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      Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study

      1 , 2 , 3 , 4 , 1 , 1 , 5 , 6 , 7 , 5 , 8 , 9 , 2 , 3 , 9 , 2 , 3 , 9 , 1 , 10 , 11 , 4 , 1 , 1 , 1 , 1 , 4 , 4 , 5 , 4 , 4 , 12 , 13 , 14 , 15 , 6 , 4 , 10 , 4 , 2 , 3 , 1


      Chinese Medical Journal

      Wolters Kluwer Health

      Bat-origin, Coronavirus, Zoonotic transmission, Pneumonia, Etiology, Next-generation sequencing

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          Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.


          We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital of Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.


          Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.


          A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

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          Most cited references 23

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          Fast and accurate short read alignment with Burrows–Wheeler transform

          Motivation: The enormous amount of short reads generated by the new DNA sequencing technologies call for the development of fast and accurate read alignment programs. A first generation of hash table-based methods has been developed, including MAQ, which is accurate, feature rich and fast enough to align short reads from a single individual. However, MAQ does not support gapped alignment for single-end reads, which makes it unsuitable for alignment of longer reads where indels may occur frequently. The speed of MAQ is also a concern when the alignment is scaled up to the resequencing of hundreds of individuals. Results: We implemented Burrows-Wheeler Alignment tool (BWA), a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps. BWA supports both base space reads, e.g. from Illumina sequencing machines, and color space reads from AB SOLiD machines. Evaluations on both simulated and real data suggest that BWA is ∼10–20× faster than MAQ, while achieving similar accuracy. In addition, BWA outputs alignment in the new standard SAM (Sequence Alignment/Map) format. Variant calling and other downstream analyses after the alignment can be achieved with the open source SAMtools software package. Availability: Contact:
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            Trimmomatic: a flexible trimmer for Illumina sequence data

            Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at Contact: Supplementary information: Supplementary data are available at Bioinformatics online.
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              Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

              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.

                Author and article information

                Chin Med J (Engl)
                Chin. Med. J
                Chinese Medical Journal
                Wolters Kluwer Health
                11 February 2020
                [1 ]National Health Commission of the People's Republic of China Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
                [2 ]Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing 100029, China
                [3 ]Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100029, China
                [4 ]National Health Commission of the People's Republic of China Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
                [5 ]Vision Medicals Co., Ltd, Guangzhou, Guangdong 510000, China
                [6 ]Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei 430079, China
                [7 ]Wuhan Center for Disease Control and Prevention, Wuhan, Hubei 430022, China
                [8 ]Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
                [9 ]Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
                [10 ]Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China
                [11 ]Department of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing, 100084, China
                [12 ]Jin Yin-tan Hospital of Wuhan, Wuhan, Hubei 430022, China
                [13 ]Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei 430030, China
                [14 ]Department of Pulmonary and Critical Care Medicine, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430014, China
                [15 ]Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
                Author notes
                Correspondence to: Dr. Jian-Wei Wang, No. 9 Dong Dan San Tiao, Dongcheng District, Beijing 100730, ChinaE-Mail: ; Dr. Bin Cao, No. 2 East Yinghua Road, Chaoyang District, Beijing, 100029, ChinaE-Mail: caobin_ben@ ; Dr. Qi Jin, No.6 Rong Jing Dong Jie, Daxing District, Beijing 100176, ChinaE-Mail: zdsys@ ; Dr. Chuan Qin, No.5 Pan Jia Yuan Nan Li, Chaoyang District, Beijing 100021, China E-Mail: qinchuan@
                Copyright © 2020 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

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