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      SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters

      research-article
      1 , 2 , 3 , 1 , 3 , 4 , 4 , 4 , 5 , 6 , 7 , 8 , 4 , 4 , 4 , 4 , 9 , 8 , 3 , 2 , 3 , 1 , 3 , 10 , 6 , 7 , 9 , 11 , 3 , 11 , 11 , 12 , 13 , 13 , 9 , 13 , 14 , 8 , 15 , 15 , 14 , 11 , 8 , 4 , 16 , 16 , 16 , 16 , 16 , 16 , 17 , 18 , 6 , 7 , 19 , 17 , 6 , 17 , 18 , 20 , Consortium Mount Sinai Pathogen Surveillance (PSP) study group, 9 , 9 , 4 , 3 , 10 , 3 , 10 , 3 , 10 , 15 , 16 , 9 , 8 , 21 , 6 , 7 , 18 , 20 , 22 , 6 , 7 , 2 , 4 , 23 , 24 , , 4 , 23 , 24 , 25 , , 1 , 3 , 10 ,
      Nature
      Nature Publishing Group UK
      Pathogens, SARS-CoV-2

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          Abstract

          The recent emergence of B.1.1.529, the Omicron variant 1, 2 , has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs.  3, 4 ), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

          Abstract

          A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.

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          Most cited references47

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          Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

          The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.
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            Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

            Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.
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              CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV)

              In this retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed, with emphasis on identifying and characterizing the most common findings. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities. © RSNA, 2020
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                Author and article information

                Contributors
                jboon@wustl.edu
                mdiamond@wustl.edu
                yoshihiro.kawaoka@wisc.edu
                Journal
                Nature
                Nature
                Nature
                Nature Publishing Group UK (London )
                0028-0836
                1476-4687
                21 January 2022
                21 January 2022
                2022
                : 603
                : 7902
                : 687-692
                Affiliations
                [1 ]GRID grid.14003.36, ISNI 0000 0001 2167 3675, Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, , University of Wisconsin-Madison, ; Madison, WI USA
                [2 ]GRID grid.410795.e, ISNI 0000 0001 2220 1880, Department of Pathology, , National Institute of Infectious Diseases, ; Tokyo, Japan
                [3 ]GRID grid.26999.3d, ISNI 0000 0001 2151 536X, Division of Virology, , Institute of Medical Science, University of Tokyo, ; Tokyo, Japan
                [4 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Medicine, , Washington University School of Medicine, ; St Louis, MO USA
                [5 ]GRID grid.14003.36, ISNI 0000 0001 2167 3675, Department of Surgical Sciences, School of Veterinary Medicine, , University of Wisconsin–Madison, ; Madison, WI USA
                [6 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Department of Microbiology, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [7 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Global Health and Emerging Pathogens Institute, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [8 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory Vaccine Center, , Emory University School of Medicine, ; Atlanta, GA USA
                [9 ]GRID grid.94365.3d, ISNI 0000 0001 2297 5165, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, , National Institutes of Health, ; Bethesda, MD USA
                [10 ]GRID grid.45203.30, ISNI 0000 0004 0489 0290, The Research Center for Global Viral Diseases, , National Center for Global Health and Medicine Research Institute, ; Tokyo, Japan
                [11 ]GRID grid.53857.3c, ISNI 0000 0001 2185 8768, Department of Animal Dairy, and Veterinary Sciences, College of Agriculture and Applied Sciences, , Utah State University, ; Logan, UT USA
                [12 ]GRID grid.28803.31, ISNI 0000 0001 0701 8607, Department of Pathobiological Sciences, School of Veterinary Medicine, , University of Wisconsin, ; Madison, WI USA
                [13 ]GRID grid.10689.36, ISNI 0000 0001 0286 3748, Colombia/Wisconsin One-Health Consortium and One-Health Genomic Laboratory, , Universidad Nacional de Colombia, ; Medellín, Colombia
                [14 ]GRID grid.14003.36, ISNI 0000 0001 2167 3675, Wisconsin State Laboratory of Hygiene, ; Madison, WI USA
                [15 ]GRID grid.214572.7, ISNI 0000 0004 1936 8294, Department of Microbiology and Immunology, , University of Iowa, ; Iowa City, IA USA
                [16 ]GRID grid.240871.8, ISNI 0000 0001 0224 711X, Department of Infectious Diseases, , St Jude Children’s Research Hospital, ; Memphis, Tennessee USA
                [17 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Department of Genetics and Genomic Sciences, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [18 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Department of Pathology, Molecular and Cell-Based Medicine, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [19 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Graduate School of Biomedical Sciences, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [20 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, Department of Medicine, Division of Infectious Diseases, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [21 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Department of Microbiology and Immunology, , Emory University, ; Atlanta, GA USA
                [22 ]GRID grid.59734.3c, ISNI 0000 0001 0670 2351, The Tisch Cancer Institute, , Icahn School of Medicine at Mount Sinai, ; New York, NY USA
                [23 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Pathology & Immunology, , Washington University School of Medicine, ; St Louis, MO USA
                [24 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, Department of Molecular Microbiology, , Washington University School of Medicine, ; St Louis, MO USA
                [25 ]GRID grid.4367.6, ISNI 0000 0001 2355 7002, The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, , Washington University School of Medicine, ; St Louis, MO USA
                Author information
                http://orcid.org/0000-0003-2258-9031
                http://orcid.org/0000-0002-8266-020X
                http://orcid.org/0000-0003-4914-8228
                http://orcid.org/0000-0003-3260-2631
                http://orcid.org/0000-0002-3097-1129
                http://orcid.org/0000-0001-7331-5511
                http://orcid.org/0000-0001-6652-0701
                http://orcid.org/0000-0002-0866-6961
                http://orcid.org/0000-0003-0890-1922
                http://orcid.org/0000-0003-0404-9947
                http://orcid.org/0000-0002-8743-8579
                http://orcid.org/0000-0003-2441-4729
                http://orcid.org/0000-0001-9321-7839
                http://orcid.org/0000-0002-8960-0728
                http://orcid.org/0000-0003-3583-4497
                http://orcid.org/0000-0001-7787-3051
                http://orcid.org/0000-0002-3287-3987
                http://orcid.org/0000-0002-1376-6916
                http://orcid.org/0000-0002-6416-5096
                http://orcid.org/0000-0002-9380-6569
                http://orcid.org/0000-0002-6557-0771
                http://orcid.org/0000-0001-7768-5157
                http://orcid.org/0000-0001-6988-1975
                http://orcid.org/0000-0003-4213-2354
                http://orcid.org/0000-0002-4397-7132
                http://orcid.org/0000-0003-3133-0849
                http://orcid.org/0000-0002-6551-1827
                http://orcid.org/0000-0003-3156-3132
                http://orcid.org/0000-0002-3820-9542
                http://orcid.org/0000-0002-4700-8224
                http://orcid.org/0000-0002-8791-3165
                http://orcid.org/0000-0001-5061-8296
                Article
                4441
                10.1038/s41586-022-04441-6
                8942849
                35062015
                197c821f-77cf-45c6-a399-4ed3be21d756
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 December 2021
                : 19 January 2022
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                © The Author(s), under exclusive licence to Springer Nature Limited 2022

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                pathogens,sars-cov-2
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                pathogens, sars-cov-2

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