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Disclosures: Stone, Strosberg and Teres report no relevant financial disclosures.
December 21, 2021
7 min read
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Should we worry about animals with COVID-19?

Disclosures: Stone, Strosberg and Teres report no relevant financial disclosures.
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After devastating surges in hospitalizations and deaths, many look forward with some relief to the possibility of COVID-19 shifting into an endemic phase, like seasonal influenza.

Of course, this assumes that we keep up with vaccines, antivirals and traditional public health measures; but our relief may not be fully justified. Coronaviruses are found extensively in animal reservoirs to a much greater degree than influenza. Should we worry about SARS-CoV-2 infections in domestic and wild animals? And what about the more highly transmissible delta variant or the emergence of new variants?

Source: Adobe Stock.
Hippos recently tested positive for COVID-19 in Belgium. Source: Adobe Stock.

Animals and coronaviruses

Pathogenic coronaviruses (CV) infect many species of birds and mammals, including humans. And some coronaviruses cause significant morbidity and mortality in neonatal animals such as kittens, calves and piglets. At birth, however, these neonates are often protected from clinical disease due to ingestion of colostrum, which contains protective antibodies.

CV and CV-like infections (although many are subclinical) have commonly been described in swine, cattle, horses, camels, cats, dogs, rodents, birds, bats, rabbits, ferrets, mink and various wildlife species (Machlachlan and colleagues). In swine and some ruminants, CV is ubiquitous. These viruses are more commonly associated with the gastrointestinal tract than in the respiratory tract. Nonetheless, CV is part of the serious swine respiratory disease complex associated with five viruses. CVs also contribute to significant morbidity (weight loss) in dairy and beef cattle.

Feline infectious peritonitis is caused by a CV. Kittens commonly carry an avirulent enteric strain, replicating in enterocytes. But, when a genetic mutation occurs, a systemic infection follows with severe immune-mediated pathology and high mortality, according to Hartmann and colleagues. Ninety percent of cats in catteries carry specific CV antibodies. Pig cells express the same ACE2 receptors as human cells and are susceptible to CV. Edwards and colleagues reported that in China in 2018, pigs became infected with a deadly CV diarrheal disease that impacted piglets, 5 days of age. The virus was transmitted by a horseshoe bat and killed 25,000 piglets, according to the NIH. The Veterinary Diagnostic Laboratory at the University of Minnesota reported that another CV, the swine enteric coronavirus disease, caused the death of more than 8 million pigs in the United States and Canada in 2013. And chickens, turkeys and pheasants are prone to a CV that causes infectious bronchitis, according to a 2007 report in Avian Pathology.

Animals are getting COVID-19

Zoo animals are in the news. A tiger in a Swedish zoo developed respiratory symptoms and rapidly deteriorated with acute respiratory distress and was euthanized. Forbes reported that the causative agent was COVID-19 with variant B1.177,21, the alpha U.K. strain. At the San Diego Zoo, cats and primates have been vaccinated. However, three Malayan tigers got breakthrough respiratory infections, according to the San Diego Union-Tribune. Their treatment included quarantining in addition to the administration of nonhuman monoclonal antibodies and antibiotics in case of a bacterial component. The tigers recovered. The New York Times reported that at a Nebraska zoo, three snow leopards recently died from complications of COVID-19.

Most recently, CNN reported that two hippos tested positive for COVID-19 in a Belgian zoo, believed to be the first such infection reported in the species. They both had mild symptoms, according to the zoo.

Red flag: COVID-19 outbreak in mink — zoonotic spread

In 2020, COVID-19 broke out on two mink farms in the Netherlands, rapidly spreading to 70 farms, leading to deaths and the culling of 20 million mink, according to a report in Science. Mink, susceptible to COVID-19 and living in packed cages, developed respiratory symptoms. The virus mutated, infecting workers with the variant found in the mink. This jump back to humans is the definition of zoonotic spread (Munnink and colleagues). COVID-19 has been confirmed at mink farms in Utah and Wisconsin, but thus far there has been no zoonotic spread to humans.

Red flag: White-tailed deer — true animal reservoir?

An important distinction should be made between a temporary animal host and an animal reservoir. For example, a pet cat can get COVID-19 from its owner. After a short respiratory illness, it makes a full recovery but spreads it to no other pet cats or humans. In contrast, deer may become a potential COVID-19 reservoir as deer-to-deer transmission and ensuing infections in some deer populations appears to have been established. In a recent study published on the preprint server bioRxiv, 30% of Iowa white-tailed deer tested positive for COVID-19 found in retropharyngeal lymph nodes. It is not known how the virus spreads from humans to deer and, thus far, no humans have been infected by deer. Yet, the deer are not dying, and the virus is clearly spreading. This discovery that deer can survive with infection and transmit the virus to other deer sets the stage for deer populations to potentially maintain the virus over time and become a well-defined, true animal reservoir for COVID-19. (Bats were likely the first true reservoir.) Predators kill and eat fresh meat composed of infected lymph glands and upper respiratory tissue, thus promoting potential spread both up and down the food chain, including vultures who clean up the carcass. What are the implications for hunters and for those butchering the animal?

COVID-19 in wild animals can mutate. And there is a big difference between infection in domesticated production animals that die or get culled in contrast to infection in wild animals. There are considerable disease control opportunities when dealing with production animals. For example, when food animals are sent to commercial slaughter, both antemortem and postmortem inspections are done with facilities being deep-cleaned between shifts. In swine production, often an “all in, all out” system is used for feeder pigs in which the facilities are cleaned and left vacant for a time after each group. No such controls exist in wild animals. What if the delta variant gets into wild animals, or if further mutations occur with the emergence of even more virulent variants for humans? Due to the high efficiency of human-to-human transmission of COVID-19, it takes only one animal-to-human transmission to make a difference.

Perhaps the risk to humans from animals is low

In a balanced and reasoned analysis of the potential COVID-19 risk to humans from animal populations, Smriti Mallapaty reviewed the extensive animal surveys carried out by the World Organization for Animal Health, WHO, the U.S. Department of Agriculture and the CDC. The evidence indicates that pigs, the most susceptible, with ACE2, have poor replication of the SARS-CoV-2 virus on challenge testing. Only two species of bats — the horseshoe bat and a fruit bat — carry CV. Animals in closer proximity to people, including voles, racoons, cows, ducks and chickens, seem mostly resistant to COVID-19. Animals more likely to harbor the SARS-CoV-2 virus, including ferrets, cats, raccoons and racoon dogs, don’t get sick or get mild disease upon exposure. The one notable exception from this list was the example of the Dutch mink farms and the documented zoonotic transmission.

What’s next: Water buffalo and pangolin

What are the likely next animals to harbor SARS-CoV-2? Ilya R. Fischhoff, PhD, from Barbara Han’s lab at the Cary Institute of Ecosystem Studies in New York, used a machine-learning tool to predict binding between the ACE2 protein in mammals to the spike protein from the original wild type SARS-CoV-2 (not with any of the variants). The researchers used artificial intelligence modeling on transmissibility and other ecological traits. They then tested the model with surveillance and lab tests. High on the list were mink, bats, rodents, water buffalo and pangolin.

Conclusions: The animal-human interface

The likelihood of zoonotic transmission from animal to human of a mutant SARS-CoV-2 strain is unclear. What is clear is that we need to encourage and support surveillance and monitoring of both domestic and wild animals, which includes genetic sequencing. Furthermore, we need to ensure that there is adequate funding for responsible national and international organizations. We would do well to adopt a One Health approach, which advocates for increased collaboration between the veterinary world and the human medical world in the face of accelerating urbanization, climate change, ecological degradation and increasing interaction between humans and animals. The best way to prevent animal infections is to vaccinate the main reservoir — humans. In the meantime, let’s hold our breath!

References:

Cavanagh D. Avian Pathol. 2007;doi:10.1080/03079450500367682.

Edwards CE, et al. Proc Natl Acad Sci U S A. 2020;doi:10.1073/pnas.2001046117.

Enserink M. Science. 2020;doi:10.1126/science.368.6496.1169.

Fischhoff IR, et al. Proc Biol Sci. 2021;doi:10.1098/rspb.2021.1651.

Hartman K. Vet Clin N America. 2005;doi:10.1016/j.cvsm.2004.10.011.

Kuchipudi SV, et al. bioRxiv. 2021;doi:10.1126/science.abe5901.

Machlachlan et al. Fenner’s Veterinary Virology, 5th Edition, Elsevier, 2017.

Mackenzie JS, Jeggo M. Trop Med Infect Dis. 2019;doi:10.3390/tropicalmed4020088.

Mallapaty S. Nature. 2021;doi: 10.1038/d41586-021-00531-z.

Mawad D, Hu C. Runny-nosed hippos test positive for Covid-19 in Belgium. CNN. Published Dec. 5, 2021. https://www.cnn.com/2021/12/05/americas/covid-19-hippos-belgium-intl/index.html. Accessed Dec. 8, 2021.

NIH. New coronavirus emerges from bats in China, devastates young swine. https://www.nih.gov/news-events/news-releases/new-coronavirus-emerges-bats-china-devastates-young-swine. Accessed Dec. 8, 2021.

Oude Munnink BB, et al. Science. 2021;doi:10.1126/science.abe5901.

Poultry World. Birds culled as UK forced to close plants due to Covid-19. Published Aug. 31, 2021. https://www.poultryworld.net/Health/Articles/2020/8/Birds-culled-as-UK-forced-to-close-plants-due-to-Covid-19-634009E/. Accessed Dec. 17, 2024.

Ramos VM. Three ‘beloved’ snow leopards died of Covid complications at Nebraska zoo. The New York Times. Published Nov. 13, 2021. https://www.nytimes.com/2021/11/13/us/snow-leopards-covid-nebraska-zoo.html. Accessed Dec. 8, 2021.

Stone J. Covid killed a tiger. Are your house cats at risk? Forbes. Published Jan. 26, 2021. https://www.forbes.com/sites/judystone/2021/01/26/covid-killed-a-tiger-are-your-house-cats-at-risk/?sh=43a8dc0b2cb2. Accessed Dec. 8, 2021.

Wosen J. 3 vaccinated tigers have COVID-19 at the San Diego Zoo. San Diego Union-Tribune. Published Oct. 27, 2021. https://www.sandiegouniontribune.com/local/story/2021-10-27/breakthrough-covid-infections-happen-in-vaccinated-animals-too-san-diego-zoo-learns. Accessed Dec. 8, 2021.