scispace - formally typeset
Search or ask a question
Journal ArticleDOI

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

TL;DR: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans and the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
Abstract: Background: 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. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, 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. Results: 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 99.8–99.9% 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 87.6–87.7% 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. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans. Key words: Bat-origin; Coronavirus; Zoonotic transmission; Pneumonia; Etiology; Next-generation sequencing
Citations
More filters
Journal ArticleDOI
TL;DR: Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough, and bilateral lung involvement with ground-glass opacity was themost common finding from computed tomography images of the chest.

4,318 citations


Cites background from "Identification of a novel coronavir..."

  • ...1 ), but it is more distant from SARS-CoV (~79% similarity) and Middle East respiratory syndrome coronavirus (MERS-CoV) (~50% similarity) [23 , 25 , 26] ....

    [...]

Journal ArticleDOI
TL;DR: The symptoms, epidemiology, transmission, pathogenesis, phylogenetic analysis and future directions to control the spread of this fatal disease are highlighted.

4,065 citations

Journal ArticleDOI
TL;DR: It is shown that the SARS-CoV-2 spike protein is less stable than that of SARS -CoV, and limited cross-neutralization activities between SARS and COVID-19 patients’ sera showlimited cross- neutralization activities, suggesting that recovery from one infection might not protect against the other.
Abstract: Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.

2,622 citations

Journal ArticleDOI
TL;DR: The results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by natural selection besides recombination.
Abstract: The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses had two major lineages (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. We found that L lineage was more prevalent than the S lineage within the limited patient samples we examined. The implication of these evolutionary changes on disease etiology remains unclear. These findings strongly underscores the urgent need for further comprehensive studies that combine viral genomic data, with epidemiological studies of coronavirus disease 2019 (COVID-19).

1,369 citations


Cites background from "Identification of a novel coronavir..."

  • ...9%, suggesting a very recent host shift into humans [1-3]....

    [...]

Journal ArticleDOI
TL;DR: The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases, and the detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset.
Abstract: Background The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)-based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. Methods The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. Results The median duration of IgM and IgA antibody detection was 5 (IQR, 3-6) days, while IgG was detected 14 (IQR, 10-18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). Conclusions The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases.

1,350 citations


Cites background or methods from "Identification of a novel coronavir..."

  • ...A novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease in 2019 (COVID-19) emerged as a major pandemic [1, 2]....

    [...]

  • ...Among them, 43 (20 severe and 23 mild to moderate) were confirmed virus positive (referred as “confirmed cases” [CCs]) by deep sequencing or a qPCR assay with a detection limit of 1 copy/μL, as previously reported [1, 2], while 58 cases (5 severe and 53 mild to moderate) suspected to be infected with SARS-CoV-2 based on clinical manifestation, chest radiography imaging, and epidemiology but no virus were detected by deep sequencing or a qPCR assay (referred as “probable cases” [PCs])....

    [...]

References
More filters
Journal ArticleDOI
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, 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.
Abstract: 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: http://maq.sourceforge.net Contact: [email protected]

43,862 citations

Journal ArticleDOI
TL;DR: Timmomatic is developed as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data and 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.
Abstract: 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 http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: ed.nehcaa-htwr.1oib@ledasu Supplementary information: Supplementary data are available at Bioinformatics online.

39,291 citations

Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

4,809 citations


"Identification of a novel coronavir..." refers background in this paper

  • ...Sequence homology analysis of the viral genome showed that the CoV identified in this study is distinct from any of the known human CoVs, including SARS-CoV and MERS-CoV....

    [...]

  • ...Since the beginning of this century, two zoonotic CoVs, SARSCoV and MERS-CoV, have been identified to cause severe human diseases.([3,4,7]) The outbreak of SARS-CoV in 2003 was responsible for 8096 cases and 774 deaths worldwide....

    [...]

  • ...The phylogenetic trees constructed with the sequences of the RdRp, S, and N genes, and the whole genome using a maximum-likelihood model showed that all five novel CoVs were closely related to bat SL-CoVs ZXC21 and ZC45, but in a separate evolutionary lineage under the 1 ORF3 and intact ORF8 gene regions were present in the novel CoVs, which are the characteristic features of batorigin CoVs....

    [...]

  • ...[5,6] Since the beginning of this century, two zoonotic CoVs, SARSCoV and MERS-CoV, have been identified to cause severe human diseases....

    [...]

  • ...Clarification of the coronavirome in animals, particularly in bats as a key reservoir of a wide range of CoVs, should be a priority for any task force....

    [...]

Journal ArticleDOI
TL;DR: The viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome are explored and the diversity and potential of bat-borne coronaviruses are highlighted.
Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs. Coronaviruses have a broad host range and distribution, and some highly pathogenic lineages have spilled over to humans and animals. Here, Cui, Li and Shi explore the viral factors that enabled the emergence of diseases such as severe acute respiratory syndrome and Middle East respiratory syndrome.

3,970 citations

Journal ArticleDOI
TL;DR: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronav virus into the human population in the twenty-first century, and the current state of development of measures to combat emerging coronaviruses is discussed.
Abstract: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 marked the second introduction of a highly pathogenic coronavirus into the human population in the twenty-first century. The continuing introductions of MERS-CoV from dromedary camels, the subsequent travel-related viral spread, the unprecedented nosocomial outbreaks and the high case-fatality rates highlight the need for prophylactic and therapeutic measures. Scientific advancements since the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) pandemic allowed for rapid progress in our understanding of the epidemiology and pathogenesis of MERS-CoV and the development of therapeutics. In this Review, we detail our present understanding of the transmission and pathogenesis of SARS-CoV and MERS-CoV, and discuss the current state of development of measures to combat emerging coronaviruses.

2,794 citations


"Identification of a novel coronavir..." refers background in this paper

  • ...Since the beginning of this century, two zoonotic CoVs, SARSCoV and MERS-CoV, have been identified to cause severe human diseases.([3,4,7]) The outbreak of SARS-CoV in 2003 was responsible for 8096 cases and 794 deaths worldwide....

    [...]

Related Papers (5)