{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:28:41Z","timestamp":1790692121668,"version":"4.1.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32041004"],"award-info":[{"award-number":["32041004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31930001"],"award-info":[{"award-number":["31930001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32130002"],"award-info":[{"award-number":["32130002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81861138003"],"award-info":[{"award-number":["81861138003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81672057"],"award-info":[{"award-number":["81672057"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARC Australian Laureate Fellowship","award":["FL170100022"],"award-info":[{"award-number":["FL170100022"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    At the end of 2019 Wuhan witnessed an outbreak of \u201catypical pneumonia\u201d that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus denoted SARS-CoV-2. To provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their \u201ctotal infectome\u201d, including viruses, bacteria and fungi. We identified 35 pathogen species, comprising 13 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (13.5%). SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen\u2013\n                    <jats:italic>Chlamydia psittaci<\/jats:italic>\n                    . Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016\u20132017.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010259","type":"journal-article","created":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T13:26:04Z","timestamp":1645104364000},"page":"e1010259","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":35,"title":["Total infectome characterization of respiratory infections in pre-COVID-19 Wuhan, China"],"prefix":"10.1371","volume":"18","author":[{"given":"Mang","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Hua","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Ling","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Gang","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-3552","authenticated-orcid":true,"given":"Edward C.","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-3691","authenticated-orcid":true,"given":"Yong-Zhen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,17]]},"reference":[{"key":"ppat.1010259.ref001","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41586-020-2008-3","article-title":"A new coronavirus associated with human respiratory disease in China","volume":"579","author":"F Wu","year":"2020","journal-title":"Nature"},{"key":"ppat.1010259.ref002","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"P Zhou","year":"2020","journal-title":"Nature"},{"key":"ppat.1010259.ref003","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1056\/NEJMoa2001316","article-title":"Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia","volume":"382","author":"Q Li","year":"2020","journal-title":"N Engl J Med"},{"key":"ppat.1010259.ref004","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev-virology-092818-015851","article-title":"Expanding the RNA virosphere by unbiased metagenomics","volume":"6","author":"YZ Zhang","year":"2019","journal-title":"Annu Rev Virol"},{"key":"ppat.1010259.ref005","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.3201\/eid2307.161863","article-title":"Francisella tularensis ssp. holarctica in Ringtail Possums, Australia","volume":"23","author":"JS Eden","year":"2017","journal-title":"Emerg Infect 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metagenomic next-generation sequencing in children with severe nonresponding pneumonia.","volume":"15","author":"H Wang","year":"2020","journal-title":"PLoS One"},{"key":"ppat.1010259.ref010","doi-asserted-by":"crossref","first-page":"S416","DOI":"10.1093\/cid\/ciaa1516","article-title":"Clinical utility of in-house metagenomic next-generation sequencing for the diagnosis of lower respiratory tract infections and analysis of the host immune response","volume":"71","author":"H Chen","year":"2020","journal-title":"Clin Infect Dis"},{"key":"ppat.1010259.ref011","doi-asserted-by":"crossref","first-page":"960","DOI":"10.3390\/v12090960","article-title":"The Virome of Acute Respiratory Diseases in Individuals at Risk of Zoonotic Infections.","volume":"12","author":"N Thi Kha Tu","year":"2020","journal-title":"Viruses"},{"key":"ppat.1010259.ref012","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected 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