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dcyphr | Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2

Abstract


Since SARS-CoV-2 is thought to have originated from bats, it is of significant importance that we observe the susceptibility of other animals as a potential transmission route. In this study the researchers investigate how susceptible ferrets and other animals that are in close contact with humans are to SARS-CoV-2. The researchers found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks. However ferrets and cats are not as resistant to infection as the other animals studied. Specifically, cats appear to be susceptible to airborne infection. 


Background 


SARS-CoV-2 is very similar to the coronavirus RaTG13 detected in horseshoe bats. This raises the question if other animals can participate in a cross-species infection. If they are able to be infected, then animals could serve as a potential stockpile of the virus. The symptoms that appear in humans vary wildly, therefore efforts for vaccine trials must use an animal model that responds to the virus in a similar fashion to a human. 


Methods


Ferrets 


To test ferrets as potential animal models they took pairs of ferrets and infected them with two different viruses. One was collected from the environment of the proposed animal market origin in Wuhan china (F13-E) and the other from a patient (CTan-H). After 4 days the ferrets were euthanized and all portions of their bodies were analyzed using PCR. This test was repeated with several more pairs of ferrets measuring RNA, temperatures and other symptoms. Viral Samples were collected via a nasal swab.


Cats  


To test cats the researchers infected them using the (CTan-H) virus isolated from a human patient. The researchers also tested for the difference that age might have on infection location and intensity. The same methods were used on both sub adult cats (6-9 months) and juvenile cats (70-100 days). Viral RNA was measured from the fecal matter as nasal samples posed a danger to the researchers. Uninfected cats were also placed within the same incubator chamber as an infected cat. The infected and purposefully not infected cats could not physically interact, but they were breathing the same air. 


Dogs


To test dogs the researchers used five 3-month old beagles that were infected with (CTan-H) and housed with two purposefully uninfected beagles. Mouth and rectal tests were collected every two days for 14 days. Serum (portion of the blood) was collected from all the dogs on the 14th day. 



Results


Ferrets 


Only the respiratory tract showed any viral RNA for ferrets. All other portions of the ferret were either immune to infection or were simply undetectable via PCR. After doing some assay tests the researchers concluded that SARS-CoV-2 was able to bind and replicate inside the ferret's tonsils, nose, and soft palate. No virus was found within the lungs. 


Cats  


Both sub adult and juvenile cat groups showed infection that was present in the tonsils, lungs, small intestine, nasal passage, soft palate, and trachea, but no other organs. Specifically the juvenile cats had significant scarring of lung tissue. This led to the death of some juvenile cats within 4 days. Generally, older cats seemed to fare better than younger cats. The purposefully uninfected cats that were kept within the same incubator also showed viral RNA within their fecal matter after 4 days. Which indicates that cats are susceptible to airborne infection. 



Dogs


Only  2 of the infected dogs produced antibodies.  All of the purposefully uninfected dogs did not produce any antibodies in their blood. These results show that dogs have low susceptibility to SARS-CoV-2. 


Discussion 


Generally the researchers found that ferrets and cats are highly susceptible to SARS-CoV-2. Dogs have a low susceptibility, and other livestock including pigs, chickens, and ducks are not susceptible to the virus. Ferrets are commonly used as an animal model for the study of human respiratory diseases. Therefore, It is vital that the infection found in either humans or ferrets be incredibly similar. SARS-CoV-2 replicates in both the upper and lower respiratory tract in humans. However in ferrets it is exclusively confined to the nose, soft palate, and tonsils. It has also been noted with decreased frequency to replicate in the digestive tract, as viral RNA was found in the rectal swabs of the virus infected ferrets. However, no virus was found in any of the lung tissue in any ferret. Several studies report that SARS-CoV-2 uses a receptor known as angiotensin converting enzyme 2 (ACE2) to gain access to the cell. Cats and Ferrets have a two amino acid difference in the virus contacting regions of ACE2. Therefore, the mechanism that prevents replication of SARS-CoV-2 in the lower respiratory tract of ferrets still needs to be investigated. However, ferrets still remain a suitable animal model to test antiviral drugs or vaccines because SARS-CoV-2 is able to replicate efficiently in the upper respiratory tract.