{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:07:10Z","timestamp":1785899230407,"version":"3.56.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Rhinoviruses (RVs) are a well-known trigger of wheezing episodes in children with asthma. Their role in other pediatric chronic medical conditions is not fully known.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients \u226421 years hospitalized or evaluated as outpatients with symptomatic RV infection were identified from 2011\u20132013. Patients were categorized based on the type of underlying disease and differences in clinical parameters, RV loads (C\n                      <jats:sub>T<\/jats:sub>\n                      values), viral, bacterial and fungal co-infections and clinical outcomes were compared between groups. Multivariable analyses were performed to identify the comorbidities associated with oxygen requirement, PICU admission, and prolonged hospitalization.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 1,899 children identified, 77.7% (n\u2009=\u20091477) had an underlying comorbidity including asthma\/atopy (36.8%), prematurity (7.7%), chronic respiratory diseases (6.4%), congenital heart disease (CHD, 3.2%), immunocompromised hosts (ICH; 1.4%) and others (22.2%). Prevalence of comorbidities increased with age (70%, infants\n                      <jats:italic>vs<\/jats:italic>\n                      84%-87%, children &gt;1 year; p\u2009&lt;\u20090.0001). Median RV loads were intermediate-high (24\u201326 C\n                      <jats:sub>T<\/jats:sub>\n                      values), irrespective of the underlying disease. RV\/viral co-detections were identified in 11% of ICH vs 20%- 30% in all other children whereas bacterial co-infections were identified in 2.9% of children. Multivariable models identified asthma\/atopy, prematurity, CHD and bacterial co-infections consistently associated with all three clinical outcomes (p\u2009&lt;\u20090.0001). Older age and higher RV loads were also associated with increased odds of PICU admission.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The prevalence of comorbidities was high in children with RV infections. Of those, asthma\/atopy, prematurity and CHD were consistently associated with severe disease. Higher RV loads and bacterial co-infections, although infrequent, were also associated with worse clinical outcomes, suggesting the importance of defining clinical phenotypes for future targeted interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0313237","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T14:02:14Z","timestamp":1747231334000},"page":"e0313237","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["The differential burden of acute rhinovirus infections in children with underlying conditions"],"prefix":"10.1371","volume":"20","author":[{"given":"Mar\u00eda Isabel","family":"S\u00e1nchez C\u00f3dez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Benavente Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Moyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Leber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavio","family":"Ramilo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5983-8006","authenticated-orcid":true,"given":"Asuncion","family":"Mejias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"issue":"15","key":"pone.0313237.ref001","doi-asserted-by":"crossref","first-page":"7418","DOI":"10.1128\/JVI.02290-09","article-title":"The ABCs of rhinoviruses, wheezing, and asthma","volume":"84","author":"JE Gern","year":"2010","journal-title":"J Virol"},{"key":"pone.0313237.ref002","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jcv.2014.11.006","article-title":"Molecular epidemiology of human rhinovirus infections in the pediatric emergency department","volume":"62","author":"EK Martin","year":"2015","journal-title":"J Clin Virol"},{"key":"pone.0313237.ref003","article-title":"Rhinovirus - not just the common cold","author":"SB Drysdale","year":"2017","journal-title":"J Infect"},{"issue":"8","key":"pone.0313237.ref004","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1093\/cid\/civ486","article-title":"Community surveillance of respiratory viruses among families in the utah better identification of germs-longitudinal viral epidemiology (BIG-LoVE) study","volume":"61","author":"CL Byington","year":"2015","journal-title":"Clin Infect Dis"},{"issue":"7","key":"pone.0313237.ref005","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1002\/jmv.21790","article-title":"Viral respiratory infections in hospitalized and community control children in Alaska","volume":"82","author":"RJ Singleton","year":"2010","journal-title":"J Med Virol"},{"issue":"1","key":"pone.0313237.ref006","doi-asserted-by":"crossref","DOI":"10.1128\/JCM.00716-18","article-title":"PCR detection of respiratory pathogens in asymptomatic and symptomatic adults","volume":"57","author":"N Sundell","year":"2019","journal-title":"J Clin Microbiol"},{"issue":"3","key":"pone.0313237.ref007","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.jaip.2022.01.006","article-title":"Rhinovirus infections and their roles in asthma: etiology and exacerbations","volume":"10","author":"DJ Jackson","year":"2022","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"2","key":"pone.0313237.ref008","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2013-2216","article-title":"Human rhinovirus and disease severity in children","volume":"133","author":"LF Costa","year":"2014","journal-title":"Pediatrics"},{"issue":"3","key":"pone.0313237.ref009","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/ppul.26267","article-title":"Impact of viral respiratory infections on pulmonary exacerbations in children with cystic fibrosis","volume":"58","author":"N Gonzalez-Rosales","year":"2023","journal-title":"Pediatr Pulmonol"},{"issue":"3","key":"pone.0313237.ref010","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/cid\/ciae216","article-title":"The impact of pretransplant respiratory virus detection on posttransplant outcomes in children undergoing hematopoietic cell transplantation","volume":"79","author":"SR Kim","year":"2024","journal-title":"Clin Infect Dis"},{"issue":"7","key":"pone.0313237.ref011","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/INF.0000000000000718","article-title":"Clinical and virological characteristics of early and moderate preterm infants readmitted with viral respiratory infections","volume":"34","author":"ML Garc\u00eda-Garcia","year":"2015","journal-title":"Pediatr Infect Dis J"},{"issue":"3","key":"pone.0313237.ref012","article-title":"Age limit of pediatrics","volume":"140","author":"Committee On Practice And Ambulatory Medicine","year":"2017","journal-title":"Pediatrics"},{"issue":"2","key":"pone.0313237.ref013","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3390\/v13020295","article-title":"Viral loads and disease severity in children with rhinovirus-associated illnesses","volume":"13","author":"MI Sanchez-Codez","year":"2021","journal-title":"Viruses"},{"issue":"2","key":"pone.0313237.ref014","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1128\/JCM.01739-07","article-title":"Real-time reverse transcription-PCR assay for comprehensive detection of human rhinoviruses","volume":"46","author":"X Lu","year":"2008","journal-title":"J Clin Microbiol"},{"issue":"9","key":"pone.0313237.ref015","doi-asserted-by":"crossref","DOI":"10.1002\/jmv.29833","article-title":"The interdependence between rhinovirus cycle threshold values, viral co-detections, and clinical disease severity in children with and without comorbidities","volume":"96","author":"MI S\u00e1nchez C\u00f3dez","year":"2024","journal-title":"J Med Virol"},{"issue":"11","key":"pone.0313237.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0167111","article-title":"Enterovirus D68 in hospitalized children: sequence variation, viral loads and clinical outcomes","volume":"11","author":"K Moyer","year":"2016","journal-title":"PLoS One"},{"issue":"5","key":"pone.0313237.ref017","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.bbmt.2018.12.005","article-title":"Human rhinovirus infections in hematopoietic cell transplant recipients: risk score for progression to lower respiratory tract infection","volume":"25","author":"A Waghmare","year":"2019","journal-title":"Biol Blood Marrow Transplant"},{"issue":"4","key":"pone.0313237.ref018","doi-asserted-by":"crossref","first-page":"230","DOI":"10.4103\/atm.ATM_291_17","article-title":"Clinical characteristics and outcomes of human rhinovirus positivity in hospitalized children","volume":"13","author":"P-Y Iroh Tam","year":"2018","journal-title":"Ann Thorac Med"},{"issue":"11","key":"pone.0313237.ref019","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1093\/infdis\/jir634","article-title":"Human rhinovirus species associated with hospitalizations for acute respiratory illness in young US children","volume":"204","author":"MK Iwane","year":"2011","journal-title":"J Infect Dis"},{"issue":"1","key":"pone.0313237.ref020","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s12879-023-08084-4","article-title":"Clinical characteristics and outcomes of children with single or co-detected rhinovirus-associated acute respiratory infection in Middle Tennessee","volume":"23","author":"JZ Amarin","year":"2023","journal-title":"BMC Infect Dis"},{"key":"pone.0313237.ref021","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.jcv.2015.10.024","article-title":"Clinical, virological and epidemiological characteristics of rhinovirus infections in early childhood: a comparison between non-hospitalised and hospitalised children","volume":"73","author":"AHL Bruning","year":"2015","journal-title":"J Clin Virol"},{"issue":"4","key":"pone.0313237.ref022","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.jaci.2010.11.041","article-title":"Host and viral factors associated with severity of human rhinovirus-associated infant respiratory tract illness","volume":"127","author":"EK Miller","year":"2011","journal-title":"J Allergy Clin Immunol"},{"issue":"1","key":"pone.0313237.ref023","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2011-0583","article-title":"Human rhinoviruses in severe respiratory disease in very low birth weight infants","volume":"129","author":"EK Miller","year":"2012","journal-title":"Pediatrics"},{"key":"pone.0313237.ref024","doi-asserted-by":"crossref","first-page":"104290","DOI":"10.1016\/j.jcv.2020.104290","article-title":"Epidemiological characteristics and clinical outcomes of human rhinovirus infections in a hospitalized population. Severity is independently linked to RSV coinfection and comorbidities","volume":"125","author":"A Comte","year":"2020","journal-title":"J Clin Virol"},{"issue":"2","key":"pone.0313237.ref025","doi-asserted-by":"crossref","first-page":"1800207","DOI":"10.1183\/13993003.00207-2018","article-title":"Rhinovirus is the most common virus and rhinovirus-C is the most common species in paediatric intensive care respiratory admissions","volume":"52","author":"DW Cox","year":"2018","journal-title":"Eur Respir J"},{"issue":"4","key":"pone.0313237.ref026","doi-asserted-by":"crossref","first-page":"755","DOI":"10.3390\/microorganisms10040755","article-title":"Molecular epidemiology of rhinovirus\/enterovirus and their role on cause severe and prolonged infection in hospitalized patients","volume":"10","author":"FAM Giardina","year":"2022","journal-title":"Microorganisms"},{"issue":"12","key":"pone.0313237.ref027","doi-asserted-by":"crossref","DOI":"10.1097\/INF.0000000000004097","article-title":"Comparing the clinical courses of children with human rhinovirus\/enterovirus to children with other respiratory viruses in the outpatient setting","volume":"42","author":"MU Jones","year":"2023","journal-title":"Pediatr Infect Dis J"},{"issue":"3","key":"pone.0313237.ref028","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/cid\/ciae216","article-title":"The impact of pretransplant respiratory virus detection on posttransplant outcomes in children undergoing hematopoietic cell transplantation","volume":"79","author":"SR Kim","year":"2024","journal-title":"Clin Infect Dis"},{"key":"pone.0313237.ref029","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jcv.2015.03.022","article-title":"Persistent rhinovirus infection in pediatric hematopoietic stem cell transplant recipients with impaired cellular immunity","volume":"67","author":"A Piralla","year":"2015","journal-title":"J Clin Virol"},{"issue":"8","key":"pone.0313237.ref030","doi-asserted-by":"crossref","DOI":"10.1111\/petr.13301","article-title":"Outcome of children with rhinovirus detection prior to allogeneic hematopoietic cell transplant","volume":"22","author":"C Mowrer","year":"2018","journal-title":"Pediatr Transplant"},{"issue":"1","key":"pone.0313237.ref031","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/jpids\/piad106","article-title":"Clinical outcomes of human rhinovirus\/enterovirus infection in pediatric hemopoietic cell transplant patients","volume":"13","author":"S Castejon-Ramirez","year":"2024","journal-title":"J Pediatric Infect Dis Soc"},{"issue":"2","key":"pone.0313237.ref032","doi-asserted-by":"crossref","DOI":"10.1111\/pai.14083","article-title":"Age-specific predictors of disease severity in children with respiratory syncytial virus infection beyond infancy and through the first 5\u2009years of age","volume":"35","author":"H Brenes-Chacon","year":"2024","journal-title":"Pediatr Allergy Immunol"},{"issue":"10","key":"pone.0313237.ref033","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1513\/AnnalsATS.202008-996OC","article-title":"Relationship of viral detection with duration of ventilation in critically Ill infants with lower respiratory tract infection","volume":"18","author":"BL Shutes","year":"2021","journal-title":"Ann Am Thorac Soc"},{"key":"pone.0313237.ref034","doi-asserted-by":"crossref","first-page":"105555","DOI":"10.1016\/j.jcv.2023.105555","article-title":"Increasing rhinovirus prevalence in paediatric intensive care patients since the SARS-CoV2 pandemic","volume":"166","author":"E Gil","year":"2023","journal-title":"J Clin Virol"},{"issue":"2","key":"pone.0313237.ref035","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/PCC.0000000000000308","article-title":"A multicenter outcomes analysis of children with severe rhino\/enteroviral respiratory infection","volume":"16","author":"MC Spaeder","year":"2015","journal-title":"Pediatr Crit Care Med"},{"issue":"2","key":"pone.0313237.ref036","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1177\/0009922818809483","article-title":"The resource burden of infections with rhinovirus\/enterovirus, influenza, and respiratory syncytial virus in children","volume":"58","author":"J Fine","year":"2019","journal-title":"Clin Pediatr (Phila)"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313237","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T14:02:25Z","timestamp":1747231345000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313237"}},"subtitle":[],"editor":[{"given":"Tai-Heng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,5,14]]},"references-count":36,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5,14]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0313237","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.23.24315981","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,14]]}}}