COVID-19 is more widespread in animals than we thought

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 a hundred domestic cats and dogs, as well as 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, lynx, mandrill and squirrel monkey.

In the United States, only three wild species — mink, mule and white-tailed deer — have tested positive, according to the USDA. Cases have been discovered elsewhere in the world in wild black-tailed marmosets, large hairy armadillos and a leopard.

But wildlife testing is rare, and COVID-19 is likely to have affected many more species, emerging research is beginning to show. “I think the spread in wildlife is much more extensive than previously thought,” says Joseph Hoyt, a disease ecologist at Virginia Tech.

How does SARS-CoV-2 infect such a large range of species and what are the impacts?

Receptor binding

A major reason lies in a complex receptor found in all mammals called ACE-2. This receptor plays an important role in regulating blood pressure and other physiological functions.

Once the spike protein of SARS-CoV-2 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 virologist at Yale University. However, there are enough small variations that scientists initially thought that some mammals would be very unlikely to become infected.

But that opinion has changed as animals originally thought to be less sensitive have proven anything but. It now appears that many, if not most, mammalian ACE-2 receptors are sensitive and do not represent a limiting factor for the virus.

“It looks like it’s a pretty good one … 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 many other factors at play that determine vulnerability, the details of which remain almost entirely unknown.

A wide range

We already know that the virus can infect and spread within wild mink and white-tailed deer—and for both species, there is at least one verified case in which the virus has passed from humans to animals and back to humans. In addition to mink, domestic ferrets and golden hamsters appear to easily spread the virus to each other in captive settings.

In addition to the previously listed animals, a prospective study published ahead of print in BioRxiv identified possible cases of SARS-CoV-2 infection in wild deer mice, raccoons, opossums, gray squirrels, white-footed mice, skunks with lines and more.

Carla Finkielstein, a co-author of the paper, along with Hoyt and conservation biologist Amanda Goldberg, were surprised to find evidence of SARS-CoV-2 infection in Virginia opossums for the first time.

“We were concerned, because that means it’s jumping” to nearby mammals, Finkielstein says. “Opossums are very different from us biologically,” adds Goldberg.

Opossums are marsupials that are born as small as a honey bee, sucking their teats into their mothers’ pouches. Marsupials diverged from placental mammals—which includes many common mammals—more than 150 million years ago.

If SARS-CoV-2 can infect opossums, they reasoned, it is likely that it can infect a massive variety of mammals. Indeed, the team found signs of antibodies against SARS-CoV-2 in significant percentages of six urban wildlife species in southwest Virginia. They also got positive PCR hits — which are indicative of infection but don’t prove it — in two of those species and in four others, including red foxes and cats.

Another recently submitted paper also found signs of the pathogen infecting 17 percent of New York City sewer rats tested. And a small percentage of wild white-footed mice in Connecticut are also infected, according to research by Rebecca Earnest, a doctoral student at Yale University.

Questions about infection

But how are wild animals like deer being exposed to the virus?

The question is still unanswered, but there are theories. Wild animals can become infected by coming into close contact with human waste or sewage, or by inhaling the virus when close to humans. Exposure can also occur after interactions with domestic animals such as cats and dogs – or captive deer – which can carry the virus.

But “I think everyone agrees … that nobody knows,” Bushman says.

As many whitetails are being exposed, this is happening often. A 2021 study suggested that more than a third of deer in the northeastern and midwestern US were exposed. Another study found that the virus had entered deer at least four separate times from humans, and yet a third study found that the virus was passed back to a single human in Canada. (Read more: American wild deer found with coronavirus antibodies.)

One reason animal infections matter is because they represent new reservoirs for the virus, where it can harbor and acquire new mutations that could theoretically help it spread better if it finds its way back to humans.

“More transmission in more species is not something we want to see,” Earnest says.

Problem overlooked

The ability of SARS-CoV-2 to infect wildlife is a hidden panzootic—the animal version of an epidemic—with almost entirely unknown effects, Finkielstein says.

Infected animals often appear to have mild symptoms, but experts know almost nothing about how different variants of the virus affect most animals. Sometimes, the infections are fatal. The virus appears to kill a small percentage of infected mink, and three snow leopards died of complications from COVID-19 at the Lincoln Children’s Zoo in Nebraska.

Wilen cautions that we don’t really know how sick animals can be in the wild. He cites the example of chimpanzee immunodeficiency virus (SIVcpz), which jumped to humans and became HIV-1. SIV was long thought to cause only mild symptoms in chimpanzees, but research has finally determined that the virus can lead to an AIDS-like condition in animals that typically shortens their lifespan.

The effects of viruses are particularly difficult to study in wildlife, especially at the ecological level, Hoyt adds.

“We don’t know the consequences of this for wildlife,” agrees Finkielstein. “This is another aspect that has been largely ignored.”