{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T15:15:38Z","timestamp":1793718938013,"version":"4.6.1"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Education Malaysia","doi-asserted-by":"crossref","award":["FRGS\/1\/2020\/SKK0\/UM\/02\/5"],"award-info":[{"award-number":["FRGS\/1\/2020\/SKK0\/UM\/02\/5"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000774","name":"Defense Threat Reduction Agency","doi-asserted-by":"publisher","award":["HDTRA1-17-1-0027"],"award-info":[{"award-number":["HDTRA1-17-1-0027"]}],"id":[{"id":"10.13039\/100000774","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Severe acute respiratory infections (SARI) pose a great global burden. The contribution of respiratory viruses to adult SARI is relatively understudied in Asia. We aimed to determine viral aetiology of adult SARI patients in Kuala Lumpur, Malaysia.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The prevalence of 20 common (mainly viral) respiratory pathogens, and MERS-CoV, SARS-CoV and 5 bacterial select agents was investigated from May 2017 to October 2019 in 489 SARI adult patients in Kuala Lumpur, Malaysia, using molecular assays (Luminex NxTAG-RPP kit and qPCR assays). Viral metagenomics analysis was performed on 105 negative samples.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Viral respiratory pathogens were detected by PCR in 279 cases (57.1%), including 10 (2.0%) additional detections by metagenomics analysis. The most detected viruses were rhinovirus\/enterovirus (RV\/EV) (49.1%) and influenza virus (7.4%). Three melioidosis cases were detected but no SARS-CoV, MERS-CoV or other bacterial select agents. Bacterial\/viral co-detections and viral co-detections were found in 44 (9.0%) and 27 (5.5%) cases respectively, mostly involving RV\/EV. Independent predictors of critical disease were male gender, chronic lung disease, lack of runny nose and positive blood culture with a significant bacterial pathogen. Asthma and sore throat were associated with increased risk of RV\/EV detection, while among RV\/EV cases, males and those with neurological disease were at increased risk of critical disease.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Prior to the COVID-19 pandemic, the high prevalence of respiratory viruses in adults with SARI was mainly attributed to RV\/EV. Continued surveillance of respiratory virus trends contributes to effective diagnostic, prevention, and treatment strategies.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0273697","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T17:25:02Z","timestamp":1662139502000},"page":"e0273697","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Rhinovirus\/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, Malaysia"],"prefix":"10.1371","volume":"17","author":[{"given":"Yoong Min","family":"Chong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoke Fun","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad Fadhil Hadi","family":"Jamaluddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Statistics on causes of death, Malaysia; 2020 [cited 3 Aug 2022]. https:\/\/www.dosm.gov.my\/v1\/index.php?r=column\/cthemeByCat&cat=401&bul_id=QTU5T0dKQ1g4MHYxd3ZpMzhEMzdRdz09&menu_id=L0pheU43NWJwRWVSZklWdzQ4TlhUUT09\/."},{"key":"pone.0273697.ref003","doi-asserted-by":"crossref","first-page":"953","DOI":"10.2217\/fvl.13.85","article-title":"Addressing the public health burden of respiratory viruses: the Battle against Respiratory Viruses (BRaVe) Initiative","volume":"8","author":"A Legand","year":"2013","journal-title":"Future Virol"},{"key":"pone.0273697.ref004","unstructured":"WHO. Global epidemiological surveillance standards for influenza; 2013 [cited 3 Aug 2022]. https:\/\/www.who.int\/publications\/i\/item\/9789241506601"},{"key":"pone.0273697.ref005","doi-asserted-by":"crossref","first-page":"20285","DOI":"10.2807\/ese.17.39.20285-en","article-title":"Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction","volume":"17","author":"VM Corman","year":"2012","journal-title":"Euro Surveill"},{"key":"pone.0273697.ref006","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1373\/clinchem.2003.023663","article-title":"Detection of SARS coronavirus in patients with severe acute respiratory syndrome by conventional and real-time quantitative reverse transcription-PCR assays","volume":"50","author":"LLM Poon","year":"2004","journal-title":"Clin Chem"},{"key":"pone.0273697.ref007","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1128\/JCM.44.1.85-90.2006","article-title":"Development and evaluation of a real-time PCR assay targeting the type III secretion system of Burkholderia pseudomallei","volume":"44","author":"RT Novak","year":"2006","journal-title":"J Clin Microbiol"},{"key":"pone.0273697.ref008","first-page":"1","article-title":"Highly sensitive real-time PCR for specific detection and quantification of Coxiella burnetii","volume":"6","author":"SR Klee","year":"2006","journal-title":"BMC Microbiol"},{"key":"pone.0273697.ref009","first-page":"009","article-title":"Development of three real-time PCR assays to detect Bacillus anthracis and assessment of diagnostic utility","volume":"S3","author":"TM Parsons","year":"2013","journal-title":"J Bioterr Biodef"},{"key":"pone.0273697.ref010","doi-asserted-by":"crossref","first-page":"5492","DOI":"10.1128\/JCM.41.12.5492-5499.2003","article-title":"Development of a multitarget real-time Taqman PCR assay for enhanced detection of Francisella tularensis in complex specimens","volume":"41","author":"JL Versage","year":"2003","journal-title":"J Clin Microbiol"},{"key":"pone.0273697.ref011","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mcp.2010.09.002","article-title":"Detection of Yersinia pestis using real time PCR in patients with suspected bubonic plague","volume":"25","author":"JM Riehm","year":"2011","journal-title":"Mol Cell Probes"},{"key":"pone.0273697.ref012","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13104-018-3234-8","article-title":"Oxford Screening CSF and Respiratory samples (\u2019OSCAR\u2019): results of a pilot study to screen clinical samples from a diagnostic microbiology laboratory for viruses using Illumina next generation sequencing","volume":"11","author":"C Sharp","year":"2018","journal-title":"BMC Res Notes"},{"key":"pone.0273697.ref013","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.virol.2017.06.019","article-title":"Use of Sequence-Independent, Single-Primer-Amplification (SISPA) for rapid detection, identification, and characterization of avian RNA viruses","volume":"509","author":"K Chrzastek","year":"2017","journal-title":"Virology"},{"key":"pone.0273697.ref014","doi-asserted-by":"crossref","first-page":"giaa111","DOI":"10.1093\/gigascience\/giaa111","article-title":"IDseq\u2014An open source cloud-based pipeline and analysis service for metagenomic pathogen detection and monitoring","volume":"9","author":"KL Kalantar","year":"2020","journal-title":"GigaScience"},{"key":"pone.0273697.ref015","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1101\/gr.238170.118","article-title":"Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid","volume":"29","author":"S Miller","year":"2019","journal-title":"Genome Res"},{"key":"pone.0273697.ref016","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12915-014-0087-z","article-title":"Reagent and laboratory contamination can critically impact sequence-based microbiome analyses","volume":"12","author":"SJ Salter","year":"2014","journal-title":"BMC Biol"},{"key":"pone.0273697.ref017","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4269\/ajtmh.15-0799","article-title":"Enteroviruses and rhinoviruses: molecular epidemiology of the most influenza-like illness associated viruses in Senegal","volume":"95","author":"A Fall","year":"2016","journal-title":"Am J Trop Med Hyg"},{"key":"pone.0273697.ref018","doi-asserted-by":"crossref","first-page":"2698","DOI":"10.1128\/JCM.00542-06","article-title":"Sensitive, seminested PCR amplification of VP1 sequences for direct identification of all enterovirus serotypes from original clinical specimens","volume":"44","author":"WA Nix","year":"2006","journal-title":"J Clin Microbiol"},{"key":"pone.0273697.ref019","unstructured":"Rambaut A. FigTree v1.4.2, a graphical viewer of phylogenetic trees; 2020 [cited 3 Aug 2022]. http:\/\/tree.bio.ed.ac.uk\/software\/figtree\/."},{"key":"pone.0273697.ref020","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1471-2431-12-32","article-title":"Epidemiology and seasonality of respiratory viral infections in hospitalized children in Kuala Lumpur, Malaysia: a retrospective study of 27 years","volume":"12","author":"CS Khor","year":"2012","journal-title":"BMC Pediatr"},{"key":"pone.0273697.ref021","doi-asserted-by":"crossref","first-page":"ofz074","DOI":"10.1093\/ofid\/ofz074","article-title":"High prevalence of viral infections among hospitalized pneumonia patients in equatorial Sarawak, Malaysia","volume":"6","author":"T-H Toh","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"pone.0273697.ref022","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1111\/jpc.14076","article-title":"Respiratory virus detection and co-infection in children and adults in 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severe acute respiratory tract infection in Shanghai, 2013\u20132015","volume":"9","author":"Y Zhao","year":"2018","journal-title":"Front Microbiol"},{"key":"pone.0273697.ref026","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.3389\/fmicb.2019.02737","article-title":"The emerging role of rhinoviruses in lower respiratory tract infections in children\u2013clinical and molecular epidemiological study from Croatia, 2017\u20132019","volume":"10","author":"S Ljubin-Sternak","year":"2019","journal-title":"Front Microbiol"},{"key":"pone.0273697.ref027","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/jmv.25313","article-title":"Seasonal influenza activity based on laboratory surveillance in Malaysia, 2011\u20132016","volume":"91","author":"I-C Sam","year":"2018","journal-title":"J Med Virol"},{"key":"pone.0273697.ref028","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1186\/s12879-021-06360-9","article-title":"Influenza in Malaysian adult patients hospitalized with community-acquired pneumonia, acute exacerbation of chronic obstructive pulmonary disease or asthma: a multicenter, active surveillance study","volume":"21","author":"YK Pang","year":"2021","journal-title":"BMC Infect Dis"},{"key":"pone.0273697.ref029","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1016\/j.jinf.2020.04.032","article-title":"Comparative seasonalities of influenza A, B and \u2019common cold\u2019 coronaviruses\u2014setting the scene for SARS-CoV-2 infections and possible unexpected host immune interactions","volume":"81","author":"Y Liu","year":"2020","journal-title":"J Infect"},{"key":"pone.0273697.ref030","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.4269\/ajtmh.14-0354","article-title":"Short report: Predictors of severe disease in melioidosis patients in Kuala Lumpur, Malaysia","volume":"91","author":"AD Mohd Roslani","year":"2014","journal-title":"Am J Trop Med 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Microbiol"},{"key":"pone.0273697.ref034","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jcv.2015.03.013","article-title":"Prospective evaluation of rhinovirus infection in healthy young children","volume":"66","author":"N Principi","year":"2015","journal-title":"J Clin Virol"},{"key":"pone.0273697.ref035","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/infdis\/jiv323","article-title":"Respiratory viral detection in children and adults: comparing asymptomatic controls and patients with community-acquired pneumonia","volume":"213","author":"WH Self","year":"2016","journal-title":"J Infect Dis"},{"key":"pone.0273697.ref036","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.1128\/JCM.02094-10","article-title":"Frequent detection of respiratory viruses without symptoms: toward defining clinically relevant cutoff values","volume":"49","author":"RR Jansen","year":"2011","journal-title":"J Clin 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