines the difference between those two things.” That, in turn, reflects “how much we care” about a given disease, Brandon Ogbunu, an infectious-disease modeler at Yale, told us.

[Read: America is not ready for Omicron]

Endemic diseases, then, are the shades of suffering we’ve accepted as inevitable, no longer worth haggling down. The term is a resignation to the burden we’re left with. It can reflect unspoken values about whom that disease is affecting, and where, and the value we place on certain people’s well-being. Diseases such as malaria, HIV, and tuberculosis, which concentrate in less wealthy parts of the world, carry pandemic-caliber disease and death rates. And yet, they are commonly called endemic.

COVID could follow suit. Already, rich, Western countries have enjoyed plentiful access to vaccines and treatments. They’ll inevitably find themselves best equipped to declare the crisis over first. But that risks concentrating COVID in the parts of the world least able to fend it off. Claiming endemicity can be a way of shifting disease to the vulnerable, and declaring these inequities tolerable.

The enormous range contained by the endemic umbrella also showcases how human intervention can affect a disease’s impact. We can usher in endemicity (or something like it) by hastening a pandemic’s end. We can reduce endemicity’s boil to a simmer, or entirely ice it out. The level at which a disease first lands doesn’t have to be where it stays. We managed to eradicate smallpox, a once-endemic disease. Polio is in retreat as well, though the COVID pandemic has set many efforts back. Measles, formerly endemic to the United States, now causes only very infrequent outbreaks among Americans, though it is still found in many places abroad. Even malaria, though still a long way off from eradication, has become more manageable than it was before, thanks to dedicated prevention and management campaigns that have equipped at-risk populations with better access to vaccines, treatments, and mosquito control. The World Health Organization has declared its aim to slash malaria cases by at least 90 percent by 2030.

[Read: The coronavirus will surprise us again]

Our window to permanently purge SARS-CoV-2 from the planet has already slammed shut; it’s too widespread, and too many animal species can catch it, and our vaccines are imperfect shields against it. We probably won’t ever eradicate endem-esque influenza either, for very similar reasons, Lakdawala, of the University of Pittsburgh, said. But between what we’re dealing with now and total extinction, there’s a lot of room to “reduce flu’s burden considerably,” she told us. For a while, we inadvertently did: The viruses that cause it all but vanished during our first full pandemic winter, thanks to the masks, school closures, and physical distancing so many people took on to curb the coronavirus’s spread. Preserving just a few of the least disruptive infection-control strategies post-pandemic, even partially, could greatly reduce the flu’s annual toll. COVID’s march toward maybe-endemicity is an opportunity to “reflect on how many different diseases are out there that are preventable,” Grad said.

Using the term endemic imposes a false sense of certainty on a fundamentally uncertain situation. “Everybody wants it to be simplified, but there is so much that we don’t understand yet,” Lakdawala told us. “We’re trying to cram it all into one word, and one word doesn’t cut it.” When we fail to consider the many possibilities that lie ahead—when we treat endemicity as unitary—the term becomes fatalistic. To say that the pandemic will give way to endemicity is to suggest a single end point; saying that SARS-CoV-2 will become endemic suggests that what comes next is up to the pathogen alone. But the post-pandemic phase will be shaped by the choices and actions we make. If our future with it is a truce we strike with the virus, it’s one that we can renegotiate, over and over again.

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