Abstract
Coronaviruses, which were generally considered harmless to humans before 2003, have appeared again with a pandemic threatening the world since December 2019 after the epidemics of SARS and MERS. It is known that transmission from person to person is the most important way to spread. However, due to the widespread host diversity, a detailed examination of the role of animals in this pandemic is essential to effectively fight against the outbreak. Although coronavirus infections in pets are known to be predominantly related to the gastrointestinal tract, it has been observed that there are human-to-animal transmissions in this outbreak and some animals have similar symptoms to humans. Although animal-to-animal transmission has been shown to be possible, there is no evidence of animal-to-human transmission.
Keywords: Animal, coronavirus, Covid-19, human, transmission
Introduction
Coronaviruses are included in the subfamily Orthocoronavirinae of the family Coronaviridae. The Orthocoronovirinaea subfamily is classified into four genera (Alpha-, Beta-, Gamma-, and Delta-coronaviruses) and a number of subgenera below these genera.[1–3] Coronaviruses are enveloped ribonucleic acid (RNA) viruses with a single chain and they do not contain RNA-dependent RNA polymerase enzymes but encode these enzymes in their genomes. They have rod-like extensions on their surfaces.[1,4] Due to receptor protrusions, high frequency of mutations, and RNA instabilities, they exhibit a wide host range and can be found in humans, bats, pigs, cats, dogs, rodents, and poultry.[1,5,6]
The first human coronavirus (HCoV) strain (HCoV-229E) was isolated from the nasal discharge of patients with a cold in the mid-1960s.[7] The strains of HCoV-229E and subsequent HCoV-OC43 have caused self-limiting, simple respiratory diseases.[8] Before 2003, it was widely accepted that coronavirus infections were generally harmless to humans. In 2003, SARS-CoV was registered as the cause of the first serious coronavirus outbreak with more than 8,000 people infected and a mortality rate of approximately 10%.[9,10] Ten years later, the Middle East respiratory syndrome (MERS) outbreak resulted in a permanent epidemic in the Arabian Peninsula and spread sporadically to the rest of the world.[11–13] Finally, the coronavirus disease (COVID-19) pandemic, caused by a novel coronavirus named SARS-CoV-2, broke out in China in December 2019, and it has been detected in more than 3,000,000 people till May 2020 and has caused more than 200,000 deaths.[14]
It is known that person-to-person transmission is the most important method of virus spread. However, to effectively fight this pandemic, which is considered a zoonotic disease, a detailed examination of the role of animals is essential.
COVID-19 disease in animals
Before the occurrence of the first highly pathogenic HCoV, SARS-CoV, there was little information about HCoVs, whereas extensive information about animal corona viruses, their evolution, and pathobiology is available. It is known that tissue tropisms and virulence evolve very quickly; they cause severe infectious diarrhea in dogs (canine coronavirus), pigs (porcine respiratory coronavirus and swine acute diarrhea syndrome coronavirus), and bats (porcine epidemic diarrhea virus and transmissible gastroenteritis virus), and infectious bronchitis attacks in some feline and poultry animals (infectious bronchitis virus and feline infectious peritonitis virus), and many medications are used for their treatment.[15–18]
Although, in terms of genome sequencing, SARS-CoV-2 showed 96.2% identity with the coronavirus (RaTG13) detected in horseshoe bats (Rhinolophus spp.) in Yunnan province in 2013, it was not previously observed in animals. As the first case in animals, a positive test result was reported in a Pomeranian dog on February 28, 2020, by the Hong Kong Agriculture, Fisheries and Conservation Department.[19] Subsequently, positive test results were reported in two dogs, two domestic cats, four tigers, and three lions.[20–22] Although dogs were asymptomatic, a domestic cat was found to have symptoms such as vomiting, diarrhea, and difficulty in breathing, and the tigers and lions had dry cough and wheezing.
In a study evaluating animals having close contact with people, it was shown that farm animals, including pigs, chickens, and ducks, were not susceptible to the virus. Dogs were poorly susceptible, but ferrets and especially young cats were very sensitive to SARS-CoV-2.[23] When macaques from non-human primates were examined, SARS-CoV-2 was shown to produce clinical and radiological findings similar to the picture in humans, especially in the elderly.[24,25]
In animal autopsies, appearances only involving the upper respiratory tract were observed in ferrets, but serious lesions were found in the nasal and tracheal mucosal epithelium and lungs in cats. Although viral RNA was observed in the intestinal organs, no significant histological changes were observed. It was observed that viral RNA was positive until the 11th day in the washing samples taken from the noses and soft palates of the cats and ferrets and in the feces of the cats, and until the 6th day in the dogs.[23]
COVID-19: Transmission from human to animal
Before the pandemic, SARS-CoV-2 was not observed in animals. The fact that the owner of the Pomeranian dog, which was reported as the first positive animal case, was found to be positive before raised the issue of human-to-animal transmission.[19] Subsequently, the tests of the owners of four dogs that were tested and a domestic cat with diarrhea and respiratory symptoms and positive test result were also positive.[20,26] The positive test result of the caretaker of the tigers, which were found positive in the zoo, strengthened the view that there was transmission from humans to animals.[27] Because such data have been increasing day by day, the World Organization of Animal Health has suggested that human-to-animal transmission may occur, and therefore, COVID-19 patients should limit contact with pets and other animals until more information about the virus is known.[28] All these suggest that the real effect of the disease can be felt for months beyond disease control.[29]
COVID-19: Transmission from animal to animal
It is known that SARS-CoV, the first serious coronavirus epidemic agent, can infect domestic cats, although data on dogs cannot be found, and transmission among them can occur even if symptoms do not develop.[30] Understanding the transmission potential of the SARS-CoV-2 virus from animal to animal due to its genome sequences and receptor properties similar to SARS-CoV is very important for effective strategies against the pandemic.[31] Preliminary studies showed that SARS-CoV-2 spread from cat to cat, and that specific neutralizing antibodies against this type of SARS-CoV-2 were produced.[23,32] In another study, viral RNA was found to be positive in all ferrets in the same cage with the virus incubated ferrets and in a few ferrets in the adjacent cage. Thus, it has been shown that animal-to-animal transmission by airway as well as by direct contact can occur.[33] This information raises the concern that there may be an increase in the number of people leaving their pets. Computer simulations have been performed to estimate how this may affect outbreak-related outcomes, and it has been anticipated that the number of animals to be abandoned may reveal significant differences in the risk of transmission.[34] It has been argued that quarantining animals at home would be a better strategy to control the spread of the virus.[35]
COVID-19: Transmission from animal to human
SARS-CoV-2 is considered to have been first transmitted from bats as the genome sequence was 96.2% identical to the coronavirus RaTG13 detected in horseshoe bats (Rhinolophus spp.) in Yunnan province in 2013. However, it is not yet known whether it was transmitted from bats to humans directly, or whether there was an intermediate host in the transmission.[36–39] In addition, there is no evidence yet to show that there is reverse zoonosis from animals to humans, which will cause the epidemic to become panzoonotic.[40] However, this potential public health concern requires further research.
Conclusion
It is known that transmission from person to person is the main route of spread in the SARS-CoV-2 pandemic. It is recommended that people who are sick should limit their contact with pets and other animals, and quarantine their pets at home, owing to the demonstration of human-to-animal and animal-to-animal transmissions. Animal-to-human transmission has not yet been demonstrated, but given the potential public health concern, health strategies need to be restructured comprehensively, not only during this outbreak but also in potential future outbreaks.
Main Points.
The role of animals in the spread of SARS-CoV-2 is examined in detail herein.
Occurrence of human-to-animal and animal-to-animal transmissions have been demonstrated.
Animal-to-human transmission has not been reported thus far.
Quarantining pets at home has been recommended.
It is recommended that health strategies be restructured to include animals.
Footnotes
Peer-review: This manuscript was prepared by the invitation of the Editorial Board and its scientific evaluation was carried out by the Editorial Board.
Author Contributions: Concept - A.K.; Design - S.G.; Supervision - A.K.; Data Collection and/or Processing - S.G.; Analysis and/or Interpretation - S.G.; Literature Search - M.K., Y.B., N.C.Ç.; Writing Manuscript - S.G.; Critical Review - A.K.
Conflict of Interest: The authors have no conflicts of interest to declare.
Financial Disclosure: The authors declared that this study has received no financial support.
References
- 1.Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al. Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses. Trends Microbiol. 2016;24:490–502. doi: 10.1016/j.tim.2016.03.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Wong LY, Lui PY, Jin DY. A molecular arms race between host innate antiviral response and emerging human coronaviruses. Virol Sin. 2016;31:12–23. doi: 10.1007/s12250-015-3683-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, et al. Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020;9:221–36. doi: 10.1080/22221751.2020.1719902. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Weiss SR, Navas-Martin S. Coronavirus pathogenesis and the emerging pathogen severe acute respiratory syndrome coronavirus. Microbiol Mol Biol Rev. 2005;69:635–64. doi: 10.1128/MMBR.69.4.635-664.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Li X, Song Y, Wong G, Cui J. Bat origin of a new human coronavirus: there and back again. Sci China Life Sci. 2020;63:461–2. doi: 10.1007/s11427-020-1645-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Su S, Wong G, Shi W, Liu J, Lai ACK, Zhou J, et al. Epidemiology, genetic recombination, and pathogenesis of coronaviruses. Trends Microbiol. 2016;24:490–502. doi: 10.1016/j.tim.2016.03.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kendall EJ, Bynoe ML, Tyrrell DA. Virus isolations from common colds occurring in a residential school. Br Med J. 1962;2:82–6. doi: 10.1136/bmj.2.5297.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.New respiratory virus. Br Med J. 1967;3:752. doi: 10.1136/bmj.3.5568.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Cheng VC, Lau SK, Woo PC, Yuen KY. Severe acute respiratory syndrome coronavirus as an agent of emerging and reemerging infection. Clin Microbiol Rev. 2007;20:660–94. doi: 10.1128/CMR.00023-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, et al. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003;361:1319–25. doi: 10.1016/S0140-6736(03)13077-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814–20. doi: 10.1056/NEJMoa1211721. [DOI] [PubMed] [Google Scholar]
- 12.Hilgenfeld R, Peiris M. From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses. Antiviral Res. 2013;100:286–95. doi: 10.1016/j.antiviral.2013.08.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Gao H, Yao H, Yang S, Li L. From SARS to MERS: evidence and speculation. Front Med. 2016;10:377–82. doi: 10.1007/s11684-016-0466-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.WHO Coronavirus disease (COVID-2019) situation reports-102. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
- 15.Decaro N, Lorusso A. Novel human coronavirus (SARS-CoV-2): a lesson from animal coronaviruses. Vet Microbiol. 2020;244:108693. doi: 10.1016/j.vetmic.2020.108693. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Decaro N, Mari V, Campolo M, Lorusso A, Camero M, Elia G, et al. Recombinant canine coronaviruses related to transmissible gastroenteritis virus of swine are circulating in dogs. J Virol. 2009;83:1532–7. doi: 10.1128/JVI.01937-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Lorusso A, Decaro N, Schellen P, Rottier PJ, Buonavoglia C, Haijema BJ, et al. Gain, preservation, and loss of a group 1a coronavirus accessory glycoprotein. J Virol. 2008;82:10312–7. doi: 10.1128/JVI.01031-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Addie DD, Curran S, Bellini F, Crowe B, Sheehan E, Ukrainchuk L, et al. Oral Mutian® X stopped faecal feline coronavirus shedding by naturally infected cats. Res Vet Sci. 2020;130:222–9. doi: 10.1016/j.rvsc.2020.02.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.AFCD. Detection of low level of COVID-19 virus in pet dog. [accessed 24 March 2020]. Available from: www.afcd.gov.hk/english/publications/publications_press/pr2335.html.
- 20.The Government of the Hong Kong Special Administrative Region - Press Releases. Pet dog tests positive for COVID-19 virus. 2020a. [cited 2020 Apr 1]. Available from: https://www.info.gov.hk/gia/general/202003/19/P2020031900606.htm.
- 21.The Government of the Hong Kong Special Administrative Region - Press Releases. Pet dog further tests positive for antibodies for COVID-19 virus. 2020b. [cited 2020 Apr 1]. Available from: https://www.info.gov.hk/gia/general/202003/26/P2020032600756.htm.
- 22.The Government of the Hong Kong Special Administrative Region - Press Releases. Pet cat tests positive for COVID-19. 2020c. [cited 2020 Feb 4]. Available from: https://www.info.gov.hk/gia/general/202003/31/P2020033100717.htm.
- 23.Shi J, Wen Z, Zhong G, Yang H, Wang C, Huang B, et al. Susceptibility of ferrets, cats, dogs, and different domesticated animals to SARS coronavirus 2. Science. 2020 doi: 10.1126/science.abb7015. doi: 10.1126/science.abb7015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Rockx B, Kuiken T, Herfst S, Bestebroer T, Lamers MM, Oude Munnink BB, et al. Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model. Science. 2020 doi: 10.1126/science.abb7314. doi: 10.1126/science.abb7314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Yu P, Qi F, Xu Y, Li F, Liu P, Liu J, et al. Age-related rhesus macaque models of COVID-19. Animal Model Exp Med. 2020;3:93–7. doi: 10.1002/ame2.12108. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.The Brussels Times. Coronavirus: Belgian woman infected her cat. Available from: https://www.brusselstimes.com/all-news/belgium-allnews/103003/coronavirus-belgian-woman-infected-her-cat/
- 27.USDA Statement on the Confirmation of COVID-19 in a Tiger in New York. Available from: https://www.aphis.usda.gov/aphis/newsroom/news/sa_by_date/sa-2020/ny-zoo-covid-19.
- 28.World Organisation for Animal Health (WOAH) Questions and Answers on the 2019 Coronavirus Disease (COVID-19) [Accessed March 9, 2020]. Available from: https://www.oie.int/en/scientific-expertise/specific-information-and-recommendations/questions-and-answers-on-2019novel-coronavirus/
- 29.Ho HC, Hughes T, Bozlu M, Kadıoğlu A, Somani BK. What do urologists need to know: Diagnosis, treatment, and follow-up during COVID-19 pandemic. Turk J Urol. 2020;46:169–77. doi: 10.5152/tud.2020.20119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Martina BE, Haagmans BL, Kuiken T, Fouchier RAM, Rimmelzwaan GF, Van Amerongen G, et al. Virology: SAR S virus infection of cats and ferrets. Nature. 2003;425:915. doi: 10.1038/425915a. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395:565–74. doi: 10.1016/S0140-6736(20)30251-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Zhang Q, Zhang H, Huang K, Yang Y, Hui X, Gao J, et al. SARS CoV 2 neutralizing serum antibodies in cats: a serological investigation [Internet] Wuhan. 2020 Available from: https://www.biorxiv.org/content/10.1101/2020.04.01.021196v1 https://doi.org/10.1101/2020.04.01.021196. [Google Scholar]
- 33.Kim YI, Kim SG, Kim SM, Kim EH, Park SJ, Yu KM, et al. Infection and Rapid Transmission of SARS-CoV-2 in Ferrets. Cell Host Microbe. 2020 doi: 10.1016/j.chom.2020.03.023. doi: 10.1016/j.chom.2020.03.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Gao T, Pan X, Pan C. The fate of house cats during the COVID-19 pandemic. Microbes Infect. 2020 doi: 10.1016/j.micinf.2020.04.006. pii: S1286-4579(20)30073-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Science News. Available from: https://www.sciencemag.org/news/2020/03/quarantine-cat-disinfect-dog-latest-advice-about-coronavirus-and-your-pets.
- 36.Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270–3. doi: 10.1038/s41586-020-2012-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Cyranoski D. Mystery deepens over animal source of coronavirus. Nature. 2020;579:18–9. doi: 10.1038/d41586-020-00548-w. [DOI] [PubMed] [Google Scholar]
- 38.Singhal T. A Review of Coronavirus Disease-2019 (COVID-19) Indian J Pediatr. 2020;87:281–6. doi: 10.1007/s12098-020-03263-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Guo YR, Cao QD, Hong ZS, Tan YY, Chen SD, Jin HJ, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res. 2020;7:11. doi: 10.1186/s40779-020-00240-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.First case human-to-dog transmission in Hong Kong. Available from: https://www.livescience.com/coronavirus-first-case-human-to-dog-transmission.html.
