{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:10:08Z","timestamp":1792894208828,"version":"4.5.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Within 36\u2009h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients\u2019 respiratory symptoms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/clinchem\/hvaa106","type":"journal-article","created":{"date-parts":[[2020,5,4]],"date-time":"2020-05-04T19:12:23Z","timestamp":1588619543000},"page":"966-972","source":"Crossref","is-referenced-by-count":72,"title":["Metagenomic Analysis Reveals Clinical SARS-CoV-2 Infection and Bacterial or Viral Superinfection and Colonization"],"prefix":"10.1093","volume":"66","author":[{"given":"Vikas","family":"Peddu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan C","family":"Shean","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasata","family":"Shrestha","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garrett A","family":"Perchetti","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S","family":"Minot","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavitra","family":"Roychoudhury","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meei-Li","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Nalla","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shriya B","family":"Reddy","sequence":"first","affiliation":[{"name":"Department of Medicine, Boston University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quynh","family":"Phung","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Reinhardt","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R","family":"Jerome","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-0527","authenticated-orcid":false,"given":"Alexander L","family":"Greninger","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, WA"},{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"2020070608442761100_hvaa106-B1","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1056\/NEJMoa2001191","article-title":"First case of 2019 Novel Coronavirus in the United States","volume":"382","author":"Holshue","year":"2020","journal-title":"N Engl J Med"},{"key":"2020070608442761100_hvaa106-B2","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","author":"Dong","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"2020070608442761100_hvaa106-B3","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"2020070608442761100_hvaa106-B4","author":"Chen","year":"2020"},{"key":"2020070608442761100_hvaa106-B5","author":"Yang","year":"2020"},{"key":"2020070608442761100_hvaa106-B6","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0140-6736(20)30211-7","article-title":"Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study","volume":"395","author":"Chen","year":"2020","journal-title":"Lancet"},{"key":"2020070608442761100_hvaa106-B7","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan","volume":"395","author":"Huang","year":"2020","journal-title":"China. Lancet"},{"key":"2020070608442761100_hvaa106-B8","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.jinf.2017.10.012","article-title":"Metagenomic analysis identified co-infection with human rhinovirus C and bocavirus 1 in an adult suffering from severe pneumonia","volume":"76","author":"Li","year":"2018","journal-title":"J Infect"},{"key":"2020070608442761100_hvaa106-B9","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1128\/JCM.00216-06","article-title":"Comparison of real-time PCR assays with fluorescent-antibody assays for diagnosis of respiratory virus infections in children","volume":"44","author":"Kuypers","year":"2006","journal-title":"J Clin Microbiol"},{"key":"2020070608442761100_hvaa106-B10","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1128\/JCM.01881-16","article-title":"Rapid metagenomic next-generation sequencing during an investigation of hospital-acquired human parainfluenza virus 3 infections","volume":"55","author":"Greninger","year":"2017","journal-title":"J Clin Microbiol"},{"key":"2020070608442761100_hvaa106-B11","year":"2020"},{"key":"2020070608442761100_hvaa106-B12","author":"Breitwieser","year":"2019"},{"key":"2020070608442761100_hvaa106-B13","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"2020070608442761100_hvaa106-B14","year":"2020"},{"key":"2020070608442761100_hvaa106-B15","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods"},{"key":"2020070608442761100_hvaa106-B16","author":"Zaharia"},{"key":"2020070608442761100_hvaa106-B17","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2020070608442761100_hvaa106-B18","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1101\/gr.213959.116","article-title":"metaSPAdes: a new versatile metagenomic assembler","volume":"27","author":"Nurk","year":"2017","journal-title":"Genome Res"},{"key":"2020070608442761100_hvaa106-B19","year":"2020"},{"key":"2020070608442761100_hvaa106-B20","doi-asserted-by":"crossref","first-page":"e13381","DOI":"10.1371\/journal.pone.0013381","article-title":"A metagenomic analysis of pandemic influenza A (2009 H1N1) infection in patients from North America","volume":"5","author":"Greninger","year":"2010","journal-title":"PLoS One"},{"key":"2020070608442761100_hvaa106-B21","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1128\/CMR.15.1.125-144.2002","article-title":"Moraxella catarrhalis: from emerging to established pathogen","volume":"15","author":"Verduin","year":"2002","journal-title":"Clinc Microbiol Rev"},{"key":"2020070608442761100_hvaa106-B22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1513\/pats.201006-038RN","article-title":"Microbiology of sinusitis","volume":"8","author":"Brook","year":"2011","journal-title":"Proc Am Thorac Soc"},{"key":"2020070608442761100_hvaa106-B23","first-page":"26","author":"Wu","year":"2020"}],"container-title":["Clinical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/clinchem\/advance-article-pdf\/doi\/10.1093\/clinchem\/hvaa106\/33383926\/hvaa106.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/66\/7\/966\/33466940\/hvaa106.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/clinchem\/article-pdf\/66\/7\/966\/33466940\/hvaa106.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T12:44:52Z","timestamp":1594039492000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/clinchem\/article\/66\/7\/966\/5831830"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,12]]},"references-count":23,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,6,12]]},"published-print":{"date-parts":[[2020,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/clinchem\/hvaa106","relation":{},"ISSN":["0009-9147","1530-8561"],"issn-type":[{"value":"0009-9147","type":"print"},{"value":"1530-8561","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7]]},"published":{"date-parts":[[2020,6,12]]}}}