For more than two years, COVID-19 has had its way with humanity. But humans are not the only victims of the virus. The disease, which leading theories still indicate spilled over from animals to humans in a Wuhan, China seafood wholesale market, has now infected pets and animals from farms, laboratories, and zoos. It has also found its way into the wild, infecting many non-domesticated species.
COVID-19 now appears to be widespread throughout the animal kingdom, according to a recent study in the journal Scientific Data that provides the first global case count of COVID-19 cases in animals. But there’s good news: other research has found that the highly infectious Omicron variant and its multiple subvariants might hit animals less hard than they hit us—transmitting less easily among them and causing less severe disease.
“To my knowledge, there is no obvious increase in reporting SARS-CoV-2 in animals after the emergence of BA.5,” says Amélie Desvars-Larrive, an assistant professor at the University of Veterinary Medicine Vienna in Austria and a co-author of the Scientific Data study. “Still, the kind of active monitoring and surveillance of animals that [has been] conducted is crucial. We should not think ‘human first,’ but rather integrate the knowledge about animals, humans, and their shared environment and develop a holistic approach for surveillance and control of SARS-CoV-2.”
In the study, researchers compiled reported incidents of COVID-19 by analyzing two animal health databases: the Program for Monitoring Emerging Diseases, a reporting system of the International Society for Infectious Diseases; and the World Animal Health Information System, to which veterinarians, wildlife conservationists, and other researchers report diagnoses of COVID-19 in non-humans. From February 2020 to June 2022, there have been 704 SARS-CoV-2 “animal events”—defined as a single case or multiple related cases within a given group, herd, or other population of animals—in 26 different species. The outbreaks have occurred in 39 countries across five continents, with Australia and Antarctica not reporting any cases. As for the total number of sick animals that represents? Just 2,058.
But that small number has big implications. Most of the reports indicate only the number of animals that tested positive, not the share they represent of a total number tested, so it is not possible to say what percentage of any animal population is harboring the virus.
“Obviously we see only the tip of the iceberg,” Desvars-Larrive says, because animals are tested for SARS-CoV-2 vastly less than humans are. “It’s impossible to answer how many animals are actually infected, but SARS-CoV-2 is a generalist coronavirus. Its capacity of adaptation to new hosts is impressive.”
Of all of the species studied, the American mink, with 787 cases reported, and the white-tailed deer, with 467, lead the pack. To be fair, that’s partly due to sample bias, Desvars-Larrive says. Mink have been extensively tested because they are bred on densely populated farms. (In November 2020, the government of Denmark ordered the killing of 12 million mink on farms when the virus began to spread through the species.) Deer, meanwhile, live near humans and are hunted for their meat, making sampling them for COVID-19 something that is in our own interest. Next on the list are domestic cats, at 338 cases, and domestic dogs, at 208. Further down are lions (68), tigers (62), and western lowland gorillas (23). The list tails off with assorted other animals including the black-tailed marmoset, Canada lynx, ring-tailed coati, and giant anteater, with one case each.
Other species of animals that didn’t make the list either have not been tested or may have a natural immunity—or at least resistance—to SARS-CoV-2. “Some animal species are more susceptible to coronaviruses,” Desvars-Larrive says. “This may be related to molecular mechanisms for virus entry or to some genetic mutations in the host.”
One question raised—but not answered—by the study is how animals are affected by Omicron and its subvariants, including BA.5, which are so highly transmissible among humans.
A handful of other studies to address that question have been conducted or are currently underway, however, and they show that animals are bearing up well against the new strains. Prior to the emergence of the Omicron variant and its numerous subvariants, researchers at Texas A&M University studied infection rates among dogs and cats living in homes in which at least one person had tested positive for COVID-19. Out of a sample group of 600 animals, they found 100 infections—or 16% of the total tested—presumably transmitted from the human to the pet. Some of the positive cases were symptomatic, with the animal coughing, sneezing, vomiting, or acting lethargic; others were asymptomatic.
A second phase of the study is now underway, since the emergence of Omicron and BA.5, and while only 100 animals have been tested so far, the difference in results is striking. “With Omicron and its subvariants being the dominant strains in humans, we’ve had only two positive animal infections so far,” says veterinary epidemiologist Sarah Hamer, director of the study. “So it’s definitely a lower infection prevalence now.”
Hamer stresses that the results are preliminary and the researchers have many more animals to test before the second phase of the research is completed—and she does not have a definitive answer as to why animal infection rates might be lower in the era of Omicron and BA.5. “Could it be that there’s something about this virus that’s just not infecting animals as much?: she asks. “Could it be that SARS-CoV-2 has been around for a while, and these animals have developed an immune response? We don’t yet know, but hopefully the test for neutralizing antibodies that we are doing now will help fill in these gaps.”
Similarly, other studies are showing that Omicron tends to cause less severe symptoms among animals than past variants, and researchers have ventured some theories as to why. In one study published in Nature in January 2022, investigators found that the Omicron variant was less pathogenic in laboratory mice and hamsters than earlier strains of SARS-CoV-2, and infected animals lost less weight and harbored less virus in their upper and lower respiratory tracts. The researchers did not determine exactly what makes Omicron less virulent among rodents, but offered some theories: with more than 30 mutations distinguishing the new variant from the original, the virus’s spike protein may engage less effectively with cell receptors in the animals. It’s also possible that changes in other proteins could slow viral replication in rodents, or even that the variant doesn’t multiply as effectively at a rodent’s body temperature as it does at human temperature. A study published in Nature in May yielded similar results with the BA.2 variant. This time, the researchers also noticed a reduced inflammatory response in the lungs of the animals.
Yet another study, published in April as a pre-print in bioRxiv, conducted analyses of 28 cats, 50 dogs and one rabbit living in households with humans infected with Omicron and found that just over 10% of the animals were positive for the virus, and none showed any clinical symptoms. Lidia Sánchez-Morales, a veterinary scientist at the University of Madrid and the lead author of the study, hypothesized about what could be protecting the animals.
“Numerous studies have shown that animals are less sensitive than humans to SARS-CoV-2 infection, which may be due to a lower affinity between the cell receptor and the binding viral receptor,” she wrote in an email. Specifically, she says, the ACE2 receptor in human cells to which the virus attaches is found to a lesser extent in animals, and Omicron may be less effective at overcoming this hurdle than the original virus. “This is why we conclude that the susceptibility of the companion animals to this variant seems to be much lower than in the other variants of concern known so far.”
But danger remains. The seemingly infinite mutability of SARS-CoV-2 means that new variants are certain to emerge. Desvars-Larrive worries that animals may serve as a sort of lab for the virus to try out new variants, before those novel strains jump to humans.
“The introduction and further spread of SARS-CoV-2 in an animal population might result in establishing an animal reservoir that can further maintain, disseminate, and drive the emergence of novel variants,” she says. “This is of particular concern for species that are abundant, live in social groups, and have close interactions with humans.”
This fact, Desvars-Larrive argues, calls for much more aggressive testing of wild, captive, and domestic animals. “Active monitoring and surveillance of animals is crucial,” she says. “This is the only way to get more data and to better understand the epidemiology of SARS-CoV-2, not only in animals but also at the human-animal interface.”
It’s at that interface that our own self-interest comes into play. What the animals catch, we often do, too. Looking out for them is one of the key steps to looking out for ourselves.
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Contributor: Jeffrey Kluger