{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T22:40:36Z","timestamp":1773268836450,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Human adenovirus (HAdV) is a significant cause of severe pneumonia in children that often causes sequelae. Although immune disorders are known to be associated with disease progression, comprehensive immunological predictors have not been identified. The purpose of this study was to explore the ability of multiple immunological indicators to predict severe adenovirus pneumonia (SAP) and to develop an immune-based nomogram for the early prediction of SAP in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study involved a retrospective analysis of children with adenovirus pneumonia who were hospitalized and received treatment at the Department of Respiratory Medicine, Capital Center for Children's Health, Capital Medical University between January 2017 and June 2025. Patients were stratified into mild and severe groups on the basis of clinical manifestations. They were subsequently randomly allocated at an 80:20 ratio into a training set and a cross-validation set for nomogram development and validation. R software (version 4.4.3) was used for statistical analysis, and effect sizes are expressed as odds ratios (ORs) and 95% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 1220 cases included, 357 (29.3%) were classified as severe. In both the training and cross-validation sets, patients with SAP were younger and had longer hospital stays (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). After the adjustments for age and sex, logistic regression in the training set revealed seven significant factors associated with SAP occurrence in children:\n                      <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n                      infection (OR\u2009=\u20091.372, 95% CI: 1.04\u20131.809,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001); complement component 3 (C3) (OR\u2009=\u20090.234, 95% CI: 0.132\u20130.417,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001) and 4 (C4) (OR\u2009=\u20090.075, 95% CI: 0.018\u20130.31,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001); immunoglobulin G (IgG) (OR\u2009=\u20091.049, 95% CI: 1.028\u20131.071,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001); and the percentages of CD3\n                      <jats:sup>+<\/jats:sup>\n                      [CD3\n                      <jats:sup>+<\/jats:sup>\n                      (%)] (OR\u2009=\u20090.965, 95% CI: 0.952\u20130.979,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), CD4\n                      <jats:sup>+<\/jats:sup>\n                      [CD4\n                      <jats:sup>+<\/jats:sup>\n                      (%)] (OR\u2009=\u20090.950, 95% CI: 0.934\u20130.967,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), and CD19\n                      <jats:sup>+<\/jats:sup>\n                      cells [CD19\n                      <jats:sup>+<\/jats:sup>\n                      (%)] (OR\u2009=\u20091.042, 95% CI: 1.028\u20131.057,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001). Furthermore, logistic regression of the validation set revealed C3, C4, IgG, CD3\n                      <jats:sup>+<\/jats:sup>\n                      (%), CD4\n                      <jats:sup>+<\/jats:sup>\n                      (%) and CD19\n                      <jats:sup>+<\/jats:sup>\n                      (%) as consistent predictors of SAP across datasets. Incorporating the significant factors improved model discrimination, increasing the area under the curve (AUC) from 0.627 to 0.836 in the training set and from 0.678 to 0.913 in the cross-validation set. The final nomogram model based on the significant factors demonstrated strong calibration and discrimination (C-index: 0.731 in the training set, 0.812 in the cross-validation set), supporting its potential for clinical risk stratification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identified and validated seven independent factors significantly associated with SAP in children. A nomogram incorporating these factors was developed and it demonstrated favourable discriminative performance and good calibration. The model exhibited high sensitivity and maintained high predictive accuracy across both datasets, indicating its potential clinical utility for individualized risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1742222","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:52:48Z","timestamp":1773211968000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Development and validation of an immune-based nomogram model for predicting severe adenovirus pneumonia in hospitalized children"],"prefix":"10.3389","volume":"14","author":[{"given":"Yuting","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics , Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics , Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenquan","family":"Niu","sequence":"additional","affiliation":[{"name":"Center for Evidence-Based Medicine, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Capital Center for Children\u2019s Health, Capital Institute of Pediatrics , Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.pedneo.2022.06.016","article-title":"Analysis of mortality risk factors in children with severe adenovirus pneumonia: a single-center retrospective study","volume":"64","author":"Xu","year":"2022","journal-title":"Pediatr Neonatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1207568","DOI":"10.3389\/fmed.2023.1207568","article-title":"Pediatric adenovirus pneumonia: clinical practice and current treatment","volume":"10","author":"Zhang","year":"2023","journal-title":"Front Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e10807","DOI":"10.1016\/j.heliyon.2022.e10807","article-title":"Identification of candidate biomarkers for severe adenovirus community-acquired pneumonia by proteomic approach","volume":"8","author":"Shi","year":"2022","journal-title":"Heliyon"},{"key":"B4","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1186\/s12890-023-02742-8","article-title":"A prediction model for acute respiratory distress syndrome in immunocompetent adults with adenovirus-associated pneumonia: a multicenter retrospective analysis","volume":"23","author":"Lin","year":"2023","journal-title":"BMC Pulm Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"54002","DOI":"10.3389\/fped.2021.654002","article-title":"Risk factors for the development of hemophagocytic lymphohistiocytosis in children with severe adenovirus pneumonia: a single-center retrospective study","volume":"9","author":"Zhang","year":"2021","journal-title":"Front Pediatr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"56679","DOI":"10.3389\/fped.2021.566797","article-title":"Analysis of clinical characteristics and risk factors of severe adenovirus pneumonia in children","volume":"9","author":"Zhong","year":"2021","journal-title":"Front Pediatr"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1122589","DOI":"10.3389\/fped.2023.1122589","article-title":"A nomogram for predicting severe adenovirus pneumonia in children","volume":"11","author":"Zhang","year":"2023","journal-title":"Front Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"63","DOI":"10.21037\/tp-23-312","article-title":"Clinical features and prediction of risk factors for severe adenovirus pneumonia in children","volume":"13","author":"Wang","year":"2024","journal-title":"Transl Pediatr"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.21037\/tp-22-585","article-title":"Interleukin-6 serum levels are independently associated with severe adenovirus pneumonia in children: a cross-sectional study","volume":"11","author":"Yao","year":"2023","journal-title":"Transl Pediatr"},{"key":"B10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s12879-023-08036-y","article-title":"Monocyte count is associated with the severity of human adenovirus pneumonia in hospitalized children aged less than 6 years","volume":"23","author":"Hu","year":"2023","journal-title":"BMC Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s12879-023-08132-z","article-title":"Comparisons of lymphocytes profiles and inflammatory cytokines levels in blood of patients with differed severity of infection by human adenovirus type 7","volume":"23","author":"Sun","year":"2023","journal-title":"BMC Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.3390\/v13091885","article-title":"Potential diagnostic and prognostic biomarkers for adenovirus respiratory infection in children and young adults","volume":"13","author":"Biserni","year":"2021","journal-title":"Viruses"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.3390\/v13122384","article-title":"Changes of host immunity mediated by IFN-\u03b3(+) CD8(+) T cells in children with adenovirus pneumonia in different severity of illness","volume":"13","author":"Zheng","year":"2021","journal-title":"Viruses"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1007\/s00431-023-05379-1","article-title":"Risk factors and prediction models for bronchiolitis obliterans after severe adenoviral pneumonia","volume":"183","author":"Wen","year":"2023","journal-title":"Eur J Pediatr"},{"key":"B15","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1111\/j.1651-2227.2012.02648.x","article-title":"Diagnosis and treatment of community-acquired pneumonia in children","volume":"101","author":"Korppi","year":"2012","journal-title":"Acta Paediatr"},{"key":"B16","doi-asserted-by":"publisher","first-page":"920","DOI":"10.3760\/cma.j.cn112140-20240728-00523","article-title":"Guidelines for the management of community-acquired pneumonia in children (2024 revision)","volume":"62","year":"2024","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"B17","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1093\/cid\/cir625","article-title":"Executive summary: the management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the pediatric infectious diseases society and the infectious diseases society of America","volume":"53","author":"Bradley","year":"2011","journal-title":"Clin Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1890\/13-1452.1","article-title":"Model selection for ecologists: the worldviews of AIC and BIC","volume":"95","author":"Aho","year":"2014","journal-title":"Ecology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1093\/oxfordjournals.aje.a009077","article-title":"Validity of methods for model selection, weighting for model uncertainty, and small sample adjustment in capture-recapture estimation","volume":"145","author":"Hook","year":"1997","journal-title":"Am J Epidemiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1093\/aje\/kwr086","article-title":"Evaluating the incremental value of new biomarkers with integrated discrimination improvement","volume":"174","author":"Kerr","year":"2011","journal-title":"Am J Epidemiol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1002\/sim.2929","article-title":"Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond","volume":"27","author":"Pencina","year":"2007","journal-title":"Stat Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1016\/j.eururo.2018.08.038","article-title":"Reporting and interpreting decision curve analysis: a guide for investigators","volume":"74","author":"Van Calster","year":"2018","journal-title":"Eur Urol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.bj.2021.08.009","article-title":"Human adenovirus infections in pediatric population\u2014an update on clinico-pathologic correlation","volume":"45","author":"Shieh","year":"2021","journal-title":"Biomed J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1626077","DOI":"10.3389\/fmicb.2025.1626077","article-title":"Respiratory microbiota, host immunity, respiratory viral infections and malignant tumors","volume":"16","author":"Jiang","year":"2025","journal-title":"Front Microbiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1552958","DOI":"10.3389\/fped.2025.1552958","article-title":"Research progress on human adenovirus sepsis","volume":"13","author":"Jianhua","year":"2025","journal-title":"Front Pediatr"},{"key":"B26","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1186\/s12887-024-05227-7","article-title":"Clinical features and risk factors for development of post-infectious bronchiolitis obliterans in children","volume":"24","author":"Xu","year":"2024","journal-title":"BMC Pediatr"},{"key":"B27","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.semnephrol.2013.08.001","article-title":"Overview of complement activation and regulation","volume":"33","author":"Noris","year":"2013","journal-title":"Semin Nephrol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/s41577-023-00858-w","article-title":"Antiviral neutralizing antibodies: from in vitro to in vivo activity","volume":"23","author":"Burton","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1093\/trstmh\/trv042","article-title":"Epidemiology of adenovirus respiratory infections among hospitalized children in seremban, Malaysia","volume":"109","author":"Foong Ng","year":"2015","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"B30","doi-asserted-by":"publisher","first-page":"300060521990244","DOI":"10.1177\/0300060521990244","article-title":"Clinical analysis of adenovirus pneumonia with pulmonary consolidation and atelectasis in children","volume":"49","author":"Lou","year":"2021","journal-title":"J Int Med Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12879-021-05903-4","article-title":"Adenovirus viremia may predict adenovirus pneumonia severity in immunocompetent children","volume":"21","author":"Zhang","year":"2021","journal-title":"BMC Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/s41522-025-00859-8","article-title":"Multi-omics analysis of host airway responses in pediatric Mycoplasma pneumoniae pneumonia reveals potential mechanisms of disease exacerbation caused by co-infection","volume":"11","author":"Li","year":"2025","journal-title":"NPJ Biofilms Microbiomes"},{"key":"B33","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.cyto.2014.09.011","article-title":"T cell subsets and their signature cytokines in autoimmune and inflammatory diseases","volume":"74","author":"Raphael","year":"2015","journal-title":"Cytokine"},{"key":"B34","doi-asserted-by":"publisher","first-page":"954936","DOI":"10.3389\/fimmu.2022.954936","article-title":"Role of B cells as antigen presenting cells","volume":"13","author":"Rastogi","year":"2022","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1186\/s13052-024-01771-1","article-title":"Risk factor analysis and prediction model construction for severe adenovirus pneumonia in children","volume":"50","author":"Liang","year":"2024","journal-title":"Ital J Pediatr"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1482787","DOI":"10.3389\/fcimb.2024.1482787","article-title":"Impact of co-infections and immune responses on clinical severity of human adenovirus 3 and 7 infections in hospitalized children with lower respiratory tract infections: a comparative study","volume":"14","author":"Ma","year":"2025","journal-title":"Front Cell Infect Microbiol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1002\/sim.7586","article-title":"A multiple-model generalisation of updating clinical prediction models","volume":"37","author":"Martin","year":"2017","journal-title":"Stat Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"g7594","DOI":"10.1136\/bmj.g7594","article-title":"Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement","volume":"350","author":"Collins","year":"2015","journal-title":"Br Med J"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1428090","DOI":"10.3389\/fped.2025.1428090","article-title":"Development and validation of a nomogram for predicting severe adenovirus pneumonia in children","volume":"13","author":"Yu","year":"2025","journal-title":"Front Pediatr"},{"key":"B40","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1186\/s12887-023-03883-9","article-title":"Construction and analysis of a nomogram prediction model for post-infectious bronchiolitis obliterans in children with adenovirus pneumonia after invasive mechanical ventilation","volume":"23","author":"Peng","year":"2023","journal-title":"BMC Pediatr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1742222\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:52:49Z","timestamp":1773211969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1742222\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":40,"alternative-id":["10.3389\/fped.2026.1742222"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1742222","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"article-number":"1742222"}}