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

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          Summary

          The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China and rapidly spread worldwide. To prevent SARS-CoV-2 dissemination, understanding the in vivo characteristics of SARS-CoV-2 is a high priority. We report a ferret model of SARS-CoV-2 infection and transmission that recapitulates aspects of human disease. SARS-CoV-2-infected ferrets exhibit elevated body temperatures and virus replication. Although fatalities were not observed, SARS-CoV-2-infected ferrets shed virus in nasal washes, saliva, urine, and feces up to 8 days post-infection. At 2 days post-contact, SARS-CoV-2 was detected in all naive direct contact ferrets. Furthermore, a few naive indirect contact ferrets were positive for viral RNA, suggesting airborne transmission. Viral antigens were detected in nasal turbinate, trachea, lungs, and intestine with acute bronchiolitis present in infected lungs. Thus, ferrets represent an infection and transmission animal model of COVID-19 that may facilitate development of SARS-CoV-2 therapeutics and vaccines.

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          Highlights

          • •

            SARS-CoV-2-infected ferrets exhibit elevated body temperature and virus replication

          • •

            SARS-CoV-2 is shed in nasal washes, saliva, urine and feces

          • •

            SARS-CoV-2 is effectively transmitted to naive ferrets by direct contact

          • •

            SARS-CoV-2 infection leads acute bronchiolitis in infected ferrets

          Abstract

          The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spreads, leading to a pandemic infection. Kim et al. show that ferrets are highly susceptible to SARS-CoV-2 infection and effectively transmit the virus by direct or indirect contact, recapitulating human infection and transmission.

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Na Zhu, Dingyu Zhang, Wenling Wang … (2020)
          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
          Article 0 comments Cited 12882 times – based on 0 reviews     Review now
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            Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

            Roujian Lu, Xiang Zhao, Juan Li … (2021)
            Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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              Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

              Theo M. Bestebroer, Albert Osterhaus, Sander van Boheemen … (2012)
              A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
              Article 0 comments Cited 3061 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Jae U. Jung
                Young Ki Choi
                Journal
                Journal ID (nlm-ta): Cell Host Microbe
                Journal ID (iso-abbrev): Cell Host Microbe
                Title: Cell Host & Microbe
                Publisher: Published by Elsevier Inc.
                ISSN (Print): 1931-3128
                ISSN (Electronic): 1934-6069
                Publication date PMC-release: 6 April 2020
                Publication date (Electronic): 6 April 2020
                Affiliations
                [1 ]College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea
                [2 ]Zoonotic Infectious Diseases Research Center, Chungbuk National University, Cheongju, Republic of Korea
                [3 ]College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
                [4 ]Research institute of Public Health, National Medical Center, Seoul, Republic of Korea
                [5 ]Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
                [6 ]Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, University of Science and Technology, Daejeon, Republic of Korea
                [7 ]Division of Virology, Department of Infectious Diseases, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
                Author notes
                [∗ ]Corresponding author jaeujung@ 123456med.usc.edu
                [∗∗ ]Corresponding author choiki55@ 123456chungbuk.ac.kr
                [8]

                Lead Contact

                Article
                Publisher ID: S1931-3128(20)30187-6
                DOI: 10.1016/j.chom.2020.03.023
                PMC ID: 7144857
                PubMed ID: 32259477
                SO-VID: f8a5cd38-dd3f-4a1a-b656-2363106f7782
                Copyright © © 2020 Published by Elsevier Inc.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 27 February 2020
                Date revision received : 16 March 2020
                Date accepted : 27 March 2020
                Categories
                Subject: Article

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: 2019-novel coronavirus,2019-ncov,severe acute respiratory syndrome coronavirus 2,sars-cov-2,novel coronavirus disease,covid-19,virus shedding,transmission,ferrets
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: 2019-novel coronavirus, 2019-ncov, severe acute respiratory syndrome coronavirus 2, sars-cov-2, novel coronavirus disease, covid-19, virus shedding, transmission, ferrets

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