As autumn faded to winter last year, a few infectious disease researchers started turning their attention away from the Covid-19 pandemic and back to something more familiar. This was the time of year they’d ordinarily start looking at their numbers for influenza, the seasonal flu—to see how bad the outbreak would be, and to assess how well that year’s vaccine dealt with the protean respiratory virus.
The answer was: bupkis. Hardly anyone was sick or dying from the flu. A year earlier, during the 2019–20 flu season—basically fall and winter, peaking in December, January, and February—18 million people in the US saw a doctor for their symptoms, and 400,000 had to be hospitalized. Overall, 32,000 people died. But in the current season, cases barely crossed four digits. “There’s always vaccine season and flu season. We’re used to working in that pattern, and the pattern is gone,” says Emily Martin, an epidemiologist at the University of Michigan School of Public Health who’s part of the Centers for Disease Control and Prevention’s flu-monitoring network. “Now, I’m glad I didn’t have to do Covid control and influenza control at the same time. That would have been a disaster. But at the same time, it is this strange year.”
Strange indeed. And it’s not just the flu. Case numbers for respiratory syncytial virus, which primarily affects babies and, like influenza, has a seasonal rhythm, also bottomed out. According to a paper that came out last week, the missing-in-action list also includes enterovirus D68, a likely culprit behind the polio-like kids’ disease acute flaccid myelitis. The virus and AFM come and go on a roughly every-other-year cycle, and the last round in North America was in 2018. In 2020, they, too, missed their cue.
The why of it isn’t really a mystery. Probably. Most likely, all the mask wearing, physical distancing, handwashing, and other “non-pharmaceutical interventions” that everyone—OK, almost everyone—did to prevent the spread of Covid-19 also put the kibosh on those other viruses. That’s not the only hypothesis going, but it’s a good one.
The mystery is the how and the what-next. The answers might teach scientists more about how those other diseases infect people, and about how to stop them. The mechanics of why those NPIs crushed at least three other respiratory viruses while Covid-19 ran rampant aren’t clear. And even less clear is what a Year Without a Flu will mean for next winter, and for winters after that. Influenza kills anywhere from 12,000 to 61,000 people in the US every year and costs the economy $11 billion annually, according to one estimate. For decades, centuries even, people have just sort of accepted that risk. But if it turns out it’s almost entirely preventable, will people’s willingness to tolerate the risk change too?
Pandemics happen when a virus hits its evolutionary groove. The virus that causes Covid-19 is called SARS-CoV-2, and when it dropped in late 2019, no human immune system had ever seen it before. Nobody had any defenses. The fact that people who didn’t have any symptoms could transmit it made it different from most of its respiratory-pathogen cousins—just different enough to take advantage of human social interactions and go global.
But just as it takes only the smallest circumstance or genetic twist to turn a virus into a pandemic, the disease version of an arena-filling band, it doesn’t take much to limit a disease to the equivalent of playing small clubs, either. “The Covid-19 control measures—mask wearing and social distancing—really work, and they work really well for other respiratory pathogens too,” says Rachel Baker, an epidemiologist at Princeton University. The key difference is probably that those other diseases have been playing gigs for thousands of years, and humans are a little bit inured to their charms. Even the flu, with its famously mutable genome that requires a new vaccine every year, leaves behind some level of population-scale immunity. “With the seasonal diseases, we have a lot of population immunity, we have vaccines, and most people over 2 years old have had RSV,” Baker says. “That’s why you don’t have a seasonal pandemic.”
It’s possible, though perhaps less likely, that some other dynamic beyond the NPIs might be at work. One hypothesis points to “viral interference,” the idea that a sufficiently badass respiratory pathogen could so occupy a susceptible population that it’d essentially supplant other, wimpier viruses. Maybe their immune systems are cranking so hard to fight off the one that the others get caught in the immunological slipstream. “There’s this other mechanism where infected or nearby cells can enter a refractory period where they won’t be susceptible to infection by a virus,” says Pejman Rohani, an infectious disease modeler at the University of Georgia. Or maybe putting everyone on lockdown simply cut the number of contacts between infected people and susceptible ones.
Whatever the mechanism, it seems clear that flu, RSV, and EV-D68 just don’t spread as well as SARS-CoV-2. An epidemiologist might say that the Covid-causing virus has a higher effective reproductive number, or “higher Rt”—the number of people each infected person can go on to infect, over time, given changes in behavior, vaccination, and so on. These diseases, with similar modes of infection, have dissimilar values for Rt.
Things are even more complicated. Masks and all the other disease-fighting rigamarole didn’t stop every other respiratory virus. Rhinoviruses—the “common cold”—and respiratory adenoviruses have continued to circulate this year. Maybe it’s that adenoviruses have DNA as their genetic material instead of RNA, as coronaviruses do? “Surface transmission and long persistence of infection is more of a problem with this one than with the RNA respiratory viruses. I can imagine that the transmission patterns of adenovirus are different enough from SARS-CoV-2 that it wouldn't be as infectious,” Martin says. (Despite early fears, surface transmission, via “fomites,” seems not to have been an issue for Covid-19.) “For rhinovirus, I'm stumped—it may have a higher Rt than we thought.”
Some of the same questions about SARS-CoV-2—how much virus it takes to infect a new host, the vagaries of how it spreads—are still in play with other, more nominally familiar viruses, as well. “It’s slightly embarrassing that we end up saying, ‘Sure, it’s possible,’ especially when there’s a pandemic going on,” Rohani says. “But we’re at the limits of what we know about some of these things.”
What worries modelers, though, isn’t so much the flu-less winter of 2020-21 but the next seasons for the flu, RSV, and EV-D68. Epidemiologic models that establish parameters for counting the numbers of susceptible, infected, and recovered people—SIR models—show some variation of the same worrisome outcome: After a season in which none of the susceptible people turn into infected people, the next season is a lot worse. “We know that for both influenza and RSV, your antibody protection wanes over time. Now we’ve got an entire population that’s had no boost,” Martin says. “If we’re not even having those low level exposures, it really means an open playing field for the viruses next season.”
Models show the same pattern for enterovirus D68, and probably for acute flaccid myelitis too. That virus’s biennial up-and-down is all about the ebb and flow of susceptible populations. “When you have a large outbreak, a lot of people develop it in the community. You need time—usually through a birth cohort—to have the susceptible population reach a certain threshold, and then you can have another outbreak,” says Sang Woo Park, an ecology and evolutionary biology PhD student at Princeton and the lead author of the paper on the disease I mentioned earlier. “One of the concerns, though, would be that, if you keep NPIs like this, eventually the susceptibility will get high enough, and you’ll get a big outbreak.”
If all that’s true … well, do you want the good news or the bad news? The good news is, maybe kids won’t get RSV until they’re older, when it’s usually a milder disease. (“Perhaps that’s better for them,” Martin says, “but we really don’t know.”) And maybe, since influenza didn’t have the chance to jump from person to person and give clever new genetic reassortments a chance to take hold, last year’s vaccine might still confer protection this coming season. Maybe.
The bad news is, if the next influenza strain is quite a lot different than the one scientists built the last vaccine for, they might not be ready. Usually the flu oscillates from hemisphere to hemisphere, winter to winter, like a fabulously wealthy skiing enthusiast. And vaccine-makers could watch what happened in one hemisphere to prepare in the other. But not this year. In its guidance for the coming season, the World Health Organization simply had less to go on. “You had this cadence that’s been interrupted,” Martin says. “Now we don’t have enough data to get a good sense of where it’s going.”
Yet that bad news could still get obviated by better news—if people like you and me start thinking differently about disease and risk. Maybe you did the Covid math for yourself and thought, “Hey, I’m young and comorbidity-free enough to not worry about any of the possible-but-remote outcomes if I get sick. (And I’m not bothered by the possibility of my transmitting the disease to someone else.)” That sounds callous (because it is), but most US residents have done similar math when it comes to the flu. That disease kills tens of thousands of people in this country every year, including a couple hundred children, and the US as a society sees that as merely the cost of doing business indoors year-round, lest the economy take some sort of seasonal hit. The pumpkin spice lattes must flow. As the CDC notes, vaccine uptake numbers vary widely by state, but in the US overall for the 2019–20 season, 63.8 percent of children and 48.4 percent of adults got their flu shot. The rest are … doing some other kind of math.
Now it turns out that maybe those people didn’t have to die. SARS-CoV-2 took hold because it’s a trickster, a stealthy assassin that can ride a human host with no symptoms and still infect others. But most respiratory pathogens aren’t that slick. “One thing I sometimes forget—and have to remind myself of—is that for influenza, RSV, respiratory enterovirus, all of these, is that when you prevent somebody from traveling in spaces and interacting when they’re symptomatic, you can do a lot to prevent transmission of the virus,” Martin says. This means that preventing widespread respiratory disease outbreaks might be as easy as doing something that sounds un-American: Don’t go to work if you’re sick.
Yes, sure, the “susceptible” population will be bigger next season, a vast pool of people ready to convert to “infected.” But the way to keep those S-types from converting to I-types is to make sure they never meet an I-type in the first place. “I think this changes how we think about paid leave, about structures we can put in place so people don't have to work when they’re sick,” Martin says. “If you’re sick, it is not only your responsibility to stay home and not infect other people, but now so many employers and schools and groups have invested in making that possible. I’m hoping that stays.”
A few weeks back I was talking about post-vaccination behavior with Grace Lee, an infectious disease physician at Stanford Children’s Health and member of the CDC’s Advisory Committee on Immunization Practices. At the time, Lee almost offhandedly suggested that maybe people’s new risk awareness about Covid-19 and the relative ease with which flu got stamped out might make people rethink their tolerance of the flu’s toll. So I called her back to ask whether she thought the models might be wrong—whether she thought a Year Without a Flu might inspire people to go for Year Without a Flu 2.
“We became numb to it, to a certain extent, with flu. My hope is that more people will be mindful of others now, and recognize that we can prevent flu by vaccination,” Lee says. “Maybe this gives us a common language and a place to start.”