{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T15:11:07Z","timestamp":1793373067986,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,3,23]],"date-time":"2024-03-23T00:00:00Z","timestamp":1711152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Human metapneumovirus (hMPV) is an important pathogen that causes both upper (URTIs) and lower respiratory tract infections (LRTIs) in children. The virus can be implicated in severe bronchiolitis and pneumonia, necessitating hospitalization, with certain cases requiring intensive care unit intervention. As part of a retrospective observational study, we aimed to identify indicators of severe hMPV respiratory tract infections in children referred to the University Children\u2019s Hospital Ljubljana and the Department of Infectious Diseases Ljubljana, Slovenia, during a recent outbreak. We analyzed clinical data from November 2022 to January 2023 and compared the characteristics of children presenting with URTIs and LRTIs. We also examined the characteristics of children with hMPV LRTIs, distinguishing between children with and without LRTI-associated hypoxemia. Of 78 hMPV-PCR-positive pediatric patients (mean age 3.1 years; 60.3% boys), 36% had a URTI, and 64% had an LRTI. Hospitalization was required in 64% (50\/78), with 42% (21\/50) requiring oxygen therapy. LRTI-associated hypoxemia was more common in patients with atopy who showed dyspnea, tachypnea, crackles, and wheezing on lung auscultation. In a multivariable logistic regression analysis, wheezing detected on lung auscultation was a significant predictive factor for hypoxemic hMPV-LRTI. Specifically, children presenting with wheezing were found to be ten times more likely to experience hypoxemia. Prematurity and chronic conditions did not influence the presentation or severity of hMPV infection. This study highlights wheezing and atopy as crucial indicators of severe hMPV LRTI in children, emphasizing the importance of early recognition and intervention.<\/jats:p>","DOI":"10.3390\/microorganisms12040641","type":"journal-article","created":{"date-parts":[[2024,3,25]],"date-time":"2024-03-25T14:00:23Z","timestamp":1711375223000},"page":"641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Exploring Clinical Predictors of Severe Human Metapneumovirus Respiratory Tract Infections in Children: Insights from a Recent Outbreak"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6343-6732","authenticated-orcid":false,"given":"Airin","family":"Veronese","sequence":"first","affiliation":[{"name":"Department of Paediatric Pulmonology, University Children\u2019s Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5621-7167","authenticated-orcid":false,"given":"Tina","family":"Ur\u0161i\u010d","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Immunology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Bizjak Vojinovi\u010d","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3903-5596","authenticated-orcid":false,"given":"Jasna","family":"Rodman Berlot","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pulmonology, University Children\u2019s Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"},{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ijid.2014.03.1394","article-title":"Human metapneumovirus: Review of an important respiratory pathogen","volume":"25","author":"Panda","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/89098","article-title":"A newly discovered human pneumovirus isolated from young children with respiratory tract disease","volume":"7","author":"Groen","year":"2001","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1080\/17843286.2018.1492509","article-title":"Epidemiology of RSV and hMPV in Belgium: A 10-year follow-up","volume":"74","author":"Cattoir","year":"2019","journal-title":"Acta Clin. Belg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1086\/379200","article-title":"Prevalence and Clinical Symptoms of Human Metapneumovirus Infection in Hospitalized Patients","volume":"188","author":"Fockens","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14022","DOI":"10.1038\/s41598-019-50340-8","article-title":"Epidemiology, evolution and transmission of human metapneumovirus in Guangzhou China, 2013\u20132017","volume":"9","author":"Yi","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1128\/CMR.00015-11","article-title":"Human metapneumovirus: Lessons learned over the first decade","volume":"24","author":"Schildgen","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1056\/NEJMoa1204630","article-title":"Burden of Human Metapneumovirus Infection in Young Children","volume":"368","author":"Edwards","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1055\/s-0036-1584800","article-title":"Metapneumovirus Infections and Respiratory Complications","volume":"37","author":"Esposito","year":"2016","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/ppul.20597","article-title":"Human metapneumovirus bronchiolitis in infancy is an important risk factor for asthma at age 5","volume":"42","author":"Calvo","year":"2007","journal-title":"Pediatr. Pulmonol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.3201\/eid1007.030633","article-title":"Human metapneumovirus and chronic obstructive pulmonary disease","volume":"10","author":"Vicente","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1093\/jpids\/piaa118","article-title":"Human Metapneumovirus Infection and Genotyping of Infants in Rural Nepal","volume":"10","author":"Perchetti","year":"2021","journal-title":"J. Pediatr. Infect. Dis. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2004173","DOI":"10.1183\/13993003.04173-2020","article-title":"European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years","volume":"58","author":"Gaillard","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jev\u0161nik Virant, M., Ur\u0161i\u010d, T., Kogoj, R., Korva, M., Petrovec, M., and Av\u0161i\u010d-\u017dupanc, T. (2022). Evaluation of Two Broadly Used Commercial Methods for Detection of Respiratory Viruses with a Recently Added New Target for Detection of SARS-CoV-2. Viruses, 14.","DOI":"10.3390\/v14071530"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"634","DOI":"10.3201\/eid0906.030017","article-title":"Human Metapneumovirus Infections in Hospitalized Children","volume":"9","author":"Boivin","year":"2003","journal-title":"Emerg. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"195","DOI":"10.7883\/yoken.66.195","article-title":"Characteristics of Human Metapneumovirus Infection Prevailing in Hospital Wards Housing Patients with Severe Disabilities","volume":"66","author":"Matsuda","year":"2013","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1056\/NEJMoa025472","article-title":"Human Metapneumovirus and Lower Respiratory Tract Disease in Otherwise Healthy Infants and Children","volume":"350","author":"Williams","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1111\/crj.13261","article-title":"Human bocavirus and metapneumovirus in acute wheezing in children\u2014Is there a link with atopy?","volume":"14","author":"Sobkowiak","year":"2020","journal-title":"Clin. Respir. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1164\/rccm.200802-309OC","article-title":"Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children","volume":"178","author":"Jackson","year":"2008","journal-title":"Am. J. Respir. Crit."},{"key":"ref_19","first-page":"329","article-title":"Prevalence of respiratory viruses in wheezing children not older than 24 months of age","volume":"153","author":"Montero","year":"2017","journal-title":"Gac. Med. Mex."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.jaci.2006.12.669","article-title":"Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma","volume":"119","author":"Kusel","year":"2007","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1086\/444392","article-title":"Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults","volume":"192","author":"Williams","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.jaci.2005.02.001","article-title":"Human metapneumovirus infection in children hospitalized for wheezing","volume":"115","author":"Williams","year":"2005","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1097\/INF.0000000000002038","article-title":"Burden of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Asthmatic Children","volume":"37","author":"Furuta","year":"2018","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.7883\/yoken.JJID.2018.480","article-title":"Comparison of Clinical Characteristics of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Hospitalized Young Children","volume":"72","author":"Taniguchi","year":"2019","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1086\/504262","article-title":"Human Metapneumovirus Infection Induces Long-Term Pulmonary Inflammation Associated with Airway Obstruction and Hyperresponsiveness in Mice","volume":"193","author":"Hamelin","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/S0002-9440(10)63750-9","article-title":"Experimental Human Metapneumovirus Infection of Cynomolgus Macaques (Macaca fascicularis) Results in Virus Replication in Ciliated Epithelial Cells and Pneumocytes with Associated Lesions throughout the Respiratory Tract","volume":"164","author":"Kuiken","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10944","DOI":"10.1128\/JVI.79.17.10944-10951.2005","article-title":"The Cotton Rat (Sigmodon hispidus) Is a Permissive Small Animal Model of Human Metapneumovirus Infection, Pathogenesis, and Protective Immunity","volume":"79","author":"Williams","year":"2005","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.antiviral.2004.12.009","article-title":"Development of a cotton rat-human metapneumovirus (hMPV) model for identifying and evaluating potential hMPV antivirals and vaccines","volume":"66","author":"Wyde","year":"2005","journal-title":"Antivir. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s10024-004-1011-2","article-title":"Pathology of human metapneumovirus infection: Insights into the pathogenesis of a newly identified respiratory virus","volume":"7","author":"Vargas","year":"2004","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e01068-20","DOI":"10.1128\/JVI.01068-20","article-title":"Respiratory Syncytial Virus and Human Metapneumovirus Infections in Three-Dimensional Human Airway Tissues Expose an Interesting Dichotomy in Viral Replication, Spread, and Inhibition by Neutralizing Antibodies","volume":"94","author":"Kinder","year":"2020","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"G\u00e1lvez, N.M.S., Andrade, C.A., Pacheco, G.A., Soto, J.A., Stranger, V., Rivera, T., V\u00e1squez, A.E., and Kalergis, A.M. (2021). Host components that modulate the disease caused by hMPV. Viruses, 13.","DOI":"10.3390\/v13030519"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1042\/CS20160011","article-title":"Role of human metapneumovirus and respiratory syncytial virus in asthma exacerbations: Where are we now?","volume":"131","author":"Rudd","year":"2017","journal-title":"Clin. Sci."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/4\/641\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:18:25Z","timestamp":1760105905000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/12\/4\/641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,23]]},"references-count":32,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["microorganisms12040641"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms12040641","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,23]]}}}