Bird flu researchers turn to Finland’s mink farms, tracking a virus with pandemic potential

HELSINKI — It was the quiet that stood out to Tarja Sironen at the fur farm.

A specialist in emerging infectious diseases, Sironen has conducted research at fur farms for years. She helped develop a Covid vaccine that was deployed to the country’s mink population during the pandemic. She knows the industry well.

But when she and her colleagues went to a farm housing foxes and mink last week, the shrieking of the birds that normally surround the barns was gone, so thinned out were their flocks. Dead gulls littered the ground. The usual barking from the foxes was also missing.

“They were in such a bad condition,” Sironen said about the foxes she saw. She said she walked through two shelters, with some 100 meters of cages on both sides. Only a few had a healthy animal left. “Everything else was either dead or dying.”

The research team, decked out in full PPE, was witnessing the toll of the spread of a highly pathogenic avian influenza, H5N1, which has reached nearly every corner of the globe in recent years and decimated untold millions of birds, domestic and wild. But the virus hasn’t been restricted to birds. It is now causing outbreaks among mammals at a scale previously unseen, including in the past month at a number of Finnish fur farms, home to mink, foxes, and raccoon dogs.

“The silence, the obvious suffering of the animals,” said Essi Korhonen, another virus expert who visited the farm. She said she was struggling to find the words to describe what researchers had seen.

Sironen, Korhonen, and their teams are now part of the research response that involves investigating not just how the virus is attacking animals farmed for their fur, and not just how the virus is spreading to and among them, but also to see if it’s changing in ways that would enable it to transmit more effectively among mammals — including people.

In that way, the work going on here at their labs at the University of Helsinki is part of a growing global effort to better track a virus that has pandemic potential. Researchers this week were analyzing tissue from dead animals to determine where in the brain the virus had infiltrated. A field team was due back Thursday, returning with animals for necropsies in the high biosecurity lab, air and environmental samples for testing, and swabs for both diagnosis and sequencing. The scientists were awaiting sequencing results from their first samples, which would show how the virus was evolving.

“How is it mutating? That is the key question,” Sironen said.

The outbreaks — the first of which was reported July 13 and which have now hit at least 24 farms — have also increased the scrutiny on fur operations, particularly mink farms. Some 20 European countries have phased them out largely because of ethical reasons, but some scientists and policymakers are now invoking public health concerns as they call to shut them down, citing the outbreaks of the Covid-causing coronavirus on fur farms during the pandemic and now the second bird flu event in Europe in less than a year, following one on a Spanish mink farm last October.

As it stands now, the H5N1 virus does not infect people easily. But the fear is that uncontrolled spread in animals like mink gives the virus plenty of chances to evolve in ways that could enable it to spill over into people. Already in Finland, a paper from government researchers indicated the virus has spread from mammal to mammal at the farms — and in some cases has picked up mutations indicating an adaptation toward replicating in mammalian cells.

“These farms are a risk that are not very well controlled, and probably cannot be very well controlled,” said Isabella Eckerle, a virologist at the Geneva Centre for Emerging Viral Diseases, referring to how the farms squeeze normally solitary mammals into mass holdings and how they still have contact with birds and people. “We now have two examples, SARS-CoV-2, and avian influenza. I wonder, what else do we need?”

Covid has galvanized efforts to improve pandemic preparedness and vaccine readiness, but fur farms are a pandemic risk that continue to operate in some places, Eckerle said.

Denmark, for example, culled its entire farmed mink population in 2020 amid fears that an outbreak could spawn a SARS-2 variant. But earlier this year, mink farming was allowed to restart, though the industry is a fraction of its pre-pandemic size.

“It’s for a fashion product, it’s not even for food,” Eckerle said.

For now, Finland’s political leaders have not indicated they are thinking of changing fur farm policies.

Sironen does not take a public position on the farms. What matters to her is that, if they are allowed to operate, she be allowed to keep up her work with them, which, prior to the pandemic, focused on the other infections that affect the animals. But she did say the farms need to improve biosecurity if they continue. On some farms, the shelters holding the mammals’ cages are open on the sides, giving easy entry to birds, which are drawn by the animals’ feed.

Other researchers agree. In the paper published last week, Finnish veterinary and health authorities wrote, “It is clear that current conditions on the majority of farms cannot prevent bird access and much more rigorous biosecurity measures would have to be put in place at the industry level to eliminate these risks.”

In an email, Olli-Pekka Nissinen, the communications director for the Finnish Fur Breeders’ Association, known as FIFUR, said the trade group counts more than 400 active farms and companies as members, so it was only a small minority that were affected. Nissinen said the group was focused on preventing new cases and protecting animals and farmers, not the calls to ban fur farming. He also noted that the virus has spread to other animals recently as well, including to pet cats.

Finland is the second-largest fur producer in Europe, according to FIFUR, with exports in 2022 valued at roughly $250 million. China is the largest market for Finnish furs.

Trying to predict an H5N1 pandemic is almost like warning about an earthquake. It could very well happen, perhaps next year, or in five years, or who knows when. Or never. People who specialize in this virus have been on alert for the equivalent of a bird-spawned Big One for years, and hints of ominous situations have surfaced going back to 1997. But the peril — including moments when the virus seemed like it was starting to spread from person to person — then receded. To longtime H5N1 watchers, the virus has been a threat, and remains one.

What has changed in recent years is the vast spread of the virus in animals, both geographically and into different species. It’s been killing birds in droves, both those on farms and in the wild. It’s infecting — and sickening — mammals, too. Sea lions in Peru and Chile. Otters in the U.K. Grizzly bears in Montana. Just recently, pet cats in Poland and South Korea. (There have been occasional cases in other mammals over the decades as well, including tigers and leopards in a Thai zoo in 2003 and a stone marten in Germany in 2006.)

But there are particular fears about the virus circulating in minks for at least two reasons. For one, mink are susceptible to both avian and human influenza strains. If both forms infect a single animal at the same time, they can swap stretches of their RNA in a process called reassortment. That could allow H5 to pick up human flu genes in a one-stop shop that might make it better suited to transmitting in people. Past flu pandemics have been seeded through reassortment.

(One thing that’s gone the world’s way as the H5N1 panzootic — that is, pandemic among animals — has spread is that pigs, which have played host to flu reassortment in the past, seem resistant to H5N1, said Tom Peacock, a virologist at Imperial College London.)

The other reason for worries about mink is that they’re thought to be not so different from people, at least from a flu perspective. They’re closely related to ferrets, which are used as a model for humans in flu research because they develop similar symptoms and have similar receptors that flu viruses use to infect human cells. If the virus is given opportunities to spread in mink, it could adapt in ways that allow it to better home in on those flu receptors — and that might mean it’s more likely to infect our species.

“Mink, more so than any other farmed species, pose a risk for the emergence of future disease outbreaks and the evolution of future pandemics,” Peacock and fellow Imperial virologist Wendy Barclay wrote in a PNAS editorial just last month, in which they also argued that governments should “consider the mounting evidence suggesting that fur farming, particularly mink, be eliminated in the interest of pandemic preparedness.”

For now, no people are known to have been infected during the Finnish outbreak. None tested positive after the Spanish mink outbreak either.

If anything, recent shifts in the virus’s genome — the H5N1 clade currently spreading around the world is dubbed 2.3.4.4b — may have actually made the virus less adept at cracking into human cells, even if it’s better at spreading among birds. Worldwide, there have been few reported cases in people in the past several years, and many of the seeming infections were so mild that there is some debate over whether they were true infections or the person just had bits of virus in their nose after an exposure.

H5N1 would need to pick up more than a mutation or two before it could take off among people, scientists think. It might also require changes in several parts of its genome. For one, the virus’ polymerase — the bit that enables the pathogen to make copies of itself once it establishes an infection — would need to be altered to work better in mammalian cells.

The virus would also need to tweak its hemagglutinin, the protein on its surface that locks onto host cells to initiate an infection. That protein on the H5N1 virus is currently better suited to attaching to avian cells than mammalian ones. Other changes to the virus might be necessary as well for it to spark a pandemic.

But scientists fear that if the virus does evolve to circulate among people, there could be drastic consequences. Since 2003, there have been about 870 confirmed human cases. Just over half those cases were fatal, in part because an H5 infection burrows deep into the lungs when it does occur.

The outbreak in Finland has been centered in two regions in the country’s west, where most fur farms are located and where wild birds like black headed gulls have tested positive for H5N1. The farms vary widely in size, with some having several hundred animals and some having 50,000.

Most of the 24 farms that have declared outbreaks house foxes, while some have mink or raccoon dogs. Foxes seem to be more vulnerable than mink, researchers say, and the different species seem to be displaying different symptoms, which include both respiratory problems and neurological complications like tremors.

The Finnish Food Authority announced last week that all mink on farms with confirmed infections would be culled, while the euthanizing of foxes and raccoon dogs would be made on a case-by-case basis. “Mink is an especially problematic species when it comes to avian influenza infections,” the agency said.

It’s thought that the virus reached the farmed animals via direct exposure with birds, but there are signs that onward spread within the farms has also occurred, according to the analysis from Finnish government researchers published in Eurosurveillance last week. There were similar clues of mink-to-mink transmission in the Spanish outbreak, including the fact that the animals got sick at different times — indicating it wasn’t just one exposure to an infected bird.

But the routes of that mammal-to-mammal transmission aren’t clear, something that Sironen and other scientists are urgently trying to figure out. Researchers are also testing seemingly healthy animals to see if asymptomatic infections — and asymptomatic transmission — could be occurring.

“We think there is some transmission among the animals,” said Mika Salminen of the Finnish Institute for Health and Welfare, an author of the Eurosurveillance report. “But how widespread is it? Is it through respiratory? Is it through feces?”

Salminen and his colleagues also uncovered in a few of their samples mutations that signaled the virus was adapting to its new hosts, including some in the polymerase that are known to improve the virus’s replicating ability in mammalian cells.

There are still plenty of questions as researchers track the fur farm outbreaks. If the virus seems to be spreading among mink — and they’re thought to have flu receptors similar to those on our cells — why is the virus not so adept at causing human infections? Does it have to do with where the mink have the receptors in their respiratory tracts? Does that just mean they’re exposed to incredibly high doses of the virus in their close quarters? Or maybe their receptors aren’t so similar to ours?

As concerned as they are about the pandemic potential of H5N1, scientists stress that whatever risk the virus may eventually pose to people, it’s already a real threat to animals, causing mass death particularly in birds. Sironen said that because of limited surveillance, it’s not even clear just how many species of wild bird the virus is killing.

“Even if this never becomes a pandemic of people, it is a horrible disease for the animals,” Sironen said.