Inside the global hunt to identify mutations that might lead to more lethal variants.
The questions driving the researchers goes far beyond pet welfare. They’re investigating whether animals infected with the coronavirus might become reservoirs for the evolution of new variants that might jump back into humans — an issue with huge implications for both human and animal health.
In year three of the pandemic, scientists have confirmed that the virus believed to have first spilled over to humans from bats or possibly pangolins has already spread to at least 20 other animal species, including big cats, ferrets, North American white-tailed deer and great apes. To date, incidents of animals infecting humans are rare. Only three species — hamsters in Hong Kong, mink in the Netherlands and, possibly, also white-tailed deer in the United States and Canada — have transmitted a mutated, albeit mostly benign, version of the virus back to humans. But those cases are spurring concern.
The search for infected animals in Texas — led by Texas A&M University in conjunction with the U.S. Centers for Disease Control and Prevention — is part of a scattered but growing global effort to monitor pets, livestock and wildlife for new, potentially more dangerous coronavirus variants and stop them from wreaking havoc on humans.
The World Health Organization warned in March that animal reservoirs could lead to “potential acceleration of virus evolution” and new variants. The agency noted the large numbers of infected animals, and it urged countries to increase their monitoring of mammalian species for SARS-CoV-2 and suspend the sale of live, wild mammals in food markets as an emergency measure. The CDC this year also endorsed efforts to track the virus in animals, even as it described the risk of transmission to humans as “low.”
In March, a city in China ordered the killing of pets whose owners had tested positive, but the action was put on hold after a public outcry. (There was no evidence these pets were spreading the virus.) Earlier this year, Hong Kong’s first outbreak in months is believed to have been caused by hamsters imported from Europe.
Meanwhile, U.S. scientists estimated late last year that a third of white-tailed deer in several states appear to carry antibodies to the coronavirus, suggesting recent infection, and three snow leopards at the Lincoln Children’s Zoo in Nebraska died of covid-19. In 2020, Denmark had culled millions of mink after they were infected and the virus spilled back into humans.
Most new variants are simply scientific curiosities, and they die out. The challenge for scientists is to create a system to identify the dangerous ones — the ones that are more transmissible, more deadly or more likely to break through vaccines — and attempt to halt their transmission.
“We need to be very aware there are going to be more epidemics and pandemics and plan ahead,” said Pamela Bjorkman, a professor at the California Institute of Technology.
In the span of more than two years, the coronavirus itself has been evolving faster than most anyone expected — creating an evolutionary “super-tree” with major new branches seeming to sprout every few months. The environment in which these variants are forming, researchers surmise, is likely one that allows the virus to live longer and thereby make more copies of itself, increasing the prospect of new mutations.
One leading theory is immunocompromised patients, such as those with cancer or HIV, who can harbor the infection for many weeks or months, as compared with mere days for most people. But another more daunting possibility is that the virus is finding hosts among the more than 1 million animal species, many still not catalogued, that inhabit Earth.
“It’s a scary thing.” Bjorkman, who has been working on a universal coronavirus vaccine, said there has long been viral transmission between humans and animals that nobody pays attention to.
The problem is that “every once in a while, there is transmission that catches on” and will explode if it spills into the human population, she said.
Scientists believe most major outbreaks of disease serious enough to be deemed epidemics or pandemics have begun with animals.
H5N1, a highly pathogenic flu that occurs in wild birds, sent fear through the medical community after a young boy died of it in Hong Kong in May 1997. (The first U.S. case was reported in Colorado in April.) SARS1, which caused an outbreak in Asia from 2002 to 2004, infecting more than 8,000 people, is believed to have jumped from civets, a catlike mammal, to humans.
The H1N1 influenza virus that hit the world in 2009 and is estimated to have infected as many as 1.4 billion people is believed to be what scientists call a “reassortment” of flu that has been found in birds, pigs and humans. The MERS virus, first reported in Saudi Arabia in 2012 with a fatality rate as high as 35 percent, is believed to have emerged from camels.
SARS-CoV-2, the pathogen terrorizing the world since early 2020, has higher potential for transmission to animals than many other known viruses because it invades the body by latching onto a receptor known as ACE2, which is found in a number of species. In recent weeks, researchers reported evidence to support early suspicions that the original coronavirus that jumped into humans sometime before January 2020 may have come from wet market animals, perhaps bats, perhaps raccoon dogs, or another animal used for food or fur in Wuhan, China.
As of April, scientists had logged 675 coronavirus outbreaks in animals, affecting 23 species in 36 countries, and other species have been shown to be vulnerable in lab experiments. But there are likely many thousands more that are susceptible. A University of California at Davis study of the potential vulnerability of different species to coronavirus infection — based on modeling of which ones had ACE2 cellular receptors similar to those in humans, because that’s how the virus enters the body — ranked animals as diverse as giant anteaters and bottlenose dolphins as high risk, and Siberian tigers, sheep and cattle as medium risk.
So far, most of the coronavirus transmission appears to have jumped from humans to animals. Scientists have documented infection going in the other direction only three times: from mink to humans, hamsters to humans, and one likely case of deer to humans. None of those three events is believed to have introduced dangerous variants.
In its monthly situation report in late April, the World Organization for Animal Health said that although the main driver of international viral spread is still human-to-human transmission, animal cases “continue to rise.” The big question is not whether certain animals can be infected, researchers say. It is which might act as so-called reservoirs that can serve as sources of new variants that could pose greater threats to humans.
Leo Poon recalled feeling immediately uneasy in January when he got word of a new coronavirus infection in the northern part of the island.
Hong Kong had been quiet for months, and the delta wave that had devastated much of the world seemed to wash over the city with few cases. The city had implemented a strict — some it called draconian — “zero covid” policy that had kept the islands infection-free for long periods. Poon, head of the division of public health laboratory science at the University of Hong Kong, had been helping the government sequence SARS-CoV-2 samples from patients to find out where infections originated and which close contacts were at risk.
This new patient was a 23-year-old saleswoman with mild symptoms of headache and fever who had not had contact with anyone with an infection. Nor had she traveled or been in contact with anyone who had. When Poon checked the global databank that scientists are using to track the evolution of the virus, he was surprised to find that some of the genetic mutations in the young woman’s sample appeared to be novel and had never been documented in any other human sample.
As he delved into the case report, Poon noticed the woman worked at a pet shop, and that’s when it hit him: Could she have gotten covid from an animal?
A flurry of hurried phone calls and emails followed, and Hong Kong authorities locked down the store, Little Boss in the shopping district of Causeway Bay, and a related warehouse, swabbing the nearly 200 animals they found.
“We really have to highlight the concept of one health. It’s not only about human health. We have to consider health in animals and the environment. And if you don’t look after these areas, we are the one that suffer at the end.”
— Leo Poon, head of the division of public health laboratory science at the University of Hong Kong
The rabbits, chinchillas and guinea pigs were cleared. But 11 of the hamsters, specifically the golden Syrian hamsters, tested positive for coronavirus, with a variant similar to the one that had infected the woman. The timelines matched: The hamsters had been flown in from the Netherlands on Jan. 7. The woman became ill on Jan. 11.
The young woman, and a second patient believed to have gotten sick directly from a hamster whose case was described in a preprint paper in the Lancet, did not get very ill. But Poon worried that one of the major changes to the virus related to how it attaches to receptors. He feared that if it was allowed to hop back and forth between humans and animals, it might ultimately change into something less benign.
Investigators identified 150 people, mostly customers who had visited the store, who were at risk of being infected and ordered them into quarantine, banned the importation of small mammals, and put to sleep the remaining 2,000 hamsters in city pet stores within days of the discovery of the link. Public health officials “strongly advised” pet owners to turn over any additional hamsters to be euthanized.
“We really have to highlight the concept of one health,” Poon reflected. “It’s not only about human health. We have to consider health in animals and the environment. And if you don’t look after these areas, we are the one that suffer at the end.”
The first white-tailed deer were tested on a whim.
It was early 2020, and Andrew Bowman, an associate professor of veterinary medicine at Ohio State University, was tracking the animals near Columbus for other purposes and thought he might as well add in one more test. When the results came back positive, he was so taken aback that he rechecked and then triple-checked, and then called in the U.S. Department of Agriculture to verify before announcing the finding to the world.
“At that point, it was a surprise,” he recalled. “But when we step back, we really shouldn’t have been that surprised.”
As suburban communities expand into what was once forest, the population of white-tailed deer living in proximity to humans is increasing. While few people interact directly with deer, scientists are investigating whether the animals might be exposed to the coronavirus through discarded face masks and other trash, contaminated water or, perhaps, some intermediary species. Several scientific teams confirmed the breadth of the cases in deer and found that most of the animals appeared to be asymptomatic.
In August, the USDA announced that its own analysis found antibodies in about one-third of deer in Illinois, Michigan, New York and Pennsylvania. It issued a warning to the public to be cautious in their interactions, and to limit contact between wildlife and domestic animals.
In Canada, Brad Pickering, an animal pathogens expert with the country’s Food Inspection Agency, went further to learn more about the evolution of the virus in deer. Examining samples of 300 animals hunted in Ontario from Nov. 1 to Dec. 31, he was shocked to find 76 mutations in some deer strains.
“That’s a lot, more than omicron,” he said of the number of mutations. “It is showing there seems to be some adaptation to deer or wildlife, in general.”
According to a preprint paper he and a group of more than 30 scientists posted in February, the closest known branches to the deer strain were found in humans in Michigan a year earlier. Those, in turn, were related to mink samples from Michigan previously identified in September/October 2020. Given that the area where the deer samples were taken in southwestern Ontario is adjacent to Michigan, the researchers wondered whether the variant had jumped from humans to mink and then to deer.
“Even if it’s left the human population. It doesn’t mean we’re done with it.”
— Brad Pickering, animal pathogens expert with the country’s Food Inspection Agency
Even more odd, the researchers identified a human sample from the region that was very similar to the highly mutated deer sample. It turned out that person had had close contact with deer, and while the information could not conclusively point to deer-to-human transmission, the evidence was strong.
Neither Bowman nor Pickering worries that the new deer strains of coronavirus pose any immediate danger to humans. Bowman said that the threat is “more of a long-game question.” If “it evolves in a different trajectory than humans, how long do we have before it’s diverse enough that the next pandemic strain spills back into humans?”
“Even if it’s left the human population,” Pickering said, “it doesn’t mean we’re done with it.”
Sarah Hamer’s work at Texas A&M University involves the broad ecology of animals and humans. The future of coronavirus variants, she explained, depends not just on how we interact with a single animal species but also on the web of associations among humans, domestic animals and wildlife.
For cats and dogs, scientists are somewhat confident the transmission has been mostly one-way, from humans to the animals spurred by people snuggling and playing with their pets. Hamer’s research aims to clarify details about the chain of transmission — who brought the infection into the household, who got it next and so forth.
Figuring out what is going on with deer has been much more challenging.
“We cannot explain it as spillover from humans, because not all of them have had a close contact,” Hamer explained. “That’s where it gets pretty interesting to think about.”
On the same weekend that Hamer and Auckland were taking samples from Oreo, Duke, Ellie and their human owners, another team from the same lab was in a nearby forest in eastern Texas, studying small and medium mammals.
After setting a couple of hundred traps that evening, they returned the next morning to find wild mice, wild rats and other mammals. While the primary purpose of the study was to look at vector-borne pathogens such as tick diseases, all the animals were also swabbed for coronavirus before being released back into the woods. The wildlife samples are being stored in a freezer, as Hamer awaits funding to test them.
Right now, such efforts are being conducted mostly piecemeal, often added to non-covid work that is already funded. She and other scientists say a more coordinated global surveillance approach that will target a range of species during different seasons and in different geographic areas is needed to stop a potential new generation of variants.
“There is so much more that should be done,” she said.