{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:10:42Z","timestamp":1792177842242,"version":"4.4.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Rationale<\/jats:title><jats:p>Influenza-associated pulmonary aspergillosis (IAPA) is a great clinical challenge, which has high morbidity and mortality in severe influenza infections. Unlike invasive pulmonary aspergillosis (IPA), IAPA often occurs in immunocompetent hosts. That IAPA lacks of specific manifestations makes it difficult to diagnose and causes a high mortality rate, which is becoming challenges toclinicians. Exploring the clinical characteristics of IAPA in depth is of great significance for guiding clinical practice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To determine the clinical features of IAPA in order to support appropriate clinical management of this public health threat.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective multicenter cohort study was conducted. The clinical characteristics, risk factors, diagnostic methods, treatment, and prognosis data of the participants were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Diabetes and lymphopenia were important risk factors for IAPA. Pulmonary imaging showed that IAPA patients had more nodular lesions in the lungs, and a higher proportion of them were accompanied by cavitary lesions. The galactomannan (GM) test in bronchoalveolar lavage fluid (BALF) showed high sensitivity and specificity for diagnosing IPA. The positive rate of <jats:italic>Aspergillus<\/jats:italic> culture was relatively low, while microbiology rapid on-site evaluation (M-ROSE) could effectively detect mould with high specificity. The targeted next generation sequencing (tNGS) had important value in detecting <jats:italic>Aspergillus<\/jats:italic> with a sensitivity of 100% and a specificity of 86.7%. Both IAPA and Non-IAPA patients had a higher rate of co-infections, with a significantly higher co-infection rate of atypical pathogens in the IAPA group compared to the Non-IAPA group. The average treatment course for IAPA patients in the present study (32.2 \u00b1 4.8d) was greatly shorter than the course specified in the IDSA (2016) guideline. The neutrophil to lymphocyte ratio (NLR) could effectively predict the prognosis of IAPA patients (cutoff value of NLR was 17.70, corresponding to a sensitivity of 0.87 and a specificity of 0.97).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Diabetes and lymphopenia were important risk factors for IAPA. The comprehensive application of serum and BALF GM, M-ROSE and tNGS could significantly improve the detection rate of <jats:italic>Aspergillus<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1648547","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T08:11:10Z","timestamp":1760602270000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical features of influenza-associated pulmonary aspergillosis: a retrospective multicenter cohort study"],"prefix":"10.3389","volume":"15","author":[{"given":"Jia-Xin","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Rong","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Chao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1186\/s12890-024-03281-6","article-title":"Patients with influenza admitted to a tertiary-care hospital in Riyadh between 2018 and 2022: characteristics, outcomes and factors associated with ICU admission and mortality","volume":"24","author":"Al-Dorzi","year":"2024","journal-title":"BMC Pulm Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"S79","DOI":"10.1093\/cid\/ciaa1855","article-title":"Guidance on imaging for invasive pulmonary aspergillosis and mucormycosis: from the imaging working group for the revision and update of the consensus definitions of fungal disease from the EORTC\/MSGERC","volume":"72","author":"Alexander","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s00134-024-07341-7","article-title":"Invasive Fungal Diseases in Adult Patients in Intensive Care Unit (FUNDICU): 2024 consensus definitions from ESGCIP, EFISG, ESICM, ECMM, MSGERC, ISAC, and ISHAM","volume":"50","author":"Bassetti","year":"2024","journal-title":"Intensive Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e344","DOI":"10.1016\/S1473-3099(17)30304-3","article-title":"Candida and invasive mould diseases in non-neutropenic critically ill patients and patients with haematological cancer","volume":"17","author":"Colombo","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1164\/rccm.202410-2045ST","article-title":"Treatment of invasive pulmonary aspergillosis and preventive and empirical therapy for invasive candidiasis in adult pulmonary and critical care patients. An official American thoracic society clinical practice guideline","volume":"211","author":"Epelbaum","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/S2213-2600(24)00151-6","article-title":"Influenza-associated and COVID-19-associated pulmonary aspergillosis in critically ill patients","volume":"12","author":"Feys","year":"2024","journal-title":"Lancet Respir. Med."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1007\/s10096-025-05143-3","article-title":"Clinical characteristics and co-infection analysis of influenza a virus in pediatric respiratory infections: a study based on tNGS technology","volume":"44","author":"Fu","year":"2025","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1007\/s00125-024-06102-x","article-title":"Diabetes and infection: review of the epidemiology, mechanisms and principles of treatment","volume":"67","author":"Holt","year":"2024","journal-title":"Diabetologia"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2025.107671","article-title":"Influenza virus: Genomic insights, evolution, and its clinical presentation","volume":"205","author":"Jain","year":"2025","journal-title":"Microb. Pathog."},{"key":"B11","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.jinf.2016.10.010","article-title":"Pulmonary immune responses against Aspergillus fumigatus are characterized by high frequencies of IL-17 producing T-cells","volume":"74","author":"Jolink","year":"2017","journal-title":"J. Infect."},{"key":"B12","doi-asserted-by":"publisher","first-page":"d930","DOI":"10.2741\/1098","article-title":"T lymphocyte responses are critical determinants in the pathogenesis and resistance to mycoplasma respiratory disease","volume":"8","author":"Jones","year":"2003","journal-title":"Front. Biosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1111\/myc.13056","article-title":"Invasive pulmonary aspergillosis treatment duration in haematology patients in Europe: An EFISG, IDWP-EBMT, EORTC-IDG and SEIFEM survey","volume":"63","author":"Lanternier","year":"2020","journal-title":"Mycoses"},{"key":"B14","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.chest.2023.09.019","article-title":"Prevalence, risk factors, clinical features, and outcome of influenza-associated pulmonary aspergillosis in critically ill patients: A systematic review and meta-analysis","volume":"165","author":"Lu","year":"2024","journal-title":"Chest"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/v10080407","article-title":"Mutation and epistasis in influenza virus evolution","volume":"10","author":"Lyons","year":"2018","journal-title":"Viruses"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1397733","article-title":"Clinical utility of metagenomic next-generation sequencing in the diagnosis of invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease patients in the intensive care unit","volume":"14","author":"Niu","year":"2024","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1097\/QCO.0000000000000523","article-title":"Biomarkers of fungal lung infection","volume":"32","author":"Paiva","year":"2019","journal-title":"Curr. Opin. Infect. Dis."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1093\/cid\/ciw326","article-title":"Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the infectious diseases society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1086\/323900","article-title":"The impact of culture isolation of Aspergillus species: a hospital-based survey of aspergillosis","volume":"33","author":"Perfect","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"B20","first-page":"149","article-title":"The accuracy of serum galactomannan assay in diagnosing invasive pulmonary aspergillosis","volume":"9","author":"Sarrafzadeh","year":"2010","journal-title":"Iran J. Allergy Asthma Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1016\/S2213-2600(18)30274-1","article-title":"Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study","volume":"6","author":"Schauwvlieghe","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.21037\/atm-21-5465","article-title":"Application of microbiological rapid on-site evaluation in respiratory intensive care units: a retrospective study","volume":"10","author":"Tao","year":"2022","journal-title":"Ann. Transl. Med."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab091","article-title":"Invasive aspergillosis after influenza and other viral respiratory infections among intensive care unit patients in a commercially insured population in the United States 2013\u20132018","volume":"8","author":"Toda","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1093\/infdis\/jiaf044","article-title":"Performance of mp-tNGS in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in nonneutropenic patients","volume":"231","author":"Wang","year":"2025","journal-title":"J. Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myaa077","article-title":"Prospective observational study of respiratory Aspergillus colonization or disease in patients with various stages of chronic obstructive pulmonary disease utilizing culture versus nonculture techniques","author":"Waqas","year":"2020","journal-title":"Med. Mycol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1336456","article-title":"Predictive value of the neutrophil-to-lymphocyte ratio in the prognosis and risk of death for adult sepsis patients: a meta-analysis","volume":"15","author":"Wu","year":"2024","journal-title":"Front. Immunol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2020.115274","article-title":"Diagnostic value of galactomannan in serum and bronchoalveolar lavage fluid for invasive pulmonary aspergillosis in non-neutropenic patients","volume":"99","author":"Wu","year":"2021","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1177\/09622802241295319","article-title":"Youden index estimation based on group-tested data","volume":"34","author":"Yang","year":"2025","journal-title":"Stat. Methods Med. Res."},{"key":"B29","first-page":"5","article-title":"Ratio of neutrophil to lymphocyte counts\u2013rapid and simple parameter of systemic inflammation and stress in critically ill","volume":"102","author":"Zahorec","year":"2001","journal-title":"Bratisl Lek Listy"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3390\/jof11010070","article-title":"Invasive aspergillosis in the intensive care","volume":"11","author":"Zubovskaia","year":"2025","journal-title":"Unit J. Fungi (Basel)"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1648547\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T08:11:14Z","timestamp":1760602274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1648547\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":30,"alternative-id":["10.3389\/fcimb.2025.1648547"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1648547","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,15]]},"article-number":"1648547"}}