This post was reviewed by Dr. Scott Covey, one of our subject matter experts.
Summary of today’s paper:
In this paper published in Science, scientists from the China Center for Disease Control and Prevention examine how well SARS-CoV-2 can transmit to and infect lab animal models, our companion pets, and farm animals. This is an important question to look into as it can provide insight into appropriate animal models for SARS-CoV-2 research. Beyond this, the research may provide clues on how to manage animal-human contact to avoid spreading COVID-19 further. By performing their experiments, these scientists found that ferrets and cats are susceptible to SARS-CoV-2 infection and can transmit the virus to each other. They also found that SARS-CoV-2 can’t replicate that well in dogs, pigs, chickens, and ducks, nor can it transmit well between them.
The paper we will be demystifying today can be found here, if you’d like to follow along.
Hailing from China Centre for Disease Control, the Harbin Veterinary Research institute, and the National High Containment Laboratory of Animal Diseases Control and Prevention, this group of researchers investigated whether SARS-CoV-2 can transmit from and replicate in animals that are in close contact with humans. This paper helps provide some insight on what a good animal model to study SARS-CoV-2 could be and determine how well possible vaccines work. This research also provides some guidance on animal management for controlling the spread of SARS-CoV-2 and COVID19 (the disease caused by SARS-CoV-2).
The researchers stated that SARS-CoV-2 genome has been determined to be 96.2% similar to another coronavirus, RaTG13, which was detected in horseshoe bats back in 2013. Interestingly, RaTG13 has not been detected in any other animals (or humans). In the case of SARS-CoV-2, the researchers knew that infection of SARS-CoV-2 presents a large range of clinical and disease manifestations in humans. However, what they (and we) didn’t know was how this particular virus behaves in other animals.
This is an important question as many other scientists around the world are working on vaccines and antiviral drugs. In order to test these treatment options, scientists and researchers need to know how to precisely model and measure how the drugs would work in model organisms before testing in humans. Towards this these researchers decided that they’ll look at how SARS-CoV-2 can infect laboratory animals, like ferrets, and our companion and domesticated animals, like cats and chickens.
In pigs, ducks and chickens there was no evidence of infection or disease. In dogs, viral RNA and antibodies to SARS-CoV2 were found in some of the dogs (may want to add actual numbers). However, no infectious virus was found in any of the dogs. This indicates that dogs may have a low susceptibility to the virus. They did find that this virus can infect and replicate in ferrets and cats. But cats are much more susceptible to infection by virus particles in the air. How did they come to this conclusion?
Well, 2 strains of SARS-CoV-2 were used in their experiments. The first strain was an environmental sample collected from the Huanan Seafood Market in Wuhan named SARS-CoV-2/F13/environment/2020/Wuhan (F13-E). The second strain was isolated from a human patient and was called SARS-CoV-2/CTan/human/2020/Wuhan (CTan-H).
First, ferrets were tested for susceptibility of SARS-CoV-2 (susceptibility means whether a virus is able to enter a cell). They gave a specific dose of the F13-E strain to 1 pair of ferrets and the CTan-H strain to another pair of ferrets. After the ferrets were infected for 4 days, organs were collected to determine how much SARS-CoV-2 viral RNA was present. This was performed using reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) along with a virus titration in Vero E6 cells.
This led to the discovery that that infectious SARS-CoV-2 (of both strains) was found in the nasal turbinate (an organ that helps keep the air warm and moist in the nose), soft palate, and tonsils but not in the other organs they tested. This clearly indicated to the researchers that SARS-CoV-2 can replicate in the upper respiratory tract in ferrets and that replication of this virus couldn’t be detected in other organs.
So, now that they knew this, the researchers wanted to look at the dynamics of how SARS-CoV-2 replicates in ferrets. They did this by infecting ferrets with one of the two strains of the SARS-CoV-2 virus and collecting nasal and rectal swabs (sort of like when we do swabs to test for SARS-CoV-2) for several days to see what would happen. This led them to find out that infectious virus was detected in high numbers in the nasal swabs but not in the rectal swabs. They did notice some symptoms. The ferrets developed fevers and had a loss in appetite after 10-12 days, but they were not able to determine whether this was caused by SARS-CoV-2 infection.
Antibodies for SARS-CoV-2 were detected in all ferrets they tested. The researchers also did in vitro tests and determined that SARS-CoV-2 could attach to bronchiolar epithelial cells. These cells are found in the lower respiratory tract. However, in vivo experiments in ferrets saw that SARS-CoV-2 could infect and replicate in cells in the upper respiratory tract.
So that’s cool, but what about the cats and dogs that we consider our fur babies and friends? To actually test the cats, they infected a few subadult cats as well as looked at whether naïve (uninfected) cats exposed to an infected cat can get sick. It is important to note that all the cats were physically separate, but they shared the same air. In doing so, they found that after about 3 days, a few cats did get infected from their infected neighbors. This clearly meant that respiratory transmission is possible between our feline friends.
Now to collect samples from the exposed uninfected cats, the researchers couldn’t do swabs because the cats were not happy and scratched a lot. So, instead they looked at fecal samples and collected organs after death. This revealed that in exposed cats, the virus was detectable in the organs of the upper and lower respiratory tract.
When they looked at young kitties, they saw that SARS-CoV-2 causes massive lesions in the nasal and tracheal mucus epithelium and in the lungs. This showed the scientists that the cells in younger cats are much more permissive to infection and that SARS-CoV-2 is more efficient in replicating. For those who don’t know, permissive cells are cells that allow a virus to take over its resources.
In dogs that were infected with the CTan-H SARS-CoV-2 strain, they detected viral RNA in rectal swabs. But when they looked in the organs, they didn’t detect any viral RNA. They also looked at antibody development in the dogs and saw that most dogs were tested negative for SARS-CoV-2. This showed the scientists that SARS-CoV-2 can’t really infect dogs that well.
But what about pigs, chickens, and ducks? Well, using the same experimental setup as they did with the dogs, they saw that viral RNA was not detected in any swabs that they collected. Antibody testing in these animals was also all negative. So, like dogs, SARS-CoV-2 can’t really infect these animals that well.
So, all of these experiments did show these researchers a few things. One, that unlike other coronaviruses, SARS-CoV-2 only appears to infect and replicate in the upper respiratory tract in ferrets. There are some suggestions that this virus could also replicate in the digestive tract (because viral RNA was found in the rectal swabs). However, more experiments will have to be done to show this.
Based on their findings, the researchers suggest that we should also start to test cats for SARS-CoV-2. The researchers believe this will help us ensure that we can eliminate COVID-19 in humans. All that aside, the main thing this paper shows is that ferrets are an ideal animal model organism. This could potentially be a crucial finding for drug and vaccine development and testing.
