We think of COVID-19 as a human pandemic, but it is much more than that. The virus that causes the disease, SARS-CoV-2, can infect a wide and growing range of animals, both captive and wild.
So far, the virus has been detected in more than 100 domestic cats and dogs, as well as captive tigers, lions, gorillas, snow leopards, otters and spotted hyenas, according to the US Department of Agriculture. US zoo staff have recorded a single positive case in a binturong, coati, puma, domestic ferret, fishing cat, bobcat, baboon and squirrel monkey.
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In the United States, only three wild species — mink, mule deer and white-tailed deer — have tested positive, according to the USDA. In other parts of the world, cases have been reported in wild black-tailed tamarins, large hairy armadillos, and a leopard.
But tests in wild animals are rare, and it is likely that COVID-19 has affected many more species, as new research is beginning to show. “I think the spread to wild animals is much greater than previously thought,” says Joseph Hoyt, a disease ecologist at Virginia Tech in the United States.
How does SARS-CoV-2 infect such a wide range of species and what are its implications?
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The connection with the receiver
One of the main reasons lies in a complicated receptor found in all mammals, called ACE-2. This receptor plays an important role in the regulation of blood pressure and other physiological functions.
Once the SARS-CoV-2 spike protein enters the body, it begins to infect host cells by binding to the ACE-2 receptor, which is widespread in the upper respiratory tract and sinuses of humans and many other mammals.
The physical structure of the ACE-2 receptor varies relatively little between vertebrate species compared to other similar proteins, says Craig Wilen, a Yale University virologist. Still, there are enough small variations that scientists initially thought it would be highly unlikely that some mammals would become infected.
But that idea has changed, since the animals that were initially considered less susceptible have shown the opposite. It now appears that many, if not most, mammalian ACE-2 receptors are susceptible and not a limiting factor for the virus.
“It sounds like it’s good enough… even if it’s not a perfect match,” says Rick Bushman, a professor at the University of Pennsylvania School of Medicine who studies host-microbe interactions.
Instead, there are likely many other factors at play that determine vulnerability, the details of which remain almost entirely unknown.
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A broad range
We already know that the virus can infect and spread in wild mink and white-tailed deer, and in both species there is at least one verified case where the virus has passed from humans to animals and back to humans. In addition to mink, pet ferrets and golden hamsters also seem to pick up the virus easily in captivity.
In addition to the animals mentioned, a study published soon in BioRxiv identified probable cases of SARS-CoV-2 infection in wild deer mice, raccoons, opossums, gray squirrels, white-footed mice, and striped skunks, among others.
Carla Finkielstein, a co-author of the paper, along with Hoyt and conservation biologist Amanda Goldberg, were surprised when they first found evidence of SARS-CoV-2 infection in opossums in Virginia, USA.
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“We were worried, because that means it’s jumping” into distantly related mammals, Finkielstein says. “Possums are biologically very different from us,” Goldberg adds.
Opossums are marsupials that give birth to bee-sized young, which suck from the teats of their mother’s pouches. Marsupials diverged from placental mammals (which include many common mammals) more than 150 million years ago.
If SARS-CoV-2 can infect opossums, they reasoned, it likely could infect a huge variety of mammals. In fact, the team found signs of SARS-CoV-2 antibodies in significant percentages of six species of urban wildlife in southwestern Virginia. They also obtained positive PCR results (which are indicative of infection, but do not prove it) in two of these species and four others, including red foxes and lynx.
Another recently presented paper also found evidence that the pathogen infected 17% of the New York sewer rats tested. And a small percentage of Connecticut white-footed wild mice have also been infected, according to research by Rebecca Earnest, a Yale University doctoral student.
(Related: How do diseases spread from animals to people?)
Questions about the infection
But how do wild animals like deer get exposed to the virus?
The question still has no answer, but there are theories. Wild animals could become infected by coming into contact with garbage or human sewage, or by inhaling the virus when they are around people. Exposure could also occur through interaction with domestic animals, such as dogs and cats, or captive deer, which may carry the virus.
But “I think everyone agrees… that nobody knows,” Bushman says.
In whatever way whitetail deer are being exposed, it happens often. A 2021 study suggested that more than a third of deer in the Northeast and Midwestern US had been exposed. Another study found that the virus had entered deer at least four times from humans, and a third study found that the virus had passed to a single human in Canada.
One of the reasons why animal infections are important is because they represent new reservoirs for the virus, where it can stay and acquire new mutations that, in theory, could help it spread better if it returns to humans.
“More transmission among more species is not something we want to see,” Earnest says.
(Related: Which animals suffer from COVID-19 and why)
a forgotten problem
The ability of SARS-CoV-2 to infect wildlife amounts to a hidden panzootic—the animal version of an epidemic—with effects almost entirely unknown, Finkielstein says.
Infected animals usually have mild symptoms, but experts know almost nothing about how different variants of the virus affect most animals. Sometimes the infections are deadly. The virus appears to kill a small percentage of infected mink, and three snow leopards died of COVID-19 complications at the Lincoln, Nebraska, children’s zoo.
Wilen cautions that we don’t really know how sick animals in the wild can get. He cites the example of the chimpanzee simian immunodeficiency virus (SIVcpz), which jumped to humans and became HIV-1. For a long time it was thought that SIV only caused infections in humans. SIV was long thought to cause only mild symptoms in chimpanzees, but research eventually determined that the virus can cause an AIDS-like illness in animals, often shortening their lifespans.
The effects of viruses are especially difficult to study in wild animals, especially at an ecological level, Hoyt adds.
“We don’t know its consequences for wildlife,” Finkielstein agrees. “That’s another aspect that has been largely ignored.”