When several tigers and African lions at the Bronx Zoo tested positive for the coronavirus last April, Tracey McNamara was not surprised.
The big cats fell ill a little more than a month after New York City reported its first Covid-19 case. But McNamara, a veterinary pathologist at Western University of Health Sciences in Pomona, California, knew as early as January 2020 that zoo animals might be at risk: A senior Chinese health official had warned the public that the virus spread between mammals and that they should quarantine any pets that might have encountered an infected person.
Soon after the virus infected the zoo’s felids, Chinese scientists reported in the journal Science that cats were “highly susceptible” to the coronavirus. SARS-CoV-2 (short for severe acute respiratory syndrome coronavirus 2), the virus that causes Covid-19, “can replicate efficiently in cats,” the authors wrote. And, perhaps more importantly, they noted, the virus can transmit “between cats via the airborne route.”
The pandemic has claimed more than 2 million human lives worldwide, more than 418,000 of them in the United States, even as governments spend billions to contain it. And now an expanding list of species have contracted Covid-19, including lions, tigers and gorillas in zoos, mink on farms and in the wild, and pet dogs and cats. Studies show that other animals can be infected in the lab, including ferrets, hamsters, rabbits, mice, monkeys and raccoon dogs.
Scientists like McNamara say there’s an increasingly urgent need to figure out which animals can not only contract but also transmit the virus. It’s clear that small carnivores like mink, raccoon dogs and cats do so, though so far only mink have infected people. But if enough animals become reservoirs of infection, and allow the virus to move easily between animals and people, it will be much harder to control the pandemic.
Dedicated efforts to monitor captive and wild animals that could be susceptible are essential, said Christine Kreuder Johnson, director of the EpiCenter for Disease Dynamics at the University of California, Davis One Health Institute. Otherwise, they could become sources of transmission after the outbreak is controlled in people.
Over the past few decades, international health agencies have recognized that controlling infectious diseases requires focusing on the interconnections between people, animals and their environment. With this “One Health” approach, explained Ann Hohenhaus, staff veterinarian and hospital spokesperson for the Animal Medical Center in New York City, “if you have a problem in one, you’re going to cause problems in the others.”
Covid-19, she added, is “a horrifyingly excellent example” of that.
The novel coronavirus revealed the folly of ignoring a One Health approach, Johnson and her colleagues argued in a commentary published in Health Affairs last week, calling the U.S. response “unprepared, overconfident and inept.” They urged the incoming Biden administration to create an interagency One Health task force to improve U.S. pandemic preparedness by forging domestic and global collaborations that target “key drivers of disease emergence, including climate and global environmental changes.”
It’s a massive undertaking. But with zoonoses—pathogenic diseases that spill over from animals to humans—accounting for three-quarters of emerging infectious diseases, it’s one that public health officials cannot afford to ignore. At the least, it will require better coordination between public and animal health agencies. Ideally, McNamara and others say, it would involve launching a comprehensive animal and environmental health surveillance network.
McNamara has urged public health officials to do both ever since the West Nile virus caused scores of crows to drop dead around the grounds of the Bronx Zoo more than two decades ago, when she was the zoo’s lead pathologist.
In the summer of 1999, McNamara feared she was seeing something new to veterinary medicine when wild crows, and then flamingos and other birds at the zoo, started keeling over. Around the same time, city health officials reported an unusual cluster of cases and deaths associated with a strange encephalitis, or brain inflammation, after a record-breaking heatwave and torrential rains—perfect breeding conditions for mosquitoes. McNamara’s gut told her the animal and human illnesses were linked. She shared her concerns with the Centers for Disease Control and Prevention, but officials there told her they saw no connection between dying New Yorkers and birds. The CDC dealt with human health, she was told, not flamingos. That “jurisdictional straitjacket,” she argued in a 2018 Ted talk, blinded officials to a novel public health threat.
It took several weeks and misdiagnoses at state and federal labs before scientists finally identified the culprit as West Nile, a mosquito-borne disease previously unknown in the Western Hemisphere. The bungled approach to the outbreak inspired a congressional report on lessons for public health preparedness. The report stressed recognizing that many emerging diseases affect both animals and people, and the importance of bolstering the links between public and animal health agencies to prevent future spillovers.
More than two decades later, however, nothing has changed, McNamara said, even though yawning gaps in surveillance have opened the door to several new deadly viruses. And even though SARS-CoV-2, like West Nile, jumped from animals to people, she added, “all anybody wanted to look at was people.”
All the species in closest contact with humans in crowded urban centers—dogs, cats, zoo species, shelter animals, non-game wildlife—still do not fall under the jurisdiction of any federal agency and are not under surveillance, she said.
So instead of catching potential threats to human health in animals, she added, “the only time we find stuff is when we have dead people.”
Missed Surveillance Opportunities
Bats host many different coronaviruses, and SARS-CoV-2, like the first deadly SARS virus to emerge nearly 20 years ago, is likely to have originated in bats. Despite theories that it escaped from a lab in Wuhan, China, most scientists believe the virus evolved in a bat and then somehow acquired the ability and opportunity to infect people. Of the seven coronaviruses known to infect humans, four typically cause the common cold. It wasn’t until outbreaks of severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012 that coronaviruses started killing people.
Researchers traced the original SARS virus to masked palm civets in live animal markets, and later found it in bats. Genetic analysis suggests that it jumped from bats to civets (commonly called civet cats, though they’re more weasel than cat) before infecting humans.
“Within civets, the virus acquired just a couple mutations that enabled it to use the human receptor,” said Cody Warren, a virologist at the multidisciplinary BioFrontiers Institute at the University of Colorado, Boulder. “It’s almost like the civet cat was a mixing vessel that allowed for this jackpot set of mutations that then enabled the virus to jump into humans.”
Scientists still don’t know exactly which genetic changes allowed the novel coronavirus to jump from animals to people or to infect different species. But identifying an intermediate host, or a more closely related bat virus, Warren said, would go a long way toward solving the mystery.
Like the original SARS, SARS-CoV-2 hijacks proteins called ACE2 receptors on the surface of cells found in people and other mammals. It seems to have found a perfect reservoir in people, Warren said, because it can spread without killing most of its hosts and even without making people sick. “It’s pretty exceptional in terms of its ability to transmit and not cause overt disease,” Warren said.
And a recent study in PLOS Biology shows that the virus has the ability to infect a broad range of ACE2 receptors in mammals, which the authors warn “confirms the potential risk of infection to a wide range of companion animals, livestock, and wildlife.” Veterinarians have been discouraged from routinely testing animals for Covid-19 to save scarce resources for people. That recommendation has not changed since the start of the pandemic, even though last spring Chinese researchers reported preliminary evidence that the virus can efficiently replicate in cats, cause severe disease in young cats and spread via droplets to other cats.
McNamara first raised concerns about the need to test companion animals in February, as part of the “Red Dawn” team of government and academic health experts who were monitoring the pandemic. A few months later, she approached the Department of Homeland Security for testing support.
“I begged for $300,000 to do transmission studies,” she told me. “It kills me to even talk about transmission studies (with pets), but we’re talking about a novel zoonotic potentially pandemic threat, and people sleep with their dogs and cats.”
But McNamara said she could not find federal funding to do the studies. The evidence so far indicates that dogs are not as susceptible as cats. Experts feared that cats might not show obvious symptoms and could serve as a silent intermediate host, but no case of cats passing the virus to people has been reported so far.
Most infections in animals are caught when they show symptoms and are in close contact with someone who’s tested positive. It’s still not clear whether, like people, many animals who have been infected have no symptoms, Warren said. “When we’re catching these infections in animals, is it just the tip of the iceberg?”
McNamara said she’s now seeing the same reluctance to test pets and other animals that people encounter every day as she did during the West Nile outbreak. After Chinese researchers established that cats in Wuhan tested positive for the coronavirus, it raised several important questions, she said. “How much virus do they exhale? How do they shed the virus? What routes of transmission might there be? Do they shed sufficient virus to infect a human being?”
All those questions, McNamara said, should have been answered a year ago.
But the United States has no infrastructure to mount a coordinated response to a rapidly spreading respiratory pandemic in companion animals, she said. She submitted a proposal to Homeland Security with a colleague to address that gap in 2011. “They basically laughed at us,” McNamara said, adding, “No one’s laughing now.”
Tracking Susceptible Species
The first evidence that mink could contract the new coronavirus and infect people was reported in May by Dutch researchers studying fur farms in the Netherlands. The study, published the following month the journal Eurosurveillance, showed that humans probably infected the mink, which then infected each other. Stray cats near the farms also tested positive.
The cats most likely contracted the virus from the mink, said study coauthor Wim van der Poel, a professor of emerging and zoonotic viruses at Wageningen University, because the cats’ viral RNA closely resembled viral RNA taken from mink in the same location.
The Dutch ended up killing hundreds of thousands of mink and the government announced plans to accelerate plans to ban the country’s fur farms. In November, Denmark culled millions of the animals after an outbreak sparked fears that the virus was establishing a new animal reservoir. So far in the United States, several mink have escaped from fur farms in Oregon, and last month the first infected wild mink was caught near a mink farm outbreak in Utah.
Why mink have proven so susceptible and can infect humans, Warren said, is the “million dollar question.”
Beyond the risk of mink or other animals infecting people, Warren worries that a virus circulating in animals that can infect humans might undergo mutations that allow it to escape a vaccine.
So far, there’s no evidence that the mink mutations will dampen the available vaccines’ effectiveness, though, and researchers are working to ensure that current vaccines protect against the new variants that have emerged.
In January, van der Poel’s group provided additional evidence in a study published in Science that showed mink were the most likely source of human infection. “It is imperative that the fur production and trading sector should not become a reservoir for future spillover,” the authors wrote.
Many of the small carnivores raised for their fur could potentially become reservoirs. Last month researchers reported in the journal Emerging Infectious Diseases that raccoon dogs, bred in China by the millions for their fur, could transmit the coronavirus after being exposed in the lab. The animals, which like civets were considered potential intermediate hosts for the original SARS, could eventually pose a similar threat with the new coronavirus, the authors warned.
It’s becoming clear that many different carnivores are susceptible to the virus, just as they were to the original SARS virus, said Johnson of UC Davis. “There are a lot of lessons to be learned there,” she said.
If the virus proves as contagious in other small carnivores as it is in mink, Johnson said, “there’s going to be widespread distribution in farmed animals as well as in free-ranging wild animals.”
Taking ‘One Health’ Seriously
If we want to understand what’s driving the emergence of novel diseases like Covid-19, McNamara said, we should look in the mirror.
Zoonotic diseases exploit openings created by clear-cutting forests, intensive farming, the exotic animal trade and other human activities that displace wildlife. Deforestation, one of the major causes of habitat loss, also contributes to climate change. And, while there’s no direct evidence that climate change is affecting the coronavirus pandemic, several studies, including a 2019 review of outbreaks following a recent El Niño event, have linked infectious disease outbreaks to climate anomalies that created weather conditions favorable to pathogens.
Rising temperatures have also forced animals to shift their ranges, increasing their likelihood of encountering people. The more species a virus can infect, the better its chances of acquiring mutations that allow it to spread more easily, escape detection, evade vaccines or therapies, cause more severe disease and infect new hosts.
Figuring out which viruses are circulating in wildlife populations is critical, said Johnson, and that requires understanding how animals are affected by human encroachment.
For a study published near the start of the pandemic, Johnson and her colleagues found that spillovers were directly related to human activities that affected animals and their habitat, with bats and primates at greatest risk of harboring zoonotic viruses. “It’s the mammal species that are in decline globally because of exploitation and habitat loss that have shared more viruses with us,” Johnson said.
Human activities—from habitat destruction to hunting and the wildlife trade—have eroded the social distancing between people and wildlife that prevented disease transmission.
For McNamara, the best way to avoid spending trillions of dollars responding to a pandemic is to focus on prevention by closing jurisdictional gaps and investing in cross-species surveillance. “I would hope one of the lessons to be learned here is that the next time we face another novel, zoonotic threat, you need to get some veterinarians in the room.”
Veterinarians already work at the frontier of novel diseases and have access to a rich library of archival biological samples that could help identify species that could drive spillovers.
But the “ultimate in real-time detection,” McNamara said, would be harnessing technology like satellites and climate models that can predict conditions that favor outbreaks before they even infect animals.
“This all happened so fast,” McNamara said, “but it’s not like people weren’t warned.”