The new coronavirus is thought to originate from bats, and it has 96.2% similarity in nucleotide sequence level with RaTG13 from Chinese chrysanthemum head coronavirus RaTG13 (collected by the research team of Shi Zhengli, Wuhan Institute of Virology, Chinese Academy of Sciences, Yunnan, China in 2013) This is a new type of coronavirus that has not been detected in humans and other animals before. Its emergence brings a lot of problems to be solved, including whether there are pets, livestock and poultry other than humans. It may also be infected by the new coronavirus?

On April 8, local time, the top academic journal “Science” published the paper “Susceptibility of ferrets, cats, dogs, and different domestic animals to SARS -coronavirus-2 “. This study aims to clarify some questions: Will the new coronavirus be transmitted to other animal species and become a “reservoir” of infection? Neocoronavirus infection has multiple clinical manifestations in humans, from mild infection to death, so how does it manifest in other animals? With the development of vaccines and antiviral drugs, which animals can be used to most accurately simulate the effects of these drugs or vaccines on humans?


To solve these problems, from the State Key Laboratory of Veterinary Biotechnology, National Animal Science, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences The research team of the high-level biosecurity laboratory for epidemic prevention and control evaluated the susceptibility of different models of experimental animals, pets, livestock and poultry to the new coronavirus. Through the experimental infection of the new coronavirus, the clinical manifestations and pathological changes of the inoculated animals and cohabiting animals were observed and detected. Viral load of organs and tissues, respiratory and enterovirus emissions, and the positive of antibodies against neocoronavirus in animals.

Their research shows that the new coronavirus has very weak replication ability in dogs, pigs, chickens and ducks, but it can be used in the upper respiratory tract of ferrets and the respiratory system and digestion of cats The system replicates efficiently. Experimentally infected cats can transmit the new coronavirus through the air; some cats can cause severe morbidity or even death after infection, and the incidence of young cats is obviously more serious than that of older cats.

Histopathological observations confirmed that viral infection of cats can cause different degrees of lung inflammation and intestinal mucosal damage; immunohistochemical studies have found mucosal epithelium of upper respiratory tract (nasal cavity, palate, tonsils) and olfactory bulb cells, trachea And bronchial mucosal mucosal gland epithelial cells, small intestinal mucosal epithelium and other parts of the virus infection.

The corresponding author of this paper is the academician of the Chinese Academy of Sciences, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences Chen Hualan, Chief Scientist of Animal Influenza Basic and Prevention Research Innovation Team, Director of Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, Director of National Animal Disease Prevention and Control High-level Biosafety Laboratory Bu Zhigao, and Secretary of Party Committee of China Center for Disease Control and Prevention Wu Guizhen, Director of the BSL-3 Laboratory. Prior to March 31, local time, the research team had taken the lead in publishing the study on the preprint platform bioRxiv.

Worth It is mentioned that the National Animal Disease Prevention and Control High-level Biosafety Laboratory is China ’s two existing P4 (Biosafety Level 4 ) One of the laboratories, and the other is in the Wuhan National Biosafety Laboratory of the Chinese Academy of Sciences. All the experiments on the infection of the new coronavirus in this study were conducted in the P4 laboratory with the approval of the Ministry of Agriculture and Rural Affairs of China. Animal Research and Animal Welfare Program Approved by the Animal Experiment Ethics Committee of the Chinese Academy of Agricultural Sciences.

The press release issued by the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences mentioned in the press release that there have always been mammals and poultry Different coronaviruses are prevalent, but most of these coronaviruses are limited to infecting specific species of animals and generally cannot infect humans. Similarly, several common coronaviruses in humans do not infect other animals. However, certain coronaviruses from bats, such as SARS and Middle East Respiratory Syndrome (MERS) viruses can often infect a variety of animals and humans.

The new coronavirus is currently prevalent in a large number of people around the world. The risk of human beings in close contact with animals is increasing day by day. Therefore, there is an urgent need to study the susceptibility of domestic animals to new coronavirus in close contact with humans Evaluate whether domestic animals face the risk of new coronavirus and become a potential intermediate host to provide a scientific basis for the prevention and control of new coronavirus.

In addition, given the current global prevalence of COVID-19 , It is likely to evolve into common infectious diseases, and it is urgent to establish a stable and reliable animal infection model to meet the needs of vaccine and drug research and development evaluation.

The research team emphasizes , Surveillance of feline neocoronavirus should be regarded as a way to eliminate the current prevalence of COVID-19Kinds of auxiliary means. They called for close monitoring and protection of cats in the affected area to avoid contact with the source of infection and prevent them from becoming possible hosts for transmission or storage.

In addition, there have been questions about the cat ’s infection with the new crown because of the large doses under laboratory conditions. However, in addition to this research, before April 3, the State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Professor of the College of Veterinary Medicine, Academician Jin Meilin, Director of the Key Laboratory of Veterinary Diagnostic Preparations of the Ministry of Agriculture, Wuhan Institute of Virus Research, Chinese Academy of Sciences The team led by researcher Shi Zhengli, director of the Institute of Infectious Diseases Research Center of the Institute and director of the Key Laboratory of Pathogenic Biology and Biosecurity of the Chinese Academy of Sciences, also published a study on the preprint platform bioRxiv. They found through cat serum survey: Wuhan Serum ELISA detection of 102 cats collected after the outbreak of the new crown epidemic in the region showed that sera from 15 cats (14.7%) were positive for the receptor binding domain (RBD) of the new crown virus.

The 4-year-old tiger Malayan tiger Nadia of the Bronx Zoo in New York, USA was also diagnosed with new coronavirus recently. On April 5, local time, the US Department of Agriculture issued a statement confirming that a tiger in a New York zoo was diagnosed with the new coronavirus, and several other lions and tigers also showed symptoms of respiratory diseases. The New York Bronx Zoo official stated that Nadia and three other tigers and three African lions had symptoms of dry cough and decreased appetite, but they are expected to recover. Public health officials believe that the animals were infected by an asymptomatic employee.


New coronavirus can replicate in the upper respiratory tract of ferrets for up to 8 days, but will not cause serious illness or death

ferrets are often used Animal model of human respiratory virus. Therefore, the research team first tested the sensitivity of the ferret to the new coronavirus.

Two new coronavirus strains were used in this study: F13-E from the South China Seafood Market in Wuhan and CTan-H from a patient infected with the new coronavirus.

The research team inoculated 10 ^ 5pfu (plaque forming unit) F13-E or CTan-H intranasally to ferrets, and implemented it on the 4th day after inoculation Euthanasia (pi). The turbinate, soft palate, tonsils, trachea, lung, heart, spleen, kidney, pancreas, small intestine, brain, and liver of each ferret were collected, and viral RNA was determined by qPCR and virus titration.


Viral RNA in ferret organs or tissues: A, F13-E, B, CTan-H.

The research results show that viral RNA and infectious virus have been detected in the turbinates, soft palate and tonsils of all 4 ferrets, but in other detection organizations None of them are seen.


C, virus drops in ferret organs or tissues inoculated with F13-E, D, CTan-H degree.

The research team believes that these results indicate that the new coronavirus can replicate in the upper respiratory tract of ferrets, but no replication has been detected in other tissues.

In order to study the replication dynamics of the virus in ferrets, the research team inoculated 6 ^ ferrets intranasally with 10 ^ 5pfu of F13-E (3) or CTan-H (3 animals), then place them in three separate cages that are separated and separated. Ferret nasal washes and rectal swabs were collected on days 2, 4, 6, 8 and 10 for viral RNA detection and virus titration. At the same time, they were monitored for body temperature and signs of new crowns for two weeks.


Inoculated with F13-E (E) and CTan-H (F) viral RNA in the ferret nasal washes. Inoculated F13 -E (G) and CTan-H (H) virus titers in ferret nasal washes.

The results show that the second and fourth On days 6, 6, and 8, viral RNA was found in the nasal washes of all six ferrets. Viral RNA was also found in some rectal swabs, but the copy number was significantly lower than that of nasal washes. Infectious virus was detected in the liquid, but no infectious virus was found in the rectal swab of a ferret.

Each group of ferrets inoculated with virus One had fever and loss of appetite on days 10 and 12. To investigate whether these symptoms were caused by virus replication in the lower respiratory tract, the research team euthanized the two ferrets on day 13 and collected their organs Perform viral RNA detection.

However, except for low copy numbers detected in CTan-H-inoculated ferret turbinates, no virus was detected in any other tissues or organs RNA.

Pathological studies showed that in the two ferrets euthanized on the 13th day, there were severe lymphoplasmacytic periangiitis and vasculitis, alveolar septa and type II alveoli in the alveolar space The number of cells, macrophages and neutrophils increased, and there was mild peribronchitis in the lungs.


The asterisk indicates that the animal is euthanized on the 13th day after the virus is inoculated, and the remaining 4 are on the 20th day. Animals are euthanized.

Through ELISA and neutralization test, new coronavirus antibodies were detected in all ferrets, including antibody drops of two ferrets euthanized on day 13 The degree is significantly lower than that of the ferret who was euthanized on the 20th day.

In order to further study the newWhether the coronavirus replicated in the lungs of the ferret, the research team inoculated 10 ^ 5 pfu of CTan-H intratracheally to 8 ferrets, and euthanized 2 animals on days 2, 4, 8 and 14, respectively. Detection of viral RNA in tissues and organs.

In the two ferrets who were euthanized on the second day and the two ferrets that were euthanized on the fourth day, the researchers were only in one of them Viral RNA was detected in the medium; among the two ferrets that were euthanized on day 8, viral RNA was detected in the soft palate of one ferret and viral RNA was detected in the turbinate, soft palate, tonsils and trachea of ​​the other ferret; No viral RNA was detected in the two ferrets that were euthanized on day 14.

These results show that the new coronavirus can replicate in the upper respiratory tract of ferrets for up to 8 days without causing serious illness or death.

The research team also mentioned at the end of the paper that, in comparison, the new crown virus and other influenza viruses that can replicate in the upper and lower respiratory tracts of ferrets, even human SARS-CoV shows some differences. The new coronavirus only replicates in the nasal bones, soft palate and tonsils of ferrets. It can also replicate in the digestive tract, but even if the virus is inoculated in the trachea, no virus has been detected in the lobes of the ferret.


Cats are highly susceptible and “inter-cat spread” occurs: the monitoring of feline new coronavirus should be regarded as an auxiliary means of epidemic prevention and control It is because cats and dogs have close contact with humans, so the research team believes that in addition to laboratory animals such as ferrets, it is important to understand the susceptibility of domestic animals that often live with humans to the new coronavirus for the control of COVID-19.

The research team first studied the replication of the new coronavirus in cats. Five 8-month-old sub-adult domestic cats (outbred strains) were intranasally inoculated with 10 ^ 5 pfu of CTan-H, of which 2 cats planned to be euthanized on the 6th day to evaluate the virus replication in their organs . 3 cats were placed in separate cages inside the isolator. To monitor the spread of respiratory droplets, an uninfected cat was placed in a cage adjacent to each virus-inoculated cat.

As 8-month-old cats are aggressive, it is difficult to routinely clean them. To avoid possible harm, the research team collected the feces of these cats and examined the viral RNA in their organs after euthanasia.


Two sub-adult domestic cats euthanized on day 6 were detected in the nasal bones, soft palate and tonsils Viral RNA was also detected in one of the trachea and the other small intestine. However, no viral RNA was detected in any lung samples of these two cats.

Infectious viruses were detected in the viral RNA-positive nasal bones, soft palate, tonsils and trachea of ​​these cats, but no infectious viruses were found in the viral RNA-positive small intestine .


The spread of new coronavirus between cats.

In the virus transmission study, RNA virus was detected in the feces of two vaccinated cats on the third day, and all three vaccinated cats on the fifth day RNA viruses were detected in the stool. Viral RNA was detected on the feces of one of the three cats at risk of virus exposure.

Viral cats vaccinated with viral RNA positive feces were euthanized on the 11th day. The soft palate and tonsils of the virus-inoculated cats, and the nasal bones, soft palate, and tonsils of the cats exposed by the virus Viral RNA was detected in the trachea, indicating that respiratory droplets have spread between cats.

On the 12th day, the research team euthanized the remaining cats. Viral RNA was detected in the tonsils of a virus-inoculated cat, and in the nasal bone, soft palate, tonsils, and trachea of ​​another virus-inoculated cat, but was not detected in any organs or tissues of the two virus-exposed cats disease