Infection and Rapid Transmission of SARS-CoV-2 in Ferrets

Kim, Young Il; Kim, Seong Gyu; Kim, Se Mi; Kim, Eun Ha; Park, Su Jin; Yu, Kwang Min; Chang, Jae Hyung; Lee, Seunghun; Casel, Mark Anthony B.; Um, Jihye; Song, Min Suk; Jeong, Hye Won; Lai, Van Dam; Kim, Yeonjae; Chin, Bum Sik; Park, Jun-Sun; Chung, Ki Hyun; Foo, Suan Sin; Poo, Haryoung; Mo, In-Pil; Lee, Ok Jun; Webby, Richard J.; Jung, Jae U.; Choi, Young Ki

doi:10.1016/j.chom.2020.03.023

Cited by 903 publications

(1,172 citation statements)

References 21 publications

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“…SARS-CoV-2 transmission in experimental animal models has recently also been described by others. SARS-CoV-2 direct contact transmission between ferrets 21 and hamsters 22 was reported, with similar efficiency as observed in our study. In addition, SARS-CoV-2 was also found to be transmitted via the air in two out of six ferrets 21 , and in two out of six cats 23 .…”

Section: Figuresupporting

confidence: 91%

SARS-CoV-2 is transmitted via contact and via the air between ferrets

Richard

Kok

Meulder

et al. 2020

Preprint

130

190

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bioRxiv preprint SARS-CoV-2, a coronavirus that newly emerged in China in late 2019 1,2 and spread rapidly 12 worldwide, caused the first witnessed pandemic sparked by a coronavirus. As the pandemic 13 progresses, information about the modes of transmission of SARS-CoV-2 among humans is critical 14 to apply appropriate infection control measures and to slow its spread. Here we show that SARS-15 CoV-2 is transmitted efficiently via direct contact and via the air (via respiratory droplets and/or 16 aerosols) between ferrets. Intranasal inoculation of donor ferrets resulted in a productive upper 17 respiratory tract infection and long-term shedding, up to 11 to 19 days post-inoculation. SARS-18 CoV-2 transmitted to four out of four direct contact ferrets between 1 and 3 days after exposure 19 and via the air to three out of four independent indirect recipient ferrets between 3 and 7 days 20 after exposure. The pattern of virus shedding in the direct contact and indirect recipient ferrets 21 was similar to that of the inoculated ferrets and infectious virus was isolated from all positive 22 animals, showing that ferrets were productively infected via either route. This study provides 23 experimental evidence of robust transmission of SARS-CoV-2 via the air, supporting the 24 implementation of community-level social distancing measures currently applied in many 25 countries in the world and informing decisions on infection control measures in healthcare 26 settings 3 . In late December 2019, clusters of patients in China presenting with pneumonia of unknown etiology 29 were reported to the World Health Organization (WHO) 1 . The causative agent was rapidly identified 30 as being a virus from the Coronaviridae family, closely related to the severe acute respiratory 31 syndrome coronavirus (SARS-CoV) 2,4,5 . The SARS-CoV epidemic affected 26 countries and resulted in 32 more than 8000 cases in 2003. The newly emerging coronavirus, named SARS-CoV-2 6 , rapidly spread 33 worldwide and was declared pandemic by the WHO on March 11, 2020 7 . The first evidence 34 suggesting human-to-human transmission came from the descriptions of clusters among the early 35 cases 8,9 . Based on epidemiological data from China before measures were taken to control the 36 spread of the virus, the reproductive number R0 (the number of secondary cases directly generated 37 from each case) was estimated to be between 2 and 3 10-12 . In order to apply appropriate infection 38 control measures to reduce the R0, the modes of transmission of SARS-CoV-2 need to be elucidated.39 Respiratory viruses can be transmitted via direct and indirect contact (via fomites), and through the 40 air via respiratory droplets and/or aerosols. Transmission via respiratory droplets (> 5 μm) is 41 mediated by expelled particles that have a propensity to settle quickly and is therefore reliant on 42 close proximity between infected and susceptible individuals, usually within 1 m of the site of 43 expulsion. Transmission via aerosols (< 5 μm) is mediated by expelled parti...

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Section: Figuresupporting

confidence: 91%

SARS-CoV-2 is transmitted via contact and via the air between ferrets

Richard

Kok

Meulder

et al. 2020

Preprint

130

190

View full text Add to dashboard Cite

show abstract

“…However, the unphysiologically high expression level of ACE2 driven by the ubiquitous K14 promoter may not recapitulate the human disease caused by SARS-CoV-2. Recently, a ferret model of SARS-CoV-2 infection was established that mimics transmission and recapitulates aspects of human disease (Kim et al, 2020). Our study found that ACE2 from multiple species of laboratory animals, including but not limited to ferrets, crab-eating macaques, and Chinese hamsters could be utilized by SARS-CoV-2 to mediate viral infection.…”

Section: Discussionmentioning

confidence: 99%

“…ACE2 is expressed in a diverse range of species throughout the subphylum Vertebrata . Several recent studies demonstrated that ferrets, cats, dogs and some non-human primates are susceptible to SARS-CoV-2 (Kim et al, 2020; Lu et al, 2020; Rockx et al, 2020; Shi et al, 2020; Zhang et al, 2020a). However, the exact host tropism of SARS-CoV-2 remains unknown and is an urgent area to explore for identifying other putative zoonotic reservoirs.…”

Section: Introductionmentioning

confidence: 99%

Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals a Broad Potential Host Range of SARS-CoV-2

Liu

Wang

et al. 2020

Preprint

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The pandemic of a newly emerging coronavirus (SARS-CoV-2), the causative agent of severe pneumonia disease , is a major global health threat. Epidemiological studies suggest that bats are the natural zoonotic reservoir for SARS-CoV-2, however, the host range of SARS-CoV-2 and the identity of intermediate hosts that may facilitate the transmission to humans remains unknown. Coronavirus-receptor interaction is a key genetic determinant of the host range, cross-species transmission, and tissue tropism. SARS-CoV-2 uses Angiotensin-converting enzyme II (ACE2) as the receptor to enter its host cells in a species-dependent manner. It has been shown that human, palm civet, pig and bat ACE2 can support virus entry, while the murine ortholog cannot. In this study, we aimed to characterize ACE2 from diverse species for its ability to support viral entry. We found that ACE2 is expressed in a wide range of host species, with high conservation especially in mammals. By analyzing critical amino acid residues in ACE2 for virus entry, based on the well-characterized SARS-CoV spike protein interaction with ACE2 (human, bat, palm civet, pig and ferret ACE2), we identified approximately eighty ACE2 proteins from mammals could potentially function as the receptor to mediate SARS-CoV-2 entry. Functional assays showed that 44 of these mammalian ACE2 orthologs, including domestic animals, pet animals, livestock animals and even animals in the zoos or aquaria, could bind viral spike protein and support SARS-CoV-2 entry. In summary, our study demonstrates that ACE2 from a remarkably broad range of species support SARS-CoV-2 entry. These findings highlight a potentially broad host tropism and suggest that SARS-CoV-2 might be distributed much more widely than previously recognized, emphasizing the necessity to monitor the susceptible hosts, especially their potential of cross-species, which could prevent the future outbreaks.

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“…Since December of 2019, scientists all over the world have been working to establish animal model of COVID-19. So far there are several models reported in preprinted journals or peer-reviewed published journals, including two small murine models (hACE2 transgenic mouse 14 and Gold Syrian hamster 15 ), one ferret model 16 Retrospective studies of clinical features of COVID-19 show that older patients have more severe diseases, which may be associated with comorbidities, including tumor, diabetes, obesity, hypertension, heart diseases and so on [18][19][20] . These underlying diseases may make senior patients more susceptible to SARS-CoV-2 infection and worsen COVID-19.…”

Section: Sars-cov-2 Recently Reported As Another Novel Coronavirus Ementioning

confidence: 99%

Comparison of SARS-CoV-2 infections among 3 species of non-human primates

Zhao

et al. 2020

Preprint

149

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COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and new world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta, 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis, tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C.jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV2 infection, followed by M. fascicularis and C. jacchus. One Sentence Summary:M. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus.

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Infection and Rapid Transmission of SARS-CoV-2 in Ferrets

Cited by 903 publications

References 21 publications

SARS-CoV-2 is transmitted via contact and via the air between ferrets

SARS-CoV-2 is transmitted via contact and via the air between ferrets

Functional and Genetic Analysis of Viral Receptor ACE2 Orthologs Reveals a Broad Potential Host Range of SARS-CoV-2

Comparison of SARS-CoV-2 infections among 3 species of non-human primates

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