Publisher Health

In late September of 2020, captive mink on a farm in Michigan suddenly fell ill. They stopped eating, struggled to breathe and bled from the nose, according to a report from the World Organization for Animal Health. Two thousand animals died.

Laboratory testing soon confirmed that the mink were infected with the coronavirus.

The Centers for Disease Control and Prevention dispatched a team of outbreak investigators, who collaborated with other agencies to swab mink, farm workers and a menagerie of other animals, from rats to raccoons, to determine how the virus had spread.

“We tried to leave no stone unturned,” said Dr. Casey Barton Behravesh, who directs the C.D.C.’s One Health Office.

Last month, the C.D.C. confirmed that four Michigan residents, including two farm employees, had been infected with the same unique coronavirus variant that was found in the mink. It was the first, and so far only, known instance of possible animal-to-human transmission in the United States.

But many questions remain: When, and in whom, did the variant first emerge? How did a taxidermist with no connection to the farm contract it? Could there be a link between the Michigan mink outbreak and a white-tailed deer variant that scientists recently discovered in neighboring Ontario?

“It really feels very much like a puzzle,” said Dr. Samira Mubareka, a virologist at Sunnybrook Research Institute and the University of Toronto. “It’s not just pieces that are missing — it’s contiguous, interlocking pieces that are missing.”

Since the early days of the pandemic, when the coronavirus tore through fur farms, scientists have worried that mink might become a long-term reservoir for the virus and a potential source of new variants.

To date, coronavirus infections have been detected in mink on 18 American farms, the most recent in Wisconsin in February. Even as Congress considers a ban on mink farming, there is still no national system for proactive surveillance on mink farms, which are not required to report cases to federal authorities. And officials have not released much information about the outbreak investigations they have conducted; some of those details are reported here for the first time.

Together, the secrecy and spotty surveillance make it difficult to determine how much of a risk mink farms pose, scientists say. And it threatens to leave experts blind to the emergence of worrisome new variants that could spill back into humans, extending the pandemic.

“Combined with a desperate need for better more systematic surveillance in humans and animals, we could really benefit from increased transparency regarding spillover and spillback risk,” said Vivek Kapur, a veterinary microbiologist at Penn State University.

The investigation

The Netherlands and Denmark were the first countries to report mink farm outbreaks, in the spring and summer of 2020. Scientists pieced together an unsettling chain of events: It appeared that humans had transmitted the virus to mink; that the virus had mutated as it moved among the mink, and that the animals then spread the altered virus back to humans.

“All of that jumping back and forth over the fence is what we saw,” said Dr. Marion Koopmans, a virologist at Erasmus University Medical Center in Rotterdam. “And that’s something that, as a virologist, you don’t really like.”

The Netherlands and Denmark took “quick and decisive” action, said Adriana Diaz, a doctoral student at the University of London who studied these responses. Dutch authorities conducted antibody testing on all farms and required farmers to report respiratory symptoms in mink and regularly submit carcasses for examination. Still, the virus proved difficult to control, and both nations ultimately shuttered their mink farms.

The United States took a different tack, developing a set of voluntary guidelines to help farmers keep the virus at bay, including asking farm workers to wear masks and notifying authorities of suspected cases.

But there was no national screening program and federal officials relied upon farm owners to self-report outbreaks. “All of our federal surveillance efforts are voluntary,” said Dr. Tracey Dutcher, the science and biodefense coordinator for the Animal and Plant Health Inspection Service at the United States Department of Agriculture.

The C.D.C. investigated outbreaks only when officially invited. Some owners of affected farms declined to participate, and field teams only performed on-site investigations on eight farms, Dr. Barton Behravesh said.

On the Michigan farm, C.D.C. investigators worked with the U.S.D.A. and state agencies to test humans and animals for the virus. They collected swabs and samples from 159 mink on the farm; all but two were actively infected, Dr. Barton Behravesh said.

None of the other animals tested around the farm — two dogs, a cat, raccoons, opossums, striped skunks, rats, groundhogs and rabbits — were infected, but one dog tested positive for antibodies, officials said.

Two of the farm’s employees were infected with the same version of the virus that was spreading among the mink. The variant had two mutations that had also been found in farmed mink in Europe and in people connected to mink farms.

Officials found the same mutations in a sample collected from another Michigan resident nearly two months after the mink outbreak and then in a fourth person connected to that resident. The third case was a local taxidermist, according to internal health department emails obtained by the Documenting Covid-19 Project and the Detroit Free Press, and the fourth case was the man’s wife, the organizations later reported. (Michigan’s Department of Health & Human Services declined to confirm these details for privacy reasons.) Neither had any known connection to the mink farm.

Unanswered questions

These findings suggest a likely scenario, experts said: A person passed the virus to the mink, and the mutations emerged as the virus spread among the animals, which then transmitted them back to the farm workers. “We concluded that there was likely mink-to-person spread on this particular Michigan farm,” Dr. Barton Behravesh said.

But determining when, and in whom, the mutations first appeared requires many more virus samples from farm workers, local residents and mink, collected before and after the outbreak. “That data doesn’t exist,” said Arinjay Banerjee, a virologist at the University of Saskatchewan.

Throughout 2020, testing was difficult for Americans to access and few patient samples were being sequenced. Surveillance in animals was even worse; until this spring, federal officials explicitly recommended against routinely testing animals for the virus.

“Widespread testing wasn’t available, then there became a shortage of certain supplies,” Dr. Behravesh said. “So we didn’t want there to be, you know, a mad rush to test animals.”

Without more samples, it’s impossible to rule out the possibility that the variant emerged in humans, who then spread it to mink, scientists said.

A bigger puzzle is how the taxidermist and his wife got it. The most likely possibility, several experts said, is that the variant was circulating more widely in the human population than was known, and the couple caught it from another infected person.

Another, more speculative, possibility is that they picked up the variant from another animal species. “Taxidermists deal with other dead animals,” said Linda Saif, a virologist and immunologist at Ohio State University.

But because the cases were detected “weeks to months” after the two fell ill, testing any animals they may have been in contact with “was either not feasible or not indicated,” said Lynn Sutfin, a spokesperson for the Michigan D.H.H.S.

The pair also had close contact with deer while hunting “on or very near to their own illness onset dates,” according to the health department emails obtained by the Documenting Covid-19 Project and the Free Press.

Studies suggest that humans have repeatedly introduced the virus to white-tailed deer, which then transmit it easily among themselves. People could have passed the mink variant to deer, which might have transmitted it to the taxidermist and his wife. “Given the very high viral burdens that have been noted in white-tailed deer, the spillover to them could certainly have occurred from the deer,” Dr. Kapur said.

Alternately, deer might have picked up the virus directly from infected mink, which have been known to escape from farms. Feral cats on mink farms have also tested positive for the virus and may act as vectors between captive mink and wildlife.

Or deer might come into contact with mink farm waste, Dr. Kapur said. On farms with outbreaks, airborne dust, as well as the straw and hay that the mink bed down on, can be highly contaminated with virus, Dutch researchers found.

Another finding makes a potential deer link intriguing, scientists said. Canadian researchers recently detected a unique coronavirus variant circulating in deer in southwestern Ontario. Although the deer variant was strikingly different from other known variants, the closest matches were viral samples collected from people and mink in Michigan in late 2020.

One possibility, still theoretical, is that whatever version of the virus was circulating among mink and humans made its way into deer, where it evolved into a new variant. “There could be interactions and interspecies transmission that have been cryptic and we haven’t really picked up on ,” said Dr. Mubareka, an author of the Ontario study.

Dr. Banerjee was skeptical that deer played a role in the case of the taxidermist and his wife. “I think that’s just speculation at best,” he said. But he acknowledged that the data are so sparse that many possibilities remain. “Are there other animals we are missing?” he asked.

Missed opportunities

Even the data that exist are not always clear-cut. As part of another investigation in the fall of 2020, the U.S.D.A. tested a dozen cattle on a Wisconsin mink farm with a coronavirus outbreak. Although the cattle tested negative for the virus, three had low levels of antibodies, said Travis Weger, a U.S.D.A. spokesperson.

However, these findings “did not meet the criteria for a positive result,” Mr. Weger said in an email, and could have been triggered by antibodies to other coronaviruses known to infect cattle. Experimental studies suggest that cattle are not susceptible to SARS-CoV-2, he added.

Still, outside experts said that it is difficult to draw conclusions without more analysis — and that the findings suggest a need to monitor livestock, especially as new variants emerge.

Some also expressed concern that officials have not disclosed these and other findings from the mink investigations.

Dr. Barton Behravesh, of the C.D.C., said that the viral sequences obtained during the investigations are available on GISAID, a repository of viral genomes, and that more details would eventually be published in scientific journals.

The U.S.D.A. is using funding from the American Rescue Plan to ramp up animal surveillance and would like to do more active monitoring on mink farms, Dr. Dutcher said: “We’re still working through some of the questions and conversations with industry.”

Although the U.S.D.A has no reports of active outbreaks after 2020, mink infections can be silent. Researchers found antibodies in mink on a Wisconsin farm in February 2022 and on a farm in another, unnamed state in May 2021. There was no evidence of symptomatic outbreaks on either farm, which had supplied samples from healthy animals for research, Mr. Weger said in an email.

But the presence of antibodies suggests that the virus spread on the farms undetected.

“Without surveillance, how would you know?” said Dr. Jim Keen, the director of veterinary sciences at the Center for a Humane Economy, a nonprofit animal welfare organization that supports banning mink farming in the United States.

Some mink herds have now been vaccinated, which might help slow transmission on farms. But vaccination could make infections more likely to be asymptomatic, Dr. Keen said.

The United States should be regularly testing both mink and farm employees, sequencing positive samples and communicating the results in a timely way, Ms. Diaz said.

As new variants emerge, some perhaps capable of infecting new species, ongoing surveillance is needed to understand the “web of transmission that may be going on with wildlife, farmed animals and humans,” Dr. Saif said. “If you don’t look for something, you’re not going to find it.”