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What’s the deal with mink Covid?

In the past year, millions of the animals have been culled to stop the spread of COVID-19 on mink farms across Europe. But this is more than just a fur coat crisis.

ByAlissa GreenbergNOVA NextNOVA Next
Mink_Hero.jpg

Image Credit: Gallinago_media, Shutterstock

Just like humans, mink with COVID-19 are sluggish and lethargic. Their little noses get stuffy. They wheeze and struggle to breathe. And then, unfortunately, sometimes they die.

The pandemic mink problem started slowly: In April 2020, there were reports of mink on farms in the Netherlands falling ill with COVID-19, having caught the virus from their handlers. Then more workers on those farms got sick. And soon, mink and humans across the mink-raising world were infected, with serious outbreaks from Utah to Denmark.

As was so often the case in 2020, things started to get weird over the summer. And by fall, faced with a growing threat of the virus “spilling” from the mink back to humans, Denmark killed millions of its mink.

A few weeks after that, reports of mink corpses rising en masse from their graves started to, well, surface, as the bodies were buoyed by gasses released during decomposition.

And then in December came the news those mink corpses may have contaminated Danish drinking water as their juices seeped into the ground.

Considering the outlandish 2020-ness of it all, it’s hard to know where to land on the scale of doomsday alarm that runs from murder hornets (freaky but not really a threat for now) to the day the sun didn’t come up in San Francisco (a truly frightening sign of things to come). OK, so mink can get COVID-19. What happens when they do, and why does it seem like they get it more than other animals? How do you test a mink for COVID? And, zombie mink apocalypse aside, is this a worthy cause for our already-pretty-much-maxed-out capacity to worry about new things?  

First of all, there’s still a mink industry?

If you’re like me, your first mink COVID thought is: It’s not 1950 anymore; full-length fur coats are no longer de rigueur. It’s been awhile since PETA made news for dumping red paint on some model’s sable cape. We still have a mink industry?

Actually, yes, and quite a significant one. Mink farmers around the world raise animals mostly for fur but also for mink oil, which is used in some cosmetics. And this is not a small business we’re talking about. In 2013, the global mink market was worth $4.3 billion.

Europe has long been the center of mink farming. The continent produced almost 35 million mink pelts on 4,350 farms across 24 countries in 2018 alone. Denmark is the world's biggest mink producer, with, until recently, 17 million animals—all of which they culled in November. Meanwhile, the U.S. market includes some 275 mink farms in 23 states. Wisconsin, the biggest player, produces about a million pelts a year. Utah, Idaho, Oregon, and Minnesota are close behind. 

All this being said, mink farming was already shifting before the pandemic. Japan and several countries across Europe had all either banned or introduced plans to phase out fur production, motivated in part by ethical concerns. (Meanwhile, China has ramped it up to keep up with domestic demand). Within the last decade, the price for a mink pelt dropped from $90 to $30. And now, the virus has created even bigger trouble for an industry where many animals are housed close together. “They’re packing them in, cage-next-to-cage,” says Ohio State University veterinarian and infectious disease specialist Mike Oglesbee. In a situation like that, mink have an awful lot of trouble social distancing, creating what Oglesbee calls an “ideal situation for an outbreak.”

Yes, mink are more susceptible to COVID-19 than other animals

SARS-CoV-2, the virus that causes COVID-19, goes through the same life cycle as all other viruses. To successfully replicate, it must sneak inside an organism, latch onto and enter one of that organism’s cells, hijack that cell’s machinery to produce copies of itself, then make a run for it, eventually leaving the body entirely to transmit to the next host. There’s still a lot we don’t know about COVID, so there’s really a lot we don’t know about mink COVID. But researchers like Barbara Han, a disease ecologist at the Cary Institute, and João Rodrigues, a computational biologist at Stanford University, are on the case. Han and Rodrigues are working on figuring out why some animals (including mink) seem very susceptible to and often die of COVID, while others (like dogs) can get infected but don’t develop severe symptoms or easily pass on the infection—and still others (like cows and chickens) don’t get infected at all.

Viruses are able to infect more than one species when those species have certain physiological traits in common, often traits that developed over the course of evolution. In this case, the answer seems to lie at least partly in the ACE2 receptors that sit on the surface of mink cells and serve as docking stations when SARS-CoV-2 comes calling.

Virus particle attaching to receptor

An artist rendering of a SARS-CoV-2 virus particle as its spike proteins (red) attach to ACE2 receptors (dark blue) on a human cell. Image Credit: Desiree Ho for the Innovative Genomics Institute

ACE2 stands for “angiotensin-converting enzyme 2,” and in humans it’s a protein that, among other things, helps regulate blood pressure. (You may have heard of ACE inhibitor medications that do exactly that.) But ACE2 is extremely common in vertebrate animals in general, Han says, “everything from whales to people, lizards, fish,” since it developed very early on in evolution. That also makes lots of animals at least possibly susceptible to SARS-CoV-2. “In terms of the worst possible receptor for us and the best possible receptor for the virus, ACE2 is a pretty good one,” she says.

After a SARS-CoV-2 viral particle (or virion) pulls up to an ACE2 receptor, a lot of different factors need to line up for the next step—the cell agreeing to let the virus in, or “confirmation”—to happen. Since the first mink outbreaks last summer, Han, Rodrigues, and a team of colleagues have been investigating that process, hypothesizing that how quickly it happens (and whether it can happen at all) is based on how tightly the virion bonds with ACE2 in that moment.

Because ACE2 is a receptor that’s been on the evolutionary rollercoaster for a long time, it’s changed a bit over the eons, and different animals’ ACE2 have different combinations of amino acids in the small portion of the receptor that touches the virus. Since each amino acid is a protein that is crimped into a different shape, the overall shape of that area is slightly different as well.

Han and Rodrigues hypothesize that these differing shapes affect how tight the bond is between the virion and the cell. A tighter fit, they argue, makes an animal more likely to be susceptible to SARS-CoV-2. A looser bond makes it less likely, kind of like opening a lock with a key that’s been poorly cut versus a perfect copy. “The stronger the bond is, the longer the proteins stay bound together,” Rodrigues says. That provides extra time for the confirmation process to finish. According to his analysis, mink ACE2 is at least as good a fit as human ACE2 with SARS-CoV-2—and maybe better.

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It’s hard to tell if the mink industry will survive the pandemic, but it’s at least a moment of reckoning, especially because farming infrastructure is a major part of the problem. Mink aren’t just more susceptible to COVID-19 on a molecular level; they also get sick more than other animals because of their environment. “An organism can be the most susceptible in the world but live just in the Antarctic, and it’s not going to catch COVID,” Rodrigues says. He sees mink getting sick with COVID as a “perfect storm” situation, since “they are very susceptible, and we just happen to farm them in these very high density farms.” Put that way, he adds, it becomes clear how lucky we are that animals we rely on as part of our food supply aren’t equally susceptible and being culled by the millions, “or we’d have a much more serious crisis on our hands.”

How do you even know a mink has COVID?

Farmers can tell a mink is sick because she develops a dry cough and sits around all day watching reruns of “The Office.” Just kidding—sort of. Mink do exhibit COVID-19 symptoms that are very similar to ours: lethargy, wheezing, stomach upset. And they get tested just like us, too. Oglesbee says there’s no organized COVID mink surveillance program, but his best guess is that mink farms are testing with both nasal and rectal swabs. (Apparently the less pleasant of those two is much more effective when it comes to COVID PCR tests.) Some farms may focus on wastewater runoff, like the National Parks Service has taken to doing in Yosemite and elsewhere. But, he says, it seems like most rely on diagnoses drawn from animals that have died and are being tested post-mortem. 

Despite the culls in Europe, Oglesbee said he’s been surprised to see that farms in the U.S. aren’t doing much culling at all. “I was like, ‘OK, so what do you guys do?’” he says. In fact, on at least one farm, mink dying from COVID-19 were still being processed for their pelts, and the end-of-year harvest went ahead undisrupted. That doesn’t affect the people buying the furs, he points out, “but certainly the staff who’re doing the processing would need to be using appropriate PPE.” (Wisconsin is also going so far as to put its mink workers on vaccine priority lists as its rollout moves forward.)

Mink in cage

The combination of mink's susceptibility to COVID-19 and their being kept in high-density living conditions on farms made for a "perfect storm" of virus spread, says computational biologist João Rodrigues. Image Credit: Nettverk for dyrs frihet, Flickr

If American mink farms aren’t going to shut down, the first line of defense against viruses on farms is biosecurity, Oglesbee says. From what he’s seen so far, recommendations around mink COVID have been pretty basic: restrict access to people and animals, keep symptomatic staff at home. He stresses that he doesn’t know how most mink farms are set up but that the most important thing would be containment—dividing the animals up into smaller housing facilities and keeping workers on different units from interacting with each other.

The alternative would be to come up with some kind of mink vaccination plan, which may sound ridiculous, but is actually not unheard of. In fact, one such vaccine is already in development in Finland. But administering intramuscular vaccines like the ones people are receiving across the country is expensive and labor-intensive, so a mink vaccine would probably need to come in oral or aerosol form, Oglesbee says. Han points to past primate vaccination strategies, which took advantage of the animals’ social structure by vaccinating the alpha and making the vaccine transmissible, and to bat vaccines spread in a paste on one individual and then passed throughout the group when the bats groom each other.

So what? Is this a big deal?

As Rodrigues points out, the stakes when it comes to the spread of viral illness in a farmed animal could be much higher. COVID-19 in mink “just means some won't get their gloves,” he says. His true concern lies elsewhere: cross-species transmission.

“Once a disease is established in an animal population, it’s very hard to control it,” Han says, adding that she can’t name a disease we’ve been able to eradicate once it reaches that point. A future where scientists are playing whack-a-mink with these and potentially other species sickened by COVID-19—plus a vaccine that both doesn’t confer 100% immunity and isn’t accepted by 100% of the population—is a difficult one indeed.

Plus, any opportunity for a virus to evolve to fit a different environment presents an inherent risk because it could end up changing that virus in a dangerous way, making it more infectious, more deadly, or more able to jump from one species to another—like, for example, the variants that have emerged recently in the U.K., California, and elsewhere. “Once you introduce a different species that [the virus] can very easily jump to and spread in, as it has in minks, you’re giving it a different environment to adapt to, which triggers a different sort of evolutionary route,” Rodrigues says.

“The danger in having multiple animal hosts is you’re adding more players to the evolution games.”

That means the virus might adapt in ways that it wouldn’t inside the human body. “The danger in having multiple animal hosts is you’re adding more players to the evolution games,” he says. And yes, one of the risks of spillback—the virus traveling from humans to animals, then back to humans—is that a virus could change enough to “escape” our existing vaccines. That the mutated variants of SARS-CoV-2 coming out of mink farms seem to be mostly neutral thus far is pure luck, he says. 

In fact, Oglesbee’s major concern about mink COVID is actually not about the mink, or even about COVID. In his work leading OSU’s Infectious Diseases Institute, he and his colleagues have launched a wild animal surveillance program watching for infection in species like the deer mouse, which is ubiquitous in North America and has been shown to be susceptible to SARS-CoV-2. 

Some 60% of emergent viruses come from animal populations, he points out, so this is not just a hypothetical concern. A mink reservoir for COVID-19 could, down the road, give rise to an entirely different novel virus that sparks a pandemic. “Keep in mind this is the third coronavirus pandemic in the past 20 years,” he says, referring to SARS in 2003 and MERS in 2012. “That’s the ‘holy cow’ issue.” 

Wait, but what about other animals!?

Oglesbee says he isn't trying to keep anyone up at night but does want to highlight the importance of animal surveillance when it comes to managing, or even preventing, a pandemic—an area of research that’s often underfunded. “People don’t want to fund something that may or may not happen in the next 20 years,” he says, pointing to the human tendency to treat problems reactively, rather than proactively. “We don’t look for it, we don’t find it, therefore it doesn’t exist. And when the problem smacks us in the face we’re like, ‘Oh my god, where did that come from?’” 

Oglesbee, Han, and Rodrigues all say that mink culls and stricter biosecurity are a good preliminary step. But that doesn’t amount to much if we don’t take other non-mink spillover threats seriously too. As of yet, “we don’t have a plan, and that’s crazy,” Han says. “But it’s not that we can’t think of a plan.”

For Oglesbee, that plan starts with stepped-up virus surveillance. There’s already fairly routine monitoring of populations like county-fair pigs for porcine flu, he points out. “Why can’t we expand that?”—both beyond that flu and beyond those pigs? We need, he argues, to figure out how to see our next possible pandemic coming much sooner. 

The result: a list of potentially susceptible animals who seem most likely to come down with COVID-19 and pass it back to humans, including pets like gerbils and guinea pigs, farmed animals like water buffalo and red fox, and two kinds of common lab mice. 

Han, Rodrigues, and their colleagues are trying to expand surveillance in another way. In a preprint (not-yet-peer-reviewed) study released in February, they modeled the strength of the bond between SARS-CoV-2 and ACE2 in several hundred animal species for which an ACE2 DNA sequence is already available. Then, they trained an algorithm to recognize more general features of animals with potentially strong virus-ACE2 bonds and cross-referenced the species it identified with maps of where those species live in close proximity with humans. The result: a list of potentially susceptible animals who seem most likely to come down with COVID-19 and pass it back to humans, including pets like gerbils and guinea pigs, farmed animals like water buffalo and red fox, and two kinds of common lab mice. 

Research suggests SARS-CoV-2 diverged from a bat virus about 40 years ago, but it lacked the “opportunity to contact a human in a high enough dose to cause an infection,” Han says. But with humans increasingly moving into previously wild spaces, the kinds of contact necessary for that dose are more and more frequent. And, she notes, that same dynamic could still put other vulnerable species at risk of COVID-19—like orangutans, whose ACE2 is virtually indistinguishable from ours, and mountain gorillas, which experience high levels of human interaction in the form of ecotourism

Han says the solution here is working around scientific research’s inherent siloes to form a “brain trust” that gets molecular virologists (who know viral genomes), ecologists (who know environmental factors), and museum curators (who have access to huge collections of animal specimens) talking to each other. “We don’t have a plan of action, but there are lots of people with lots of ideas,” she adds. “It might seem like an insurmountable problem, but it’s not insurmountable.”

Oglesbee agrees, which is why his team at OSU’s Infectious Diseases Institute is concentrating on putting into place the kind cross-discipline relationships and animal surveillance programs necessary to fight the next pandemic. “If you’re only concerned about human health, you need to understand that the solutions lie in disciplines in environmental sciences, microbiology, and vet medicine,” he says. “This issue of interdisciplinary approaches isn’t just something cool, it’s essential.”

Due to a reporting error, we have corrected a quote from João Rodrigues. It says COVID-19 in mink “just means some won't get their gloves.”

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