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March 15, 2021

Racing to save humans through animal research

Veterinary researchers strengthen understanding of, responses to SARS-CoV-2

Illustration by Valentina Talijan

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Dr. Jurgen A. Richt’s team began studies on SARS-CoV-2 infection in animals months before funding arrived.

Dr. Richt, a professor at Kansas State University College of Veterinary Medicine and member of a World Health Organization panel on COVID-19 animal model development, almost emptied his $200,000 war chest of donations and other savings before the university and federal agencies began funding his research. In the meantime, his team of about 20 scientists began experiments early in the pandemic to determine which animals can become infected with SARS-CoV-2, the virus that causes COVID-19 in humans, and which animals could be models for human infection.

Masked veterinary researcher looking through a microscope

His studies since include which animals could become viral reservoirs or spread SARS-CoV-2 to wildlife, how the virus changes inside cats, how cats spread the virus indoors, and how long the virus remains viable with various weather and surface combinations. His team found pigs were unlikely to be important carriers of SARS-CoV-2 and unsuitable as preclinical animal models.

Dr. Richt’s team described the study on SARS-CoV-2 transmission among cats in an article published in Emerging Microbes and Infections.

“What concerns me about the cat study is, obviously, if we have efficient transmission from humans to cats and from cats to cats, there will be also, most likely, the possibility cats can infect humans and other animals,” Dr. Richt said.

Veterinary scientist work in SARS-CoV-2 research is ubiquitous, essential, and hard to quantify. These scientists describe their fears SARS-CoV-2 could multiply and mutate in animals, their admiration for the genius of their colleagues and collaborators, the pull to work on multiple urgent studies on public health and animal health aspects of the pandemic, and the expertise veterinarians bring to controlling disease spread in any animal population.

Dr. Andrew T. Maccabe, CEO of the Association of American Veterinary Medical Colleges, said nearly all AAVMC member institutions are part of universitywide SARS-CoV-2 research enterprises, often in collaborations with medical schools. The work includes efforts to improve understanding of transmission within and across species, public health, and diagnostic testing.

“Veterinary medicine is an integral part of any comprehensive response plan to a pandemic,” he said. “This virus happens to have an animal reservoir, which makes the link even easier to see. But even if it didn’t, there are fundamental approaches to preparedness and response that are directly relevant to veterinary medicine.”

Dr. Casey Barton Behravesh, director of the Centers for Disease Control and Prevention One Health Office and captain in the U.S. Public Health Service, said in a message that veterinarians play a crucial role in studying SARS-CoV-2 in animals at the CDC and other federal and local agencies.

“Without the research and expertise of CDC veterinarians, our current understanding of SARS-CoV-2 in animals in the U.S. and globally would be limited,” she said. “CDC’s veterinary experts have helped us to test and gather data about people and animals—both domestic and wildlife—and SARS-CoV-2; provide much-needed assistance to local and state jurisdictions investigating people and animals with SARS-CoV-2 in settings including households, mink farms, zoos, animal shelters, and other settings; and add to our understanding of how this emerging infectious disease might affect animals and the role different types of animals could play in the spread of SARS-CoV-2 to people.”

Veterinary staff members swab the mouth of a pet ferret
Veterinary staff members at the Cummings Veterinary Medical Center at Tufts University swab the mouth of a pet ferret for SARS-CoV-2 epidemiological research. (Courtesy of Tufts)

A spokesperson for Pfizer said several veterinarians worked on safety studies for the company’s human-use COVID-19 vaccine, specifically in its comparative medicine group. At press time, officials from Moderna had not confirmed veterinarians were on the teams that developed its COVID-19 vaccine.

Risk potential in animals

Tufts University virologist and disease ecologist Dr. Jonathan A. Runstadler leads a team in the Cummings School of Veterinary Medicine that began collecting SARS-CoV-2 samples in February 2020, at first working to determine whether the staff at the teaching hospital risked exposure through pets. His long-term goal is to understand how the virus could spill back and forth between species.

As of early February, his team had collected about 3,200 samples from 1,700 animals, a combined total of nasal, oral, and anal swabs as well as serum samples. About 2,000 of those samples came from dogs or cats, and the rest came from another 63 species of nearby bats and other wildlife in New England and zoo animals.

“It’s a good thing that we haven’t really seen spillover in ways that we thought might be possible, particularly as the pandemic spread among the human population” and the virus became more widespread, he said.

But COVID-19 remains an emerging disease, and Dr. Runstadler sees a responsibility as part of a veterinary school and the veterinary profession to maintain surveillance in animals and to work to end the pandemic.

“We’ve got veterinarians here and elsewhere who are doing really critical work on animal models and animal model development and working on vaccine development,” he said.

USDA Animal and Plant Health Inspection Service officials catalogue reports on animals with confirmed positive tests for SARS-CoV-2 infection. As of Jan. 15, animals had been infected in at least 131 incidents, 58 of them involving domestic cats and 41 involving dogs. Although only 16 incidents involved mink, those outbreaks sickened and killed unknown numbers of animals on farms in Michigan, Oregon, Utah, and Wisconsin.

So far, mink have been the only farmed animals known to be susceptible to SARS-CoV-2 infection, and a mink captured and tested near a farm in Utah remains the only wild animal positive for the virus, APHIS officials said.

Emma Moran, PhD, a biological science specialist who has led a COVID-19 rapid response program for the USDA National Institute of Food and Agriculture, said the agency issued two $1 million grants to fund research projects at veterinary colleges to examine potential SARS-CoV-2 replication and mutation in pig, chicken, and cattle cells and to examine beef cattle susceptibility and viral contamination in food processing. Another $350,000 grant is funding studies on potential susceptibility and transmission in deer and elk.

Mark Mirando, PhD, who is a biological science specialist for NIFA, national science liaison for animal production systems, and science coordinator for the NIFA Agriculture and Food Research Initiative, said NIFA has other grants available in case SARS-CoV-2 variants become greater threats to livestock. And he noted that NIFA and APHIS fund the National Animal Health Laboratory Network that is supporting research into potential infections across animal species.

Making the next vaccine

The work in veterinary colleges extends to developing the next generation of human-use COVID-19 vaccines.

Mary Jackson, PhD, a bacteriology professor in the Mycobacteria Research Laboratories and Department of Microbiology, Immunology, and Pathology at Colorado State University College of Veterinary Medicine & Biomedical Sciences sees potential to adapt an existing vaccine against tuberculosis as a vaccine against SARS-CoV-2.

The recombinant COVID-19 vaccine would be based on the century-old bacillus Calmette-Guerin tuberculosis vaccine. The BCG vaccine has been known for decades to improve immunity against viral pathogens and reduce illnesses and deaths among children and the elderly, and recent epidemiologic studies suggest potential to reduce the prevalence and severity of COVID-19 symptoms, according to project information filed with the National Institutes of Health, which is providing $412,000 toward the project.

Dr. Jackson said she sees potential to use the vaccine as a platform for a new vaccine that expresses specific antigens of SARS-CoV-2.

“We are testing multiple constructions, and I would say we have more than 12 right now that we are exploring,” Dr. Jackson said.

Veterinary researchers at the University of Wisconsin-Madison and The Ohio State University are developing vaccine candidates adapted from influenza and measles vaccines, respectively, according to university announcements. Others at Colorado State are collaborating on studies to use ultraviolet light and riboflavin to create an inactivated virus for a COVID-19 vaccine candidate, and Purdue University veterinary scientists are developing an adenovirus-based vaccine platform.

Company officials for Applied DNA Sciences announced in November plans to conduct clinical trials on feline-use vaccine candidates against SARS-CoV-2 infection, in collaboration with EvviVax and Guardian Veterinary Specialists.

Robert Weiss, PhD, said researchers at the Cornell University College of Veterinary Medicine have pursued studies in not only vaccine development for human medicine but also diagnostics, assays of host antibodies in serum and saliva samples, therapeutics to impair viral transmission and replication, and fundamental understanding of the mechanisms used by SARS-CoV-2, in addition to the work by the state veterinary diagnostic laboratory housed in the veterinary college to test about 5,000 COVID-19 samples from students daily.

Collaboration between the veterinary college and Cornell Engineering, for example, is helping disease experts image the SARS-CoV-2 virus, understand its structure, and potentially see weaknesses to exploit, he said.

Studying a virus, applying the One-Health concept

Dr. Rebecca Lee Smith, a veterinary epidemiologist and associate professor of epidemiology at the University of Illinois College of Veterinary Medicine, started work in spring 2020 on a team that decided whom to test at the university, how often to test, what messages to send out, and how to coordinate quarantines. She studies incoming data from the 10,000 COVID-19 tests processed by the Veterinary Diagnostic Laboratory each weekday and 45,000 processed each weekend, and she talks with other health leaders on and off campus about what interventions are working and what’s needed.

She also leads work on a monthly survey that asks all the people on campus about their activities and perceptions of risk, with goals of identifying what makes people more likely to test positive for SARS-CoV-2 and developing messages to encourage better behavior.

“A lot of the work that I do, although it’s very much in the human realm, I’m bringing in things that are very common in veterinary epidemiology and are not well known in human epidemiology,” Dr. Smith said. “So, thinking about risk-based surveillance, which we do in livestock fairly frequently, that isn’t something you see in human epidemiology.”

Adjusting the frequency of COVID-19 testing based on risk calculations, for example, helped U of I control pockets of infection. One ongoing study examines how to minimize the frequency of testing in humans yet maximize sensitivity to infections, adapting techniques developed to minimize stress in zoo populations, Dr. Smith said.

“Veterinary epidemiologists in particular really should step up and help here because we have a lot of experience within the realm of infectious disease control—and with limited resources,” Dr. Smith said.

Dr. John Middleton, who is a professor of food animal medicine and surgery at the University of Missouri College of Veterinary Medicine and chair of the AVMA Council on Research, is working with colleagues in the university’s schools of medicine and health professions to study links among infections, perceptions, and mitigation efforts, among other projects.

“These emerging viral threats potentially come from animals, and so veterinarians have a role and veterinary colleges certainly have a role in helping us understand these diseases,” he said. “And I think you’ll find there are experts in veterinary schools who understand coronavirus and, therefore, that is certainly helpful in allowing us to understand this coronavirus.”

Isaac Pessah, PhD, associate dean and professor of molecular biosciences at the University of California-Davis School of Veterinary Medicine, described the pandemic as a hallmark moment for veterinarians working in the one-health area, especially for those working on viral infectious diseases. Past research into infectious immunologic disorders shows the benefits of interdisciplinary approaches, embracing the study of diseases in animals to understand their effects in humans, Dr. Pessah said.

The one-health concept, once nebulously defined, is gaining acceptance as diseases emerge, a problem that rises in frequency with additional human incursions at wildlife boundaries.

“(Such a) disease isn’t necessarily going to stay local, as we now know with COVID-19,” Dr. Pessah said. “It can go global very quickly. And although we think we’re ready and able to deal with it—wow, obviously not good enough, with all of our technology.”

Dr. Udeni B.R. Balasuriya, director of the Louisiana Animal Disease Diagnostic Laboratory and professor of virology at the Louisiana State University School of Veterinary Medicine, collaborates with Dr. Richt on studies to develop animal models to test antiviral drugs and vaccines and collaborates with U.S. Geological Survey scientists who are studying SARS-CoV-2 susceptibility in North American bats, among other studies he and colleagues have been conducting or aiding through the diagnostic laboratory. The pandemic showed veterinary laboratories’ capacity to process large numbers of samples for human medicine, he said.

“We have a major role in public health, but we are not that recognized,” he said.

Dr. Maccabe of the AAVMC said people will need to remember the importance of supporting veterinary research as the world emerges from the pandemic.

“There is a great deal of capacity at our veterinary medical colleges, and we need to preserve and protect that capacity,” he said.