In 2011, a farmer in Oklahoma had a bunch of sick pigs. The animals had what looked like the flu.

"Just like a person with respiratory disease, the pigs had labored breathing, maybe a runny nose, cough and potentially a fever," says virologist Benjamin Hause.

At the time, Hause was working at the company Newport Laboratories, which develops custom vaccines for livestock. "We would detect and isolate pathogens from animals. Then we would grow the pathogens in the lab, kill them and formulate vaccines," says Hause, who's now an executive at Cambridge Technologies, another vaccine company.

The Oklahoma farmer took a few samples from the pigs' noses — a bit like how you swab your nose for an at-home COVID test. He sent the samples to Hause so he could figure out what was making the pigs sick.

Hause immediately thought that the regular flu virus was infecting the pigs. "We expected to find influenza A," he says, "because that's the most common problem." It's also the same type of virus that often causes the seasonal flu in people.

But when he and his colleagues grew the virus in the lab, they quickly realized they were wrong. Hause was shocked by what he saw.

"I thought, 'What is this thing? We've never seen anything like this before,' " he says. "Right away, we were concerned that this virus could infect people."

Most infections are a mystery

For decades, scientists thought that animal viruses seldom jump into people. They thought these spillovers were extremely rare. But in the past few years, studies have been showing that this thinking is wrong.

"I don't think [spillover] is extremely rare," says evolutionary virologist Stephen Goldstein at the University of Utah. "I mean, we know this because when people start looking, people find it."

In fact, there's likely a whole group of animal viruses making people sick all over the world that doctors know nothing about. They've been hidden. They masquerade as a regular cold, flu or even pneumonia.

For example, if you have a respiratory infection in the U.S., doctors can identify the pathogen causing the infection only about 40% of the time. There's growing evidence that the other 60% of infections could be caused by animal viruses such as a dog coronavirus found in Malaysia, Haiti and Arkansas, or even possibly the same virus Hause and his colleagues found in those pigs. Recent studies have made clear that this virus floats in the air at farms and is likely infecting people who work there.

It's everywhere they looked

Hause and his colleagues eventually figured out that they had stumbled upon an entirely new influenza virus, unrelated to the ones known to infect people. "It's completely different than influenza A," says virologist Feng Li at the University of Kentucky, who co-led the discovery of the new virus.

Once scientists started looking for signs of infections in other animals, besides pigs, they found it nearly everywhere they looked: in sheep, goats, camels, horses.

But Li says they hit the jackpot when they looked in one particular animal: cows.

"The percentage of cows in the U.S. that have antibodies to influenza D is way, way high," he says. "Whenever you look at herds, about 50% of individual cows have high levels of antibodies to this virus. That was really surprising."

And it's not just cows in Oklahoma but across the whole country, from west to east and north to south, Li says. "From California to Vermont, and North Dakota to Texas, cows are infected with this virus. They are the primary reservoir for the virus."

On top of that, this virus is incredibly stable, Li says. "It can survive at high temperatures and in acidic environments," he says. "That's why scientists have found influenza D in the air at airports in the U.S." They've also found it in the air at chicken farms in Malaysia.

And so the question has become: If this virus can infect so many different animals and is found in so many cows, does it make people sick? Especially the people who work closely with cows on dairy farms or ranches?

Look what they found in human noses

In 2019 and 2020, scientists at Boston University ran a small and simple experiment. They went to five dairy farms in the West and Southwest, and they washed out the workers' noses before and after their shifts working on the farms. Then they looked for influenza D inside the washes.

The researchers studied only 31 workers over the course of only five days. But they found quite a lot of the virus. "We found about two-thirds of the participants were exposed to influenza D at some point during our study period," says environmental epidemiologist Jessica Leibler, who led the study. They published their findings in November in the journal Zoonoses.

While Leibler and colleagues tested only a small number of workers, the high percentage who had the virus in their noses suggests that influenza D is quite likely common on dairy farms in the Southwest. If the virus was rare on the farms, then finding it at such high levels by chance would be highly unlikely. "To me, the findings suggest that if you look for influenza D, you probably will find it," she says.

Now Leibler and her team looked only for an exposure to influenza D. But previous studies have looked for signs of infections in cattle workers in Florida. Specifically, the study tested for influenza D antibodies in the workers' blood.

"They found a really, really high percentage of workers with influenza D antibodies," Leibler says. "Again, it was again a small study, but more than 90% of the workers had antibodies to influenza D, which implies these workers weren't only exposed, but they were also infected."

In contrast, the prevalence of influenza D antibodies in people who don't work on farms was much lower. Only about 18% of the general population showed signs of being infected, researchers reported in the Journal of Clinical Virology.

Now, no one knows yet if influenza D causes any symptoms in people. But altogether, these studies indicate influenza D is likely what's called an emerging virus, Leibler says. It's jumping into people who work with animals, such as dairy farmers, but it's not likely spreading much beyond that.

"This doesn't seem to be something, right now, that the general public is exposed to in a large way," she says. "But it's something that's a concern for these front-line workers exposed on farms."

That's because there's a real risk that the virus could adapt to people as more and more workers are infected, she says. "Influenza viruses mutate rapidly and frequently. So, over time, influenza D can evolve. It could increase its ability to infect humans and be more easily transmitted among humans or it could become more virulent" and start making people sicker.

For that reason, Leibler and her colleagues are calling for more research on, and surveillance of, this new flu to ensure the safety of the dairy workers but also to ensure that the virus doesn't surprise the world as SARS-CoV-2 did.

In fact, Stephen Goldstein of the University of Utah says, to stop the next pandemic before it occurs, scientists and officials should focus on these viruses that have already made the jump into people instead of cataloging viruses in wild animals.

"Doing virus discovery in wild animals is interesting from a scientific standpoint, but from the standpoint of predicting pandemics, I think it's a ridiculous concept," he says. "Instead we need surveillance – active surveillance – in humans and also in domestic animals."

Currently, at least one company – Cambridge Technologies – is working on a vaccine against influenza D for animals. But in general, very few farms are looking out for the virus in animals or workers, Jessica Leibler says.

For comments on this topic, NPR reached out to the National Cattlemen's Beef Association, the lobbying group for cattle ranchers. A spokesperson referred us to the U.S. Department of Agriculture. The USDA, along with the Centers for Disease Control and Prevention, said in emails that, at this point, there isn't any evidence that Influenza D is causing significant harm to livestock, so there aren't currently any surveillance systems in place for livestock or workers.

As Leibler points out, officials and scientists had a similar view of coronaviruses for a long time – that they weren't a major concern because they only caused a cold.

"Sometimes an animal virus doesn't seem to make people very sick and so scientists brush it away as not really important," Leibler says. "That's what scientists thought about coronaviruses for a long time — that they weren't a major concern because they only caused a cold.

"It only took a huge global pandemic to realize that viruses can change really quickly, and you don't know when they're going to change."

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