{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:48:04Z","timestamp":1788295684903,"version":"build-2803163510"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"the Department of Science and Technology of Hubei Province","award":["#2022EHB035"],"award-info":[{"award-number":["#2022EHB035"]}]},{"name":"the Wuhan Municipal Health Commission","award":["#201441"],"award-info":[{"award-number":["#201441"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,2,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Acute respiratory infections (ARIs) in children present complex interactions between respiratory pathogens and host, contributing to high morbidity, hospitalization, and mortality. In this cross-sectional study, 2,044 pediatric in-patient samples were tested for 198 pathogens using targeted next-generation sequencing (tNGS). Pathogen spectrum and co-infection pattern were analyzed alongside blood-test results and clinical data. Pediatric ARIs presented staggered viral epidemics and age-specific infection patterns from 2022 to 2023. Viral infections were predominant in children under 3 years (67.5%). Specific viral-bacterial co-infections were associated with disease severity, including human metapneumovirus (HMPV)-\n                      <jats:italic toggle=\"yes\">Streptococcus pneumoniae<\/jats:italic>\n                      (OR = 3.172, 95% CI: 1.257\u20138.009), human parainfluenza virus (HPIV)-\n                      <jats:italic toggle=\"yes\">Fusobacterium nucleatum<\/jats:italic>\n                      (3.016, 1.051\u20138.653), and HPIV-\n                      <jats:italic toggle=\"yes\">S. pneumoniae<\/jats:italic>\n                      (2.825, 1.007\u20137.927). Subnormal levels of prealbumin and creatinine served as biomarkers for homeostasis disruption in viral-bacterial co-infections. From June to December 2023,\n                      <jats:italic toggle=\"yes\">Mycoplasma pneumoniae<\/jats:italic>\n                      (MP) became the dominant pathogen in preschool (31.3%) and school-age (45.3%) children. High MP loads were correlated with elevated eosinophil, IL-4, and IL-6 and decreased IgG and IL-2, linking to airway hyperreactivity and inflammation. At low MP loads, patients co-detected with human herpesvirus (HHV) (50.0%), or\n                      <jats:italic toggle=\"yes\">Haemophilus influenzae<\/jats:italic>\n                      (40.0%) had a high proportion of severe cases. This study delineated the complex pathogen landscape of pediatric ARIs and highlighted the major role of viral-bacterial and MP-bacterial co-infections. Monitoring these pathogens through tNGS can aid in precise diagnosis and targeted treatment to improve clinical outcomes in children.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Moving beyond the outdated \u201cone germ, one disease\u201d model, this study characterizes the etiological and epidemiological landscape and highlights co-infection patterns of virus-bacterium or MP-bacterium in 2044 pediatric respiratory in-patient children across three epidemic phases. Specific pathogen combinations are associated with clinical severity, as well as host immune and metabolic profiles. Our findings underscore the necessity of detecting pathogen-pathogen and host-pathogen dynamics, rather than individual pathogens, thereby informing precision diagnostics and targeted intervention strategies.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02275-25","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T20:26:36Z","timestamp":1767126396000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Pathogen landscape and synergistic interactions in pediatric ARIs: implications for broad-spectrum surveillance via targeted NGS"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-0261","authenticated-orcid":false,"given":"Jingjiao","family":"Zhou","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00e4hrk88","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology and Genetics, The College of Life Sciences and Health, Wuhan University of Science and Technology","place":["Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8147-8403","authenticated-orcid":false,"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00e4hrk88","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology and Genetics, The College of Life Sciences and Health, Wuhan University of Science and Technology","place":["Hubei, 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