During the first few years of the COVID-19 pandemic, the virus SARS-CoV-2 was detected in an increasing number of non-human animal species. This included many wild animal species as well as domestic animals such as dogs and cats.
In some animals, like the white-tailed deer and mink, scientists found that the virus spread readily within the species, and then, with newly acquired mutations, spilled back into the human population. This sparked concern that a parallel evolution of SARS-CoV-2 in animals could create a more transmissible or pathogenic variant that could reignite a surge in human infection.
So where do things stand today? In a new study, Yale researchers investigated just that. They conducted surveillance studies to understand the current coronaviral landscape of wild and domestic animals in the northeastern United States. They found that while SARS-CoV-2 continues evolving in humans, its grip on the animal kingdom seems to be weakening.
"This is good news as this reduces the chance of spillback of newly evolved animal variants into humans," said Caroline Zeiss, professor of comparative medicine and of ophthalmology and visual science at Yale School of Medicine (YSM) and senior author of the new study.
She added: "Ongoing monitoring is essential, particularly for viruses that are capable of infecting many species such as corona and influenza viruses. Long-term surveillance of wildlife and animals living close to humans gives us a unique chance to spot new pathogens that might spread to humans or affect animal health."
The study appears in the journal Scientific Reports.
Surveilling viruses
Coronaviruses can have a very broad host range and jump across animal species. This ability was at the root of the SARS CoV-2 virus crossing the animal-human boundary to trigger the COVID-19 pandemic, scientists say. Since its emergence, SARS-CoV-2 has undergone rapid evolution, with one variant succeeding another as the virus became increasingly transmissible in its predominant human host. This progression has been accompanied by evidence for human-to-animal transmission of circulating variants, as well as sustained transmission within certain species like the white-tailed deer. Rates of SARS-CoV-2 prevalence or infection in animal samples have declined since the peak of the pandemic. But it's been unclear whether that reflects an actual decline in rates or reduced resources for surveillance studies.
For the new study, the researchers wanted to get closer to understanding just that. So, they conducted a broad surveillance study of SARS-CoV-2 in wild and domestic animal species in the northeastern U.S., including cats, dogs, ferrets, woodchucks, cattle, and more. They collected fecal swabs, oral swabs, or stool specimens from 889 animals. Collection of these samples was a collaborative effort between the Connecticut Veterinary Medical Diagnostic Laboratory at the University of Connecticut, the Connecticut Agricultural Experiment Station, and Yale University.
Samples were analyzed for coronaviral RNA using an assay method that is able to detect a broad range of coronavirus types. Positive samples were then sequenced to identify the coronavirus species within the sample. In addition, researchers conducted a genetic analysis of most of the positive samples to provide independent verification of their results.
To complement the surveillance study, they conducted experimental infections of white-footed mice in the laboratory using the original strain of SARS-CoV-2 and the more recent Omicron variant. They focused on white-footed mice as they are the most common wild rodents in the area. They also have a known role in the spread of pathogens between humans and other animals like the white-tailed deer. And, to test cross-species transmission, they exposed hamsters - which are known to be a very good and susceptible model of SARS-CoV-2 infection - to contaminated bedding and cages from the mice infected with SARS-CoV-2.
"Our goal was to determine whether both variants could infect white-footed mice and whether they could transmit the virus to each another or to another species," Zeiss said.
Protecting our pets
Through both the surveillance and lab studies, the researchers detected several kinds of animal coronaviruses in samples from seven different species, though none of them had SARS-CoV-2. When they infected the white-footed mice with SARS-CoV-2, the mice could catch both the original and Omicron variants, though they didn't shed as much of the virus with the Omicron variant and did not transmit it between them. Importantly, the original strain could spread among the mice, but neither the original nor the Omicron version could jump to another species like hamsters.
Taken together, researchers say, the findings suggest that as SARS-CoV-2 continues evolving in its preferred host (humans), successive variants may be losing their affinity for non-human animals.
"Therefore, the chance of spillback of newly evolved animal variants into humans is very low," Zeiss said. "For most people, this is relevant to pet owners who live in close contact with animals."
Other Yale authors include Sylvester Ibemgbo, a postdoctoral associate at YSM; Susan Compton, a senior research scientist in comparative medicine at YSM; Nathan Grubaugh, an associate professor of epidemiology (microbial diseases) at the Yale School of Public Health (YSPH); Seth Redmond, an associate research scientist in epidemiology (microbial diseases) at YSPH; Mallery Breban, a program administrator at YSPH; Gregory Watkins-Colwell, a senior collections manager at the Yale Peabody Museum; and Kristof Zyskowski, a collections manager the Yale Peabody Museum. Authors at collaborating institutions include Guillermo Risatti and Margot Syracuse at the Connecticut Veterinary Medical Diagnostic Laboratory, and Megan Linkse and Scott Williams at the Connecticut Agricultural Experiment Station.
This study was supported by the United States Department of Agriculture.
