{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:28:27Z","timestamp":1788827307744,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,22]],"date-time":"2022-04-22T00:00:00Z","timestamp":1650585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["K08 HL133445"],"award-info":[{"award-number":["K08 HL133445"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart Lung and Blood Institute","doi-asserted-by":"publisher","award":["HL133445"],"award-info":[{"award-number":["HL133445"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI153337"],"award-info":[{"award-number":["R01 AI153337"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Influenza infection is a risk factor for invasive pulmonary aspergillosis in both immunocompetent and immunocompromised hosts. The purpose of this review is to highlight the epidemiology of influenza-associated invasive pulmonary aspergillosis and the mechanistic studies that have been performed to delineate how influenza increases susceptibility to this invasive fungal infection.<\/jats:p>","DOI":"10.3390\/jof8050428","type":"journal-article","created":{"date-parts":[[2022,4,23]],"date-time":"2022-04-23T21:39:45Z","timestamp":1650749985000},"page":"428","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mechanistic Basis of Super-Infection: Influenza-Associated Invasive Pulmonary Aspergillosis"],"prefix":"10.3390","volume":"8","author":[{"given":"Keven Mara","family":"Robinson","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh Medical Center; Pittsburgh, PA 15213, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1183\/09059180.00001011","article-title":"Pulmonary aspergillosis: A clinical review","volume":"20","author":"Kousha","year":"2011","journal-title":"Eur. 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Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13054-014-0722-7","article-title":"Epidemiology of invasive aspergillosis in critically ill patients: Clinical presentation, underlying conditions, and outcomes","volume":"19","author":"Taccone","year":"2015","journal-title":"Crit. Care"},{"key":"ref_5","doi-asserted-by":"crossref","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":"ref_6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1164\/rccm.201612-2540LE","article-title":"Influenza-Associated Aspergillosis in Critically Ill Patients","volume":"196","author":"Kolwijck","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"ofw171","DOI":"10.1093\/ofid\/ofw171","article-title":"Invasive Aspergillosis Associated with Severe Influenza Infections","volume":"3","year":"2016","journal-title":"Open Forum Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1111\/crj.12995","article-title":"Invasive pulmonary aspergillosis in patients with influenza infection: A retrospective study and review of the literature","volume":"13","author":"Huang","year":"2019","journal-title":"Clin. Respir. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1016\/j.jfma.2017.06.002","article-title":"Higher mortality of severe influenza patients with probable aspergillosis than those with and without other coinfections","volume":"116","author":"Ku","year":"2017","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1007\/s00134-012-2673-2","article-title":"Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: A retrospective study","volume":"38","author":"Wauters","year":"2012","journal-title":"Intensive Care Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.jinf.2020.07.036","article-title":"Early identification of patients with severe influenza-associated aspergillosis (IAA) in the intensive care unit\u2014An IAA prediction score system (Asper-PreSS)","volume":"81","author":"Huang","year":"2020","journal-title":"J. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wu, C.J., Cia, C.T., Wang, H.C., Chen, C.W., Lin, W.C., Lee, J.C., Chen, P.S., Hsieh, C.C., Li, W.T., and Su, P.L. (2022). Clinical and Microbiological Characteristics of Culture-Positive, Influenza-Associated Pulmonary Aspergillosis: A Single-Center Study in Southern Taiwan, 2016\u20132019. J. Fungi, 8.","DOI":"10.3390\/jof8010049"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1097\/CCM.0000000000004861","article-title":"The Extent of Aspergillosis in Critically Ill Patients With Severe Influenza Pneumonia: A Multicenter Cohort Study","volume":"49","author":"Coste","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1093\/cid\/ciaa007","article-title":"High Rates of Influenza-Associated Invasive Pulmonary Aspergillosis May Not Be Universal: A Retrospective Cohort Study from Alberta, Canada","volume":"71","author":"Schwartz","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s00134-016-4578-y","article-title":"Increased incidence of co-infection in critically ill patients with influenza","volume":"43","author":"Schultz","year":"2017","journal-title":"Intensive Care Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/j.chest.2020.06.010","article-title":"Influenza-Associated Aspergillosis: Nationwide Trends, Predictors and Outcomes from 2005 to 2014","volume":"158","author":"Sharma","year":"2020","journal-title":"Chest"},{"key":"ref_17","unstructured":"(2022, March 15). Influenza: Seasonal. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/influenza-(seasonal)."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1440-1843.2005.00593.x","article-title":"Invasive pulmonary aspergillosis associated with influenza B","volume":"10","author":"Hasejima","year":"2005","journal-title":"Respirology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3109\/13693786.2012.738312","article-title":"Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults","volume":"51","author":"Denning","year":"2013","journal-title":"Med. Mycol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nrd3074","article-title":"An insight into the antifungal pipeline: Selected new molecules and beyond","volume":"9","author":"Casadevall","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.tim.2010.02.004","article-title":"Therapy for fungal diseases: Opportunities and priorities","volume":"18","author":"Denning","year":"2010","journal-title":"Trends Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1007\/s00134-020-06091-6","article-title":"Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: An expert opinion","volume":"46","author":"Verweij","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1007\/s00134-021-06431-0","article-title":"Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): A randomised, open-label, proof-of-concept trial","volume":"47","author":"Vanderbeke","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S2213-2600(18)30332-1","article-title":"Let\u2019s add invasive aspergillosis to the list of influenza complications","volume":"6","author":"Lamoth","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.1097\/CCM.0000000000004093","article-title":"Corticosteroids as Adjunctive Therapy in the Treatment of Influenza: An Updated Cochrane Systematic Review and Meta-analysis","volume":"48","author":"Lansbury","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13054-015-0764-5","article-title":"Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis","volume":"19","author":"Zhang","year":"2015","journal-title":"Crit. Care"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7S","DOI":"10.1378\/chest.67.2_Supplement.7S","article-title":"The destruction of type 2 pneumocytes by airborne influenza PR8-A virus; its effect on surfactant and lecithin content of the pneumonic lesions of mice","volume":"67","author":"Loosli","year":"1975","journal-title":"Chest"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1164\/rccm.201910-1931OC","article-title":"Invasive Tracheobronchial Aspergillosis in Critically Ill Patients with Severe Influenza. A Clinical Trial","volume":"202","author":"Nyga","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1164\/rccm.202005-1883ED","article-title":"Invasive Aspergillus Tracheobronchitis Emerging as a Highly Lethal Complication of Severe Influenza","volume":"202","author":"Wauters","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1172\/JCI110489","article-title":"Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes","volume":"69","author":"Schaffner","year":"1982","journal-title":"J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"480","DOI":"10.4049\/jimmunol.2000067","article-title":"Influenza Suppresses Neutrophil Recruitment to the Lung and Exacerbates Secondary Invasive Pulmonary Aspergillosis","volume":"205","author":"Tobin","year":"2020","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nm1765","article-title":"Inhibition of pulmonary antibacterial defense by interferon-gamma during recovery from influenza infection","volume":"14","author":"Sun","year":"2008","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.4049\/jimmunol.1300014","article-title":"Depletion of alveolar macrophages during influenza infection facilitates bacterial superinfections","volume":"191","author":"Ghoneim","year":"2013","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.4049\/jimmunol.180.4.2562","article-title":"CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality","volume":"180","author":"Lin","year":"2008","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Seo, S.U., Kwon, H.J., Ko, H.J., Byun, Y.H., Seong, B.L., Uematsu, S., Akira, S., and Kweon, M.N. (2011). Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1001304"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"134","DOI":"10.4049\/jimmunol.1701406","article-title":"Effects of Influenza on Alveolar Macrophage Viability Are Dependent on Mouse Genetic Strain","volume":"201","author":"Califano","year":"2018","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1128\/IAI.01172-13","article-title":"Eosinophil deficiency compromises lung defense against Aspergillus fumigatus","volume":"82","author":"Lilly","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1080\/21505594.2021.1974327","article-title":"Early oseltamivir reduces risk for influenza-associated aspergillosis in a double-hit murine model","volume":"12","author":"Seldeslachts","year":"2021","journal-title":"Virulence"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100289","DOI":"10.1016\/j.xcrm.2021.100289","article-title":"Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis","volume":"2","author":"Dewi","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Seldeslachts, L., Jacobs, C., Tielemans, B., Vanhoffelen, E., Van der Sloten, L., Humblet-Baron, S., Naesens, L., Lagrou, K., Verbeken, E., and Wauters, J. (2021). Overcome Double Trouble: Baloxavir Marboxil Suppresses Influenza Thereby Mitigating Secondary Invasive Pulmonary Aspergillosis. J. Fungi, 8.","DOI":"10.3390\/jof8010001"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13054-021-03874-1","article-title":"Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: A European multicenter comparative cohort study","volume":"26","author":"Rouze","year":"2022","journal-title":"Crit. Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"ofab478","DOI":"10.1093\/ofid\/ofab478","article-title":"Invasive Pulmonary Aspergillosis Complicating Noninfluenza Respiratory Viral Infections in Solid Organ Transplant Recipients","volume":"8","author":"Apostolopoulou","year":"2021","journal-title":"Open Forum Infect. 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