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The CAPA all-cause mortality rate is approximately 50% and may be complicated by azole resistance. Genomic epidemiology can help shed light on the genetics of A. fumigatus causing CAPA, including the prevalence of resistance-associated alleles. We present a population genomic analysis of 21 CAPA isolates from four European countries with these isolates compared against 240 non-CAPA A. fumigatus isolates from a wider population. Bioinformatic analysis and antifungal susceptibility testing were performed to quantify resistance and identify possible genetically encoded azole-resistant mechanisms. The phylogenetic analysis of the 21 CAPA isolates showed that they were representative of the wider A. fumigatus population with no obvious clustering. The prevalence of phenotypic azole resistance in CAPA was 14.3% (n = 3\/21); all three CAPA isolates contained a known resistance-associated cyp51A polymorphism. The relatively high prevalence of azole resistance alleles that we document poses a probable threat to treatment success rates, warranting the enhanced surveillance of A. fumigatus genotypes in these patients. Furthermore, potential changes to antifungal first-line treatment guidelines may be needed to improve patient outcomes when CAPA is suspected.<\/jats:p>","DOI":"10.3390\/jof9111104","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T08:35:52Z","timestamp":1699864552000},"page":"1104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genomic Epidemiology Identifies Azole Resistance Due to TR34\/L98H in European Aspergillus fumigatus Causing COVID-19-Associated Pulmonary Aspergillosis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7337-1396","authenticated-orcid":false,"given":"Benjamin C.","family":"Simmons","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Global Infectious Disease Analysis, Imperial College London, London W2 1PG, UK"},{"name":"UK Health Security Agency, London EP14 4PU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1338-7860","authenticated-orcid":false,"given":"Johanna","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Global Infectious Disease Analysis, Imperial College London, London W2 1PG, UK"},{"name":"Department of Medical Microbiology, Radboudumc Center for Infectious Diseases (RCI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, St. James\u2019 Hospital Campus, Trinity College Dublin, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8600-9860","authenticated-orcid":false,"given":"Paul E.","family":"Verweij","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboudumc Center for Infectious Diseases (RCI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"},{"name":"Radboudumc-CWZ Center of Expertise for Mycology, Radboudumc Center for Infectious Diseases (RCI), Radboud University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands"},{"name":"Center for Infectious Disease Research, Diagnostics and Laboratory Surveillance, National for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Abdolrasouli","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Imperial College London, London W2 1NY, UK"},{"name":"Department of Infectious Diseases, King\u2019s College Hospital, London SE5 9RS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Schelenz","sequence":"additional","affiliation":[{"name":"Infection Sciences, King\u2019s College Hospital, London SE5 9RS, UK"},{"name":"School of Immunology & Microbial Sciences, King\u2019s College London, London WC2R 2LS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J.","family":"Hemmings","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Global Infectious Disease Analysis, Imperial College London, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1271-2550","authenticated-orcid":false,"given":"Alida Fe","family":"Talento","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, St. James\u2019 Hospital Campus, Trinity College Dublin, D08 NHY1 Dublin, Ireland"},{"name":"Department of Microbiology, Our Lady of Lourdes Hospital, A92 VW28 Drogheda, Ireland"},{"name":"Department of Microbiology, Royal College of Surgeons, D02 YN77 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auveen","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, St. James\u2019 Hospital, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Mansfield","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, St. James\u2019 Hospital Campus, Trinity College Dublin, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, St. James\u2019 Hospital Campus, Trinity College Dublin, D08 NHY1 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thijs","family":"Bosch","sequence":"additional","affiliation":[{"name":"Center for Infectious Disease Research, Diagnostics and Laboratory Surveillance, National for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-6402","authenticated-orcid":false,"given":"Matthew C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Global Infectious Disease Analysis, Imperial College London, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s11046-021-00573-x","article-title":"Fungal Genomics in Respiratory Medicine: What, How and When?","volume":"186","author":"Brackin","year":"2021","journal-title":"Mycopathologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cmi.2018.01.002","article-title":"Diagnosis and management of Aspergillus diseases: Executive summary of the 2017 ESCMID-ECMM-ERS guideline","volume":"24","author":"Ullmann","year":"2018","journal-title":"Clin. 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