Coronavirus in Animals: Implications for Veterinary Staff

Key Points

  • Ferrets are susceptible to infection by the SARS coronavirus (SARS-COv-1), but pathogenicity and host susceptibility can differ based on the viral infective dose and laboratory SARS coronavirus strain.
  • Studies are ongoing to investigate the respiratory pathology and transmission of COVID-19 (SARS-CoV-2) in experimental ferrets.
  • Conflicting reports, seen only as non-peer reviewed preprints, show ferrets can be infected with very large amounts of virus (multiple log 10 times than seen in natural human infections) and with laboratory attenuated strains of COVID-19 that may not occur in nature.
  • Pet owners should consult a veterinarian when a ferret develops a respiratory illness.
  • For pet owners with confirmed COVID-19 infection, the US Centers for Disease Control and Prevention advises another household member be designated to care for animals in the home and this individual should follow standard handwashing practices before and after interacting with pets.
  • If a person with COVID-19 must care for pets, they should wash their hands before and after caring for pets.
  • This content will be updated as new information becomes available from the studies that are ongoing.

What are coronaviruses?

Coronaviruses are a large group of viruses named for the crown-like spike proteins on their surface (Fig 1). These viruses belong to the enveloped RNA virus family Coronaviridae. Coronaviruses consist of single-stranded, positive-sense genomes, and are classified into four genera based on differences in their protein sequences:  alphacoronavirus, betacoronavirus, gammacoronavirus, or deltacoronavirus.1

Coronavirus diagram

Figure 1. Coronavirus diagram. Photo credit: Danvasilis via Wikimedia Commons (Click to enlarge)

Coronaviruses include many pathogens of mammals and birds that individually cause a remarkable variety of diseases, including pneumonia, reproductive disease, enteritis, polyserositis, sialodacryoadenitis, hepatitis, encephalomyelitis, nephritis, and various other disorders. Coronavirus and coronavirus-like infections have been described in swine, cattle, horses, camels, cats, dogs, rodents, birds, bats, rabbits, ferrets, mink, and various wildlife species, although many coronavirus infections are subclinical. In humans, coronaviruses are included in the spectrum of viruses that cause the common cold and more severe respiratory disease — specifically Severe Acute Respiratory Syndrome (SARS), caused by SARS-CoV-1, and Middle East respiratory syndrome (MERS), which are both zoonoses.

Severe Acute Respiratory Syndrome (SARS-CoV) likely originated in exotic animals from a Guangdong marketplace 2, specifically Himalayan palm civets (Paguma larvata) and raccoon dogs (Nyctereutes procyonoides).3,4 The disease then emerged to infect people and was first reported in Asia in 2002. Symptoms included fever, chills, and body aches, which sometimes progressed to pneumonia and acute respiratory distress, with a mortality rate of about 10%. SARS shocked the world by its high virulence and efficient transmissibility among humans 5, causing the first large-scale pandemic of the 21st century. The illness spread to over two dozen countries in North America, South America, Europe, and Asia; however, no human SARS cases have been reported anywhere in the world since 2004.2

Middle East Respiratory Syndrome or MERS-CoV originated in camels and emerged to infect people. This syndrome was first reported in 2012 in Saudi Arabia and spread to over 25 additional countries. Symptoms usually include fever, cough, and shortness of breath, which often progress to pneumonia. Approximately 30-40% of patients reported with MERS have died. MERS cases continue to occur, primarily in the Arabian Peninsula; however, as of 2019, there have been only two confirmed cases of MERS in the US, both in 2014.6

In 2019, a novel coronavirus (COVID-19 or SARS-CoV-2) emerged in Wuhan, China. Since then, cases have been detected in most countries worldwide and on March 11, 2020, the World Health Organization characterized the outbreak as a pandemic.7 The COVID-19 outbreak appears to have originated from a Wuhan seafood market where wild animals, including marmots, birds, rabbits, bats and snakes, are traded illegally. The first people infected with the disease, a group primarily made up of seafood market stallholders, contracted infection through animal contact.8

It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. If genetic manipulation had been performed, one of the several reverse-genetic systems available for coronaviruses would probably have been used. However, the genetic data irrefutably show that COVID-19 is not derived from any previously used virus backbone. Instead, two scenarios that can plausibly explain the origin of COVID-19: (1) natural selection in an animal host before zoonotic transfer, and (2) natural selection in humans following zoonotic transfer.9,10

What determines the host range of coronavirus?

The host range is defined as the range of species susceptible to a virus. One of the critical determinants of coronavirus host range is the interaction between the coronavirus spike protein and the host cell receptor. Angiotensin-converting enzyme 2 (ACE2) has been identified as a receptor for the attachment and uptake of SARS-CoV-1 and COVID-19 in host cells.11,12 The distribution of ACE2 in human tissues corresponds mainly to the cell types in which SARS-CoV replication has been observed. Besides type II pneumocytes and bronchial epithelial cells, ACE2 expression has been found in type I pneumocytes, endothelial cells, and smooth muscle cells of blood vessels, but not alveolar macrophages.13

Looking for additional information on coronaviruses and the structure of COVID-19? See “Determinants of Viral Infection: An Addendum to Coronaviruses in Animals” shared by Dr. Giacomo Rossi.

 

What is known about coronaviruses in ferrets?

My colleagues (SO, GR, KJD) and I are deeply concerned by reports of animal shelters being overwhelmed with abandoned and surrendered ferrets (Mustela putorius furo). We believe this is due to misdirected fear of infection by their owners, and we are concerned that a similar situation may arise in cats with reporting of non-peer-reviewed preprints about cats and COVID-19*. People in the Middle Ages killed many cats because they feared they were associated with transmission of the Black Death (Yersinia pestis plague). So let’s examine what we know about ferrets and COVID-19.

The reason that ferrets were among the first animals to be considered as COVID-19 hosts is because ferrets are the animal model for studying influenza and developing annual flu vaccines. Many laboratories around the world have colonies of ferrets for experimental research. These virus laboratories have skills in infecting animal models (including mice, hamsters, and monkeys), investigating clinical and pathological changes in infected animals, and measuring transmission of virus after experimental infection (duration of transmission and quantity of virus transmitted). Two reviews in the journal Veterinary Pathology describe SARS and MERS infection in animal models, including ferrets.14,15

Ferrets are susceptible to SARS-CoV-1 infection16 and can also transmit the virus at low levels by direct contact.12,15,17 In different studies, ferrets have shown diverse clinical signs, but in general the pathology seen was milder than that seen in humans and without significant mortality.16,18 Ferrets can develop a fever in response to infection, which is characteristic of SARS-CoV-1-infected human patients.19 However, there are conflicting reports regarding the histopathological lesions and severity of clinical signs in the ferret model that require further investigation.

For MERS-CoV, the host cell receptor is dipeptidyl peptidase IV (DPPIV) 20 , a ubiquitously expressed cell surface protein that functions in immune homeostasis. Interestingly, whereas MERS-CoV can utilize bat DPP4 (bDPP4), camel DPP4 (cDPP4), and human DPP4 (hDPP4) molecules for entry, it cannot infect cells using the DPP4 molecules from traditional small mammal models, including mice, ferrets, guinea pigs, and hamsters. The inability of MERS-CoV to infect these species in vivo and in vitro is primarily due to spike-receptor incompatibilities and not due to other species-specific host cell factors. Therefore ferrets are not susceptible to experimental MERS-CoV infection because their homologous DPP4 molecules do not function as receptors for MERS-CoV entry.21 Even after administering a high dose of MERS-CoV, no viral replication can be detected.22

As pathogenicity and host susceptibility may differ for different coronaviruses, it is currently unknown whether ferrets are susceptible to COVID-19 pathology and transmission. Wan et al 2020 23 looked at the spike protein of the COVID-19 virus, and the ACE2 receptor that SARS uses as its binding site to invade cells. Their analysis “confidently predicts” that the COVID-19 virus also uses ACE2 as its receptor. The authors predict that a single genetic mutation at one location in the virus’ genome could significantly enhance its ability to bind, and that surveillance for this mutation should be performed. The study also predicts that the COVID-19 virus can bind to ACE2 in ferrets (and pigs, cats and some non-human primates) with similar efficiency as it does in people.

Conflicting reports, seen only as non-peer reviewed preprints, show ferrets can be infected with very large amounts of virus (multiple log 10 times than seen in natural human infections) and with laboratory attenuated strains of COVID-19 that may not occur in nature. Some laboratory-infected ferrets show a fever, mild histopathological lesions, and low virus transmission. It is important not to make generalizations about the susceptibility of pet ferrets to natural COVID-19 infection, as research on the potential use of ferrets as an animal model for COVID-19 is being performed around the world, and all the findings are not yet submitted for publication.

Looking for additional information on coronavirus in ferrets or the role of other species in the receptivity of COVID-19? See “Determinants of Viral Infection: An Addendum to Coronaviruses in Animals” shared by Dr. Giacomo Rossi.

Also read the article authored by Dr. Donnelly for the Association of Exotic Mammal Veterinarians, made  available on April 9, 2020:  “From SARS to MERS, Thrusting Coronavirus into the Spotlight“.

Also see “COVID-19 And Pet Birds” by Dr. Stephanie Lamb on our sister site, Lafeber Pet Birds.

 

*Footnote: The preprint article by Zhang et al “SARS-CoV-2 neutralizing serum antibodies in cats: a serological investigation” submitted on April 3, 2020, states “A cohort of serum samples were collected from cats in Wuhan, including 102 sampled after COVID-19 outbreak, and 39 prior to the outbreak. 15 of 102 (14.7%) cat sera collected after the outbreak were positive for the receptor-binding domain (RBD) of SARS-CoV-2 by indirect enzyme-linked immunosorbent assay (ELISA)” has significant problems. First, while 15% of cats were found positive in Wuhan, only 0.5% of the human population (55,000 people) were found positive (Wuhan has a population of 11 million). Second, the results are based on an indirect ELISA. But there is not yet a validated human serological assay available for SARS-CoV-2, let alone an assay for cats. The commercially available human serology tests are not yet specific or sensitive enough to be used by public health authorities in the West because they are giving either high percentages of false positives or false negatives. Until further validation is conducted and published for domesticated animals, the cat serology results are meaningless.

 

Public health concerns

COVID-19 is primarily transmitted by direct person-to-person contact. There is no evidence of pets, domestic species, or wildlife in the United States playing any role in disease transmission. Coronaviruses are constantly mutating – they accumulate point mutations because of polymerase errors (infidelity) during transcription (genetic drift), and genetic recombination occurs at high frequency between the genomes of different but related coronaviruses during co-infection situations. This is why caution must be used when interpreting experimental animal infection with COVID-19, as multiple laboratory strains of COVID-19 exist due to natural coronavirus mutation through multiple cell cultures and/or collection from fluids and tissues of experimentally infected animals. Out of an abundance of caution, the U.S. Centers for Disease Control and Prevention recommends individuals positive for COVID-19 limit contact with pets and other animals.24

“Specifically, while a person infected with COVID-19 is symptomatic, they should maintain separation from household animals as they would with other household members, and avoid direct contact with pets, including petting, snuggling, being kissed or licked, sleeping in the same location, and sharing food…If possible, another household member should be designated to care for pets in the home and should follow standard handwashing practices before and after interacting with the household animal. If a person with COVID-19 must care for pets, they should ensure they wash their hands before and after caring for pets.”—Centers for Disease Control, Interim Guidance for Public Health Professionals Managing People with COVID-19 in Home Care and Isolation Who Have Pets or Other Animals 24

Any investigation into the contacts and exposures of infected or quarantined people should also include animals.

 

What should you do?

Pet owners should consult their veterinarian if a ferret develops respiratory illness . Telemedicine may be appropriate to provide veterinary consultation if the owner is positive for COVID-19.24 The US Food and Drug Administration recently announced that it intends to “temporarily suspend enforcement of portions of the federal veterinarian-client-patient relationship requirements” in order to allow veterinarians to better utilize telemedicine to address animal health needs during the pandemic.25 In turn, veterinarians should contact their State Veterinarian and Public Health Director if they encounter a companion animal with “a new, concerning illness” that lives in the same home as a person with COVID-19.24 Proper hygiene must be maintained during all human-animal contact.

Also refer pet owners to “If You Have Animals” by the US Centers for Disease Control and Prevention.

 

 

Stay informed

COVID-19 is an emerging infectious disease and our understanding is rapidly evolving. Get the latest public health information from:

 

 

Acknowledgments

Thank you to Drs. Yvonne van Zeeland and J.M.A. van den Brand for helpful input.

 

References