{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:36:40Z","timestamp":1787333800020,"version":"build-2736575974"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2025-I2M-FGS-007"],"award-info":[{"award-number":["2025-I2M-FGS-007"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.8257012927"],"award-info":[{"award-number":["No.8257012927"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project of the Ministry of Science and Technology of China","doi-asserted-by":"crossref","award":["No.2024ZD0522501"],"award-info":[{"award-number":["No.2024ZD0522501"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["No.2023ZD0506200\/2023ZD0506203"],"award-info":[{"award-number":["No.2023ZD0506200\/2023ZD0506203"]}]}],"content-domain":{"domain":["www.plosdigitalhealth.org"],"crossmark-restriction":false},"short-container-title":["PLOS Digit Health"],"abstract":"<jats:p>Clinical symptoms are critical for diagnosing and managing upper respiratory tract infections, yet systematic comparisons across common pathogens remain limited. We aimed to characterize symptom signatures across common respiratory pathogens and to develop approaches that support the prioritization of diagnostic testing across pathogens. Using a large-scale, home-based multiplex PCR testing dataset, we characterized symptom profiles across common respiratory pathogens stratified by age and sex. Hierarchical clustering was applied to group pathogens into symptom-based categories, and a multilayer perceptron (MLP) model was trained to predict these cluster-level categories. A post-hoc refinement combined MLP outputs with contemporaneous epidemiological data to further prioritize likely pathogens within predicted categories. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), classification accuracy, and related metrics. Symptom profiles overlapped substantially across pathogens, with differences being more categorical than pathogen-specific: RSV, HCoV, HPIV, and HRV were predominantly characterized by respiratory symptoms, whereas influenza A\/B and SARS-CoV-2 showed more pronounced systemic manifestations. The MLP model achieved high AUCs (0.80\u20130.92, depending on age group) with specificities exceeding 75% but lower sensitivities, reflecting a conservative prediction pattern. Integrating cluster-level predictions with contemporaneous epidemiology improved the prioritization of prevalent pathogens, though performance remained limited for less common ones. When expanding predictions to the top three likely pathogens, the model enabled diagnostic test prioritization with an overall accuracy of 0.83 (95% CI, 0.82\u20130.84). Our study supports the use of readily available symptom data to inform the prioritization of diagnostic testing, particularly during outbreaks or in resource-limited settings where timely laboratory testing is constrained. In addition, the systematic symptom signatures identified across common respiratory pathogens may inform the development and optimization of symptom-based patient-reported outcomes for future antiviral trials.<\/jats:p>","DOI":"10.1371\/journal.pdig.0001656","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:22:31Z","timestamp":1787332951000},"page":"e0001656","update-policy":"https:\/\/doi.org\/10.1371\/journal.pdig.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distinguishing common respiratory pathogens using machine learning of symptom profiles to prioritize diagnostic testing"],"prefix":"10.1371","volume":"5","author":[{"given":"Chunyan","family":"Xiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6991-0350","authenticated-orcid":true,"given":"Bin","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"issue":"1","key":"pdig.0001656.ref001","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/S1473-3099(24)00430-4","article-title":"Global, regional, and national burden of upper respiratory infections and otitis media, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021","volume":"25","year":"2025","journal-title":"Lancet Infect Dis"},{"key":"pdig.0001656.ref002","doi-asserted-by":"crossref","first-page":"100986","DOI":"10.1016\/j.eclinm.2021.100986","article-title":"Global burden of upper respiratory infections in 204 countries and territories, from 1990 to 2019","volume":"37","author":"X Jin","year":"2021","journal-title":"EClinicalMedicine"},{"key":"pdig.0001656.ref003","volume-title":"WHO guidelines approved by the guidelines review committee","year":"2024"},{"key":"pdig.0001656.ref004","unstructured":"WHO. COVID-19 Target product profiles for priority diagnostics to support response to the COVID-19 pandemic v.1.0. 2020. Available from: https:\/\/www.who.int\/publications\/m\/item\/covid-19-target-product-profiles-for-priority-diagnostics-to-support-response-to-the-covid-19-pandemic-v.0.1"},{"key":"pdig.0001656.ref005","unstructured":"WHO. Influenza (seasonal). 2025. Available from: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/influenza-(seasonal)"},{"issue":"7","key":"pdig.0001656.ref006","doi-asserted-by":"crossref","first-page":"500","DOI":"10.7326\/0003-4819-156-7-201204030-00403","article-title":"Accuracy of rapid influenza diagnostic tests: a meta-analysis","volume":"156","author":"C Chartrand","year":"2012","journal-title":"Ann Intern Med"},{"issue":"1","key":"pdig.0001656.ref007","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12916-024-03351-w","article-title":"SARS-CoV-2, influenza A\/B and respiratory syncytial virus positivity and association with influenza-like illness and self-reported symptoms, over the 2022\/23 winter season in the UK: a longitudinal surveillance cohort","volume":"22","author":"E Dietz","year":"2024","journal-title":"BMC Med"},{"issue":"1","key":"pdig.0001656.ref008","doi-asserted-by":"crossref","first-page":"12511","DOI":"10.1038\/s41598-023-38869-1","article-title":"Symptom profiles of community cases infected by influenza, RSV, rhinovirus, seasonal coronavirus, and SARS-CoV-2 variants of concern","volume":"13","author":"C Geismar","year":"2023","journal-title":"Sci Rep"},{"issue":"1","key":"pdig.0001656.ref009","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41533-025-00414-0","article-title":"Differences in clinical characteristics between coronavirus disease 2019 (COVID-19) and influenza: a systematic review and meta-analysis","volume":"35","author":"Y Han","year":"2025","journal-title":"NPJ Prim Care Respir Med"},{"key":"pdig.0001656.ref010","unstructured":"CDCC. National COVID-19 Epidemic Situation in China. 2025. Available from: https:\/\/www.chinacdc.cn\/jksj\/xgbdyq\/202501\/t20250107_303736.html"},{"key":"pdig.0001656.ref011","unstructured":"FDA. Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. 2009. Available from: https:\/\/www.fda.gov\/media\/77832\/download"},{"issue":"8","key":"pdig.0001656.ref012","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1001\/jama.283.8.1016","article-title":"Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group","volume":"283","author":"JJ Treanor","year":"2000","journal-title":"JAMA"},{"issue":"10","key":"pdig.0001656.ref013","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1056\/NEJMoa1716197","article-title":"Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents","volume":"379","author":"FG Hayden","year":"2018","journal-title":"N Engl J Med"},{"issue":"2","key":"pdig.0001656.ref014","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/cid\/ciae551","article-title":"Alleviation of COVID-19 Symptoms and Reduction in Healthcare Utilization Among High-risk Patients Treated With Nirmatrelvir\/Ritonavir (NMV\/R): A Phase 3 Randomized Trial","volume":"80","author":"J Hammond","year":"2025","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pdig.0001656.ref015","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jval.2017.04.014","article-title":"Reliability, Validity, and Responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO\u00a9) Scores in Influenza-Positive Patients","volume":"21","author":"JH Powers","year":"2018","journal-title":"Value Health"},{"issue":"3","key":"pdig.0001656.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0194180","article-title":"Performance of the inFLUenza Patient-Reported Outcome (FLU-PRO) diary in patients with influenza-like illness (ILI)","volume":"13","author":"JH Powers","year":"2018","journal-title":"PLoS One"},{"issue":"1","key":"pdig.0001656.ref017","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s41687-023-00593-9","article-title":"Evaluation of symptoms in respiratory syncytial virus infection in adults: psychometric evaluation of the Respiratory Infection Intensity and Impact Questionnaire\u2122 symptom scores","volume":"7","author":"RH Osborne","year":"2023","journal-title":"J Patient Rep Outcomes"},{"issue":"4","key":"pdig.0001656.ref018","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2022-067878","article-title":"Diagnostic models predicting paediatric viral acute respiratory infections: a systematic review","volume":"13","author":"DA Rankin","year":"2023","journal-title":"BMJ Open"},{"key":"pdig.0001656.ref019","doi-asserted-by":"crossref","first-page":"595","DOI":"10.2147\/RMHP.S291498","article-title":"Machine Learning-Based Decision Model to Distinguish Between COVID-19 and Influenza: A Retrospective, Two-Centered, Diagnostic Study","volume":"14","author":"X Zhou","year":"2021","journal-title":"Risk Manag Healthc Policy"},{"issue":"1","key":"pdig.0001656.ref020","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41746-021-00467-8","article-title":"A vital sign-based prediction algorithm for differentiating COVID-19 versus seasonal influenza in hospitalized patients","volume":"4","author":"N Yanamala","year":"2021","journal-title":"NPJ Digit Med"},{"issue":"2","key":"pdig.0001656.ref021","doi-asserted-by":"crossref","first-page":"539","DOI":"10.7150\/ijbs.53982","article-title":"A rapid screening classifier for diagnosing COVID-19","volume":"17","author":"Y Xia","year":"2021","journal-title":"Int J Biol Sci"},{"issue":"1","key":"pdig.0001656.ref022","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13040-022-00288-9","article-title":"Influenza, dengue and common cold detection using LSTM with fully connected neural network and keywords selection","volume":"15","author":"W Nadda","year":"2022","journal-title":"BioData Min"},{"key":"pdig.0001656.ref023","unstructured":"Upsurge of respiratory illnesses among children-Northern China. 2023. Available from: https:\/\/www.who.int\/emergencies\/disease-outbreak-news\/item\/2023-DON494#:~:text=Since%20mid-October%202023%2C%20the%20World%20Health%20Organization%20%28WHO%29,in%20respiratory%20illness%20in%20children%20in%20northern%20China"},{"key":"pdig.0001656.ref024","unstructured":"CDC. Weekly Influenza Surveillance Report; National Sentinel Surveillance of Acute Respiratory Infectious Diseases; etc. 2025. Available from: https:\/\/www.chinacdc.cn\/jksj\/jksj04_14249\/"}],"container-title":["PLOS Digital Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pdig.0001656","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T17:22:37Z","timestamp":1787332957000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pdig.0001656"}},"subtitle":[],"editor":[{"given":"Cleva","family":"Villanueva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":24,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pdig.0001656","relation":{},"ISSN":["2767-3170"],"issn-type":[{"value":"2767-3170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}