Updated at 12:05 p.m. ET on June 7, 2024
Our most recent flu pandemic—2009’s H1N1 “swine flu”—was, in absolute terms, a public-health crisis. By scientists’ best estimates, roughly 200,000 to 300,000 people around the world died; countless more fell sick. Kids, younger adults, and pregnant people were hit especially hard.
That said, it could have been far worse. Of the known flu pandemics, 2009’s took the fewest lives; during the H1N1 pandemic that preceded it, which began in 1918, a flu virus infected an estimated 500 million people worldwide, at least 50 million of whom died. Even some recent seasonal flus have killed more people than swine flu did. With swine flu, “we got lucky,” Seema Lakdawala, a virologist at Emory University, told me. H5N1 avian flu, which has been transmitting wildly among animals, has not yet spread in earnest among humans. Should that change, though, the world’s next flu pandemic might not afford us the same break.
Swine flu caught scientists by surprise. At the time, many researchers were dead certain that an H5N1, erupting out of somewhere in Asia, would be the next Big Bad Flu. Their focus was on birds; hardly anyone was watching the pigs. But the virus, a descendant of the devastating flu strain that caused the 1918 pandemic, found its way into swine and rapidly gained the ability to hack into human airway cells. It was also great at traveling airborne—features that made it well positioned to wreak global havoc, Lakdawala said. By the time experts caught on to swine flu’s true threat, “we were already seeing a ton of human cases,” Nahid Bhadelia, the founding director of the Boston University Center on Emerging Infectious Diseases, told me. Researchers had to scramble to catch up. But testing was intermittent, and reporting of cases was inconsistent, making it difficult for scientists to get a handle on the virus’s spread. Months passed before the rollout of a new vaccine began, and uptake was meager. Even in well-resourced countries such as the U.S., few protections hindered the virus’s initial onslaught.
But the worst never came to pass—for reasons that experts still don’t understand. Certainly, compared with the 1918 pandemic, or even those in the 1950s and ’60s, modern medicine was better equipped to test for and treat flu; although vaccine uptake has never been perfect, the availability of any shots increased protection overall, Sam Scarpino, an infectious-disease modeler and the director of AI and life sciences at Northeastern University, told me. Subtler effects may have played a role too. Other H1N1 viruses had been circulating globally since the late 1970s, potentially affording much of the population a degree of immunity, Troy Sutton, a virologist at Pennsylvania State University, told me. Older people, especially, may have harbored an extra dose of defense, from additional exposure to H1N1 strains from the first half of the 20th century. (After the 1918 pandemic, versions of that virus stuck around, and continued to percolate through the population for decades.) Those bonus safeguards might help explain why younger people were so severely affected in 2009, Lakdawala told me.
Some of those same factors could end up playing a role in an H5N1 epidemic. But 2009 represents an imperfect template—especially when so much about this new avian flu remains unclear. True human-to-human spread of H5N1 is still a distant possibility: For that, the virus would almost certainly need to undergo some major evolutionary alterations to its genome, potentially even transforming into something almost unrecognizable. All of this muddies any predictions about how a future outbreak might unfold.
Still, experts are keeping a close eye on a few factors that could raise H5N1’s risks. For instance, no versions of H5N1 flu have ever gained a sustained foothold in people, which means “there’s very little immunity in the community,” Michael Osterholm, the director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told me.
Exposure to other flu strains could offer limited protection. Lakdawala and Sutton have been running experiments in ferrets, which transmit and fall ill with flu much like people do. Their preliminary results suggest that animals with previous exposures to seasonal-flu strains experience milder disease when they’re next hit with this particular H5N1. That said, ferrets with zero prior flu experience—which would be the case for some very young kids—fare poorly, worse than they do with the H1N1 of 2009, and “that’s scary,” Lakdawala told me.
It’s too early to say how those results would translate into people, for whom data are sparse. Since this H5N1 virus was first detected in the 1990s, scientists have recorded hundreds of human cases, nearly half of whom have died. (Avian flus that spill intermittently people often have this kind of nasty track record: This week, the WHO reported that another kind of bird flu, designated H5N2, killed a man in Mexico in late April. It was the flu subtype’s first recorded instance in a human; no evidence suggests yet that this virus has the ability to spread among people, either.) Experts caution strongly against reading too much into the stats: No one can be certain how many people the virus has actually infected, making it impossible to estimate a true fatality rate. The virus has also shape-shifted over decades—and the versions of it that killed those people did not seem capable of spreading among them. As Sutton pointed out, past experiments suggest that the mutations that could make H5 viruses more transmissible might also make them a bit less deadly. That’s not a guarantee, however: The 1918 flu, for instance, “transmitted really well in humans and caused very severe disease,” Sutton said.
Scientists also can’t extrapolate much from the fact that recent H5N1 infections among dairy workers in the U.S. have been documented as mild. Many people who work on farms are relatively young and healthy, Bhadelia noted; plus, their exposures have, presumably, been through virus-laden raw milk. The virus could affect a different community in more dramatic ways, and the nature of the disease could shift if the virus entered the body via another route. And “mildness” in the short term isn’t always a comfort, Scarpino said: As with COVID, the disease could still have chronic consequences for someone’s health.
The world is in some ways better prepared for H5N1 than it was in 2009. Scientists have had eyes on this particular avian flu for decades; in the past few years alone, they’ve watched it hopscotch into dozens of animal species, and tracked the genetic tweaks it’s made. Already, U.S. experts are testing for the pathogen in wastewater, and federal regulators have taken action to halt its spread in poultry and livestock. H5 vaccines are stockpiled, and more are on the way—a pipeline that may be speedier than ever before, thanks to the recent addition of mRNA tech.
But this close to the worst days of the COVID-19 pandemic, Osterholm and others worry that halting any outbreak will be harder than it otherwise would have been. “We could see many, many individuals refusing to get a vaccine,” he said. (That may be especially true if two doses are required for protection.) Bhadelia echoed that concern, adding that she’s already seeing a deluge of misinformation on social media. And Scarpino noted that, after the raging debates over COVID-era school closures, legislators may refuse to entertain the option again—even though children are some of the best conduits for flu viruses. Stopping a pandemic requires trust, coordination, and public buy-in. On that front alone, Osterholm said, “without a doubt, I think we’re less prepared.”
The world has a track record of not taking flu seriously—even, sometimes, when it sparks a pandemic. In the months following the initial outbreaks of swine flu, the outbreak was mocked as a nothingburger; public-health officials were criticized for crying wolf. But the arguably “mild” flu epidemic still filled hospital emergency departments with pneumonia cases, spreading the virus to scores of health-care workers; kids still fell sick in droves. So many young people died that, in terms of years of life lost, Osterholm told me, the toll of 2009 still exceeded those of the flu pandemics that began in 1957 and 1968. Nor are comparisons with seasonal flus exactly a comfort: Most years, those epidemics kill tens of thousands of people in the U.S. alone.
H5N1 could also permanently alter the world’s annual flu burden. An avian-flu pandemic could present the perfect opportunity for this virus to join the other flus that transmit seasonally—becoming endemic threats that may be with us for good. “We’ve seen that with every flu pandemic that’s occurred,” Sutton told me. More circulating flu viruses could mean more flu cases each year—or, perhaps, more chances for these viruses to mingle their genetic material and generate new versions of themselves to which the population lacks immunity.
However likely those possibilities are, halting H5N1’s spread now would preclude all of them. Scientists have foresight on this avian flu in a way they never did with pre-pandemic swine flu. Capitalizing on that difference—perhaps the most important one between these two flus—could keep us from experiencing another outbreak at all.