Why you should be concerned about Covid in animals

Barbara Han of the Cary Institute for Ecosystem Studies, an expert in disease ecology, knew it was a matter of when the coronavirus would infect animals, not whether or not it would.

In 2020, when the first news of infected animals arrived, she started working on an artificial intelligence model that could predict which animals would be hit next.

“Our very ambitious goal was to be able to predict exactly which species we should be looking at, given how we thought the virus was going to spread,” Han said.

As his team worked, the stream of coronavirus cases in new species became a flurry: domestic dogs and cats, breeding mink.

The virus has infiltrated zoos, infecting the most predictable animals (tigers and lions) as well as the most surprising species (the coati, native to the Americas and reminiscent of a raccoon-lemur cross, and the native binturong, or Asian cat-bear). from Southeast Asia and reminiscent of a cross between a raccoon and an elderly man).

Han and his colleagues ended up identifying 540 mammal species most likely to host and transmit the coronavirus. She was especially concerned that the red fox, one of the first on her list of animals at risk and which is found in large numbers in Europe and North America, would be susceptible to the virus.

We’re just waiting for someone to notify us of this,” she said.

In fact, just a few days earlier, researchers in Colorado had announced that the virus could infect red foxes in the laboratory.

“Oh no!” exclaimed Han when she was told. “When you do a job like mine, it’s really annoying to find out you got a prediction right.”

Last fall, scientists who analyzed biological tissue samples from whitewood deer in Iowa found that the virus was widely present in this species. The discovery has heightened fears that the virus could establish itself in an animal reservoir, mutate and spread to other species, including back to humans.

And that opened up a frightening prospect: if deer can silently spread the coronavirus, what other animals can do? And which ones will?

Experts say there’s no need to panic and stress that it’s not the animals to blame.

“It’s humans who are infecting the animals. Now the animals are sick, and some are dying,” Han said.

Identifying species at risk is crucial to protecting the health of both humans and animals. It is also a complex scientific problem, involving a wide range of potentially vulnerable species. Scientists need to analyze a constant, chaotic stream of computer-traced predictions, laboratory data, and confirmed infections in zoos, homes, and in the wild.

In an ideal world, scientists would monitor all potentially susceptible populations. But in the real world, they are trying to strike a delicate balance between identifying the species of greatest concern and broadening the scope of their research as the virus mutates and new variants emerge.

“It wouldn’t surprise me if we found an animal species or animal reservoir that no one thought of,” said virologist Diego Diel of Cornell University.

The basics of infection

Scientists use different tools to identify susceptible species. Each approach has its limitations, but taken together they paint a more complete picture of which animals are at risk.

Some teams of scientists are focusing on the ACE2 receptor, a protein found on the surface of cells in many species. The spiky protrusions of the coronavirus allow it to attach to these receptors, like a key going into a lock, and penetrate cells.

In 2020, a group of scientists compared the ACE2 receptors of hundreds of vertebrate animals, mostly mammals, with those of humans, to determine which species the virus could infect. (The ACE2 receptors of birds, reptiles, fish, and amphibians do not bear enough resemblance to our own to cause concern.)

“The predictions have been pretty good so far,” wrote biologist Harris A. Lewin of the University of California at Davis and one of the study’s authors in an e-mail. Scientists predicted, for example, that whitetail deer were at high risk of infection.

But some of the predictions were entirely wrong: The paper identified farmed mink as a species of “very small” concern — and then, in April 2020, the infection ran rampant in mink farms.

In fact, ACE2 only provides a snapshot of virus susceptibility.

“Viral infection and immunity against viruses is much more complex than simply a virus attaching to a cell,” virologist Kaitlin Sawatzki of Tufts University said in an email.

And of the nearly 6,000 species of mammals in the world, scientists have so far sequenced the ACE2 receptors of just a few hundred, creating a skewed dataset.

Thus, scientists need to look for creative ways to make predictions for animals whose ACE2 sequences are not yet known. ACE2 sequences play a crucial role in basic biological functions such as blood pressure regulation.

Gathering the basic details of a species’ life history — what it feeds on, whether it’s nocturnal or not, etc. — Han’s team trained a machine-learning algorithm to identify the ones that seemed most likely to stick. up to the virus and transmit it. This allowed them to predict the susceptibility to the virus of many other mammals.

Scientists can test computerized predictions in the lab, trying to infect cells from animals or live animals with the virus. Such experiments can differentiate species that may look similar. A study found that rodents of the Peromyscus species can be infected by the original version of the virus and can transmit it, which is not the case for mice (of the Mus species).

But something that happens in a collection of cells doesn’t always happen in real animals, and what happens in a laboratory, where animals are often given high doses of the virus, may not reflect real life. For example, although the original virus can replicate in swine cell lines, the researchers found that swine did not appear to be highly susceptible to it.

To find out if animals have been infected with the virus in the real world, scientists can perform so-called serological studies, looking for antibodies to the coronavirus in their blood.

“Serology helps us analyze historical exposure,” said Dr. Suresh Kuchipudi, a veterinary microbiologist at Penn State University.

Bats have been of concern because they are reservoirs for other coronaviruses, and many scientists think that Sars-CoV-2 initially emerged from bats. But bat species are incredibly diverse, and not all appear to be susceptible to the virus. According to the scientists, this highlights the fact that the animals that cause the most concern may not be the most obvious.

To complicate matters, the virus is not static, and animals that have resisted infection with past variants may be vulnerable to newer variants. For example, laboratory mice that were not susceptible to the original coronavirus or the delta variant were susceptible to the beta and gamma variants.

“That’s the problem with emerging diseases,” said Scott Weese, an infectious disease veterinarian at the University of Guelph, Ontario (CAN). “We have to continually update our knowledge every time something changes.”

A shortlist of species

Biological vulnerability is just one piece of the puzzle. Whether an animal species can become a reservoir of viruses depends on a constellation of factors.

“It depends on the social behavior of the species, the immune response of the animals, the size of the population, the types of links with different populations of animals,” said Keith Hamilton, director of the preparedness and resilience department at the World Organization for Animal Health.

In the case of a virus that is transmitted mainly by humans, the relationship of an animal species with us is of enormous importance. While the narwhal’s ACE2 receptors put them at “high risk of infection,” officially speaking, one of them is unlikely to bump into one of us.

Dogs, cats and pet hamsters can all be infected by the virus. It is likely that hamsters from a pet store in Hong Kong infected two people, a fact that led to a massive mass sacrifice of hamsters, which sparked controversy.

But we are far more likely to pass the virus to our pets than they are to infect us, and, scientists have predicted, many of these infections will not go ahead. Infectious pets can also be isolated.

“The hamster that you bought a long time ago and lives in your house is not a big risk to you,” Hamilton said.

For scientists, a major concern is the so-called “peridomestic” species that live alongside us but move freely. In North America, they include rodents of the genus Peromyscus, red foxes, and feral cats.

These animals can act as bridges between humans and wild populations, spreading the virus to species with which we possibly have no contact. And rodents, which are reservoirs for other pathogens, “should definitely be at the top of the list,” Kuchipudi said.

To monitor this potential risk, officials at the US Department of Agriculture and other agencies are looking for signs of the virus in some of these animals that live in zoos, reserves and mink farms. These include rodents, skunks, foxes and skunks.

Globally, certain endangered species are also of concern. Three snow leopards at a zoo in Nebraska have died after contracting the coronavirus, and a wild leopard cub in India has been discovered infected with the virus.

Great apes, which have frequent contact with tourists and scientists, are vulnerable to other respiratory viruses.

“Great apes are uniquely susceptible to human pathogens because there is a close genetic relationship between them and us,” said Kirsten Gilardi, a wildlife veterinarian at the University of California, Davis.

So far, no cases of wild primates infected with the coronavirus have been reported, but researchers are monitoring the animals closely, taking fecal samples from those with respiratory illnesses.

^{Translation by Clara Allain}