{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:47:37Z","timestamp":1791557257795,"version":"4.3.4"},"reference-count":102,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As the global SARS-CoV-2 pandemic continues to plague healthcare systems, it has become clear that opportunistic pathogens cause a considerable proportion of SARS-CoV-2-associated mortality and morbidity cases. Of these, Covid-Associated Pulmonary Aspergilliosis (CAPA) is a major concern with evidence that it occurs in the absence of traditional risk factors such as neutropenia and is diagnostically challenging for the attending physician. In this review, we focus on the immunopathology of SARS-CoV-2 and how this potentiates CAPA through dysregulation of local and systemic immunity as well as the unintended consequences of approved COVID treatments including corticosteroids and IL-6 inhibitors. Finally, we will consider how knowledge of the above may aid in the diagnosis of CAPA using current diagnostics and what treatment should be instituted in probable and confirmed cases.<\/jats:p>","DOI":"10.3390\/ijms23063228","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:30:14Z","timestamp":1647811814000},"page":"3228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SARS-CoV-2 Associated Immune Dysregulation and COVID-Associated Pulmonary Aspergilliosis (CAPA): A Cautionary Tale"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7159-7033","authenticated-orcid":false,"given":"Dominic Adam","family":"Worku","sequence":"first","affiliation":[{"name":"Infectious Diseases and Microbiology Department, Morriston Hospital, Swansea University Health Board, Swansea SA6 6NL, UK"},{"name":"Public Health Wales, Cardiff CF10 4BZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Schwartz, D.A., and Graham, A.L. (2020). Potential Maternal and Infant Outcomes from (Wuhan) Coronavirus 2019-nCoV Infecting Pregnant Women: Lessions from SARS, MERS and Other Human Coronavirus Infection. Viruses, 2.","DOI":"10.3390\/v12020194"},{"key":"ref_2","unstructured":"(2022, February 19). Weekly Epidemiological Update on COVID-19- 15 February 2022. Available online: https:\/\/www.who.int\/publications\/m\/item\/weekly-epidemiological-update-on-covid-19---15-february-2022."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Block, H., and Zarbock, A. (2021). A Fragile Balance: Does Neutrophil Extracellular Trap Formation Drive Pulmonary Disease Progression?. Cells, 10.","DOI":"10.3390\/cells10081932"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Aan, F.J., Glibetic, N., Montoya-Uribe, V., and Matter, M.L. (2021). COVID-19 and the Microbiome: The Gut-Lung Connection. Ref. Modul. Food Sci.","DOI":"10.1016\/B978-0-12-819265-8.00048-6"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"108255","DOI":"10.1016\/j.intimp.2021.108255","article-title":"The triumvirate of NF-\u03baB, inflammation and cytokine storm in COVID-19","volume":"101","author":"Attiq","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1111\/bjh.17664","article-title":"COVID-19 and immunothrombosis: Emerging understanding and clinical management","volume":"194","author":"Shaw","year":"2021","journal-title":"Br. J. Haematol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Musuuza, J.S., Watson, L., Parmasad, V., Putman-Buehler, N., Christensen, L., and Safdar, N. (2021). Prevalence and outcomes of co-infection and superinfection with SARS-CoV-2 and other pathogens: A systematic review and meta-analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251170"},{"key":"ref_8","first-page":"144","article-title":"Prevalence of opportunistic invasive aspergillosis in COVID-19 patients with severe pneumonia","volume":"64","author":"Carrillo","year":"2020","journal-title":"Mycoses"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Roudbary, M., Kumar, S., Kumar, A., \u010cern\u00e1kov\u00e1, L., Nikoomanesh, F., and Rodrigues, C.F. (2021). Overview on the Prevalence of Fungal Infections, Immune Response, and Microbiome Role in COVID-19 Patients. J. Fungi, 7.","DOI":"10.3390\/jof7090720"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Apostolopoulou, A., Garrigos, Z.E., Vijayvargiya, P., Lerner, A.H., and Farmakiotis, D. (2020). Invasive Pulmonary Aspergillosis in Patients with SARS-CoV-2 Infection: A Systematic Review of the Literature. Diagnostics, 10.","DOI":"10.3390\/diagnostics10100807"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Khan, A.A., Farooq, F., Jain, S.K., Golinska, P., and Rai, M. (2021). Comparative Host\u2013Pathogen Interaction Analyses of SARS-CoV-2 and Aspergillus fumigatus, and Pathogenesis of COVID-19-Associated Aspergillosis. Microb. Ecol., 1\u20139.","DOI":"10.1007\/s00248-021-01913-6"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Feys, S., Almyroudi, M.P., Braspenning, R., Lagrou, K., Spriet, I., Dimopoulos, G., and Wauters, J. (2021). A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis (CAPA). J. Fungi, 7.","DOI":"10.3390\/jof7121067"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Salazar, F., Bignell, E., Brown, G.D., Cook, P.C., and Warris, A. (2022). Pathogenesis of Respiratory Viral and Fungal Coinfections. Clin. Microbiol. Rev., 35.","DOI":"10.1128\/CMR.00094-21"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Reizine, F., Pinceaux, K., Lederlin, M., Autier, B., Guegan, H., Gacouin, A., Luque-Paz, D., Boglione-Kerrien, C., Bacle, A., and Le Dar\u00e9, B. (2021). Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?. J. Fungi, 7.","DOI":"10.21203\/rs.3.rs-331976\/v1"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ezeokoli, O., Gcilitshana, O., and Pohl, C. (2021). Risk Factors for Fungal Co-Infections in Critically Ill COVID-19 Patients, with a Focus on Immunosuppressants. J. Fungi, 7.","DOI":"10.3390\/jof7070545"},{"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":"5","author":"Sharma","year":"2020","journal-title":"Chest"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kwon-Chung, K.J., and Sugui, J.A. (2013). Aspergillus fumigatus\u2014What Makes the Species a Ubiquitous Human Fungal Pathogen?. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003743"},{"key":"ref_18","first-page":"271","article-title":"Invasive Fungal Infection New Treatments to Meet New Challenges","volume":"116","author":"Wagener","year":"2019","journal-title":"Dtsch. Arztebl. Int."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Casalini, G., Giacomelli, A., Ridolfo, A., Gervasoni, C., and Antinori, S. (2021). Invasive Fungal Infections Complicating COVID-19: A Narrative Review. J. Fungi, 7.","DOI":"10.3390\/jof7110921"},{"key":"ref_20","unstructured":"Cascella, M., Rajnik, M., Aleem, A., Dulebohn, S.C., and Napoli, R.D. (2022, February 21). Features, Evaluation, and Treatment of Coronavirus (COVID-19), Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554776\/."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41577-021-00656-2","article-title":"Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses\u2013are we our own worst enemy?","volume":"22","author":"Wong","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_22","first-page":"75","article-title":"Immunological response to COVID-19 and its role as a predisposing factor in invasive aspergillosis","volume":"6","author":"Tavakoli","year":"2020","journal-title":"Curr. Med. Mycol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1158\/2159-8290.CD-20-0451","article-title":"TMPRSS2 and COVI-19: Serendipity or opportunity for intervention?","volume":"10","author":"Stopsack","year":"2020","journal-title":"Cancer Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/s41581-020-00357-4","article-title":"Immunity, endothelial injury and complement-induced coagulopathy in COVID-19","volume":"17","author":"Perico","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s12276-021-00602-1","article-title":"Innate immune sensing of coronavirus and viral evasion strategies","volume":"53","author":"Kasuga","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_26","first-page":"9647","article-title":"Activation of the TLR4\/MyD88 signaling pathway contributes to the development of human hepatocellular carcinoma via upregulation of IL-23 and IL-17A","volume":"15","author":"Kang","year":"2018","journal-title":"Oncol Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8874339","DOI":"10.1155\/2021\/8874339","article-title":"COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation","volume":"2021","author":"Aboudounya","year":"2021","journal-title":"Mediat. Inflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/j.cell.2005.08.012","article-title":"Identification and characterization of MAVS, a mitochondrial antiviral signalling protein that activates NF-kappaB and IRF3","volume":"122","author":"Seth","year":"2005","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1089\/jir.2010.0120","article-title":"New insights into the role of RNase L in innate immunity","volume":"37","author":"Chakrabarti","year":"2011","journal-title":"J. Interferon Cytokine Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.cytogfr.2021.03.006","article-title":"COVID-19 as a mediator of interferon deficiency and hyperinflammation: Rationale for the use of JAK1\/2 inhibitors in combination with interferon","volume":"60","author":"Hasselbalch","year":"2021","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S2666-5247(21)00027-6","article-title":"Interferon antagonism by SARS-CoV-2: A functional study using reverse genetics","volume":"2","author":"Schroeder","year":"2021","journal-title":"Lancet Microbe"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"198074","DOI":"10.1016\/j.virusres.2020.198074","article-title":"The ORF6, ORF8 and Nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon-signalling pathway","volume":"286","author":"Li","year":"2020","journal-title":"Virus Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/path.5642","article-title":"COVID-19: Immunopathology, pathophysiological mechanisms, and treatment options","volume":"254","author":"Binkhorst","year":"2021","journal-title":"J. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S2665-9913(21)00034-5","article-title":"Type I interferon, anti-interferon antibodies, and COVID-19","volume":"3","author":"Calabrese","year":"2021","journal-title":"Lancet Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/S2213-2600(21)00384-2","article-title":"Efficacy of interferon beta-1a plus Remdesevir compared with Remdesevir alone in hospitalised adults with COVID-19: A double bind, randomised, placebo-controlled, phase 3 trial","volume":"9","author":"Kalil","year":"2021","journal-title":"Lancet Respir Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1080\/20009666.2021.1984644","article-title":"Efficacy of subcutaneous interferon-beta in COVID-19: A meta-analysis and systematic review","volume":"11","author":"Asif","year":"2021","journal-title":"J. Community Hosp. Intern. Med. Perspect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4694","DOI":"10.1172\/JCI138554","article-title":"Impaired immune cell cytotoxicity in severe COVID-19 is IL-6 dependent","volume":"130","author":"Mazzoni","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.3389\/fimmu.2020.01446","article-title":"The COVID-19 Cytokine Storm; What We Know So Far","volume":"11","author":"Ragab","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.kint.2020.05.013","article-title":"The case of complement activation in COVID-19 multiogan impact","volume":"98","author":"Noris","year":"2020","journal-title":"Kidney Int."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Janiuk, K., Jab\u0142o\u0144ska, E., and Garley, M. (2021). Significance of NETs Formation in COVID-19. Cells, 10.","DOI":"10.3390\/cells10010151"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Veras, F.P., Pontelli, M.C., Silva, C.M., Toller-Kawahisa, J.E., de Lima, M., Nascimento, D.C., Schneider, A.H., Caetit\u00e9, D., Tavares, L.A., and Paiva, I.M. (2020). SARS-CoV-2\u2013triggered neutrophil extracellular traps mediate COVID-19 pathology. J. Exp. Med., 217.","DOI":"10.1084\/jem.20201129"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1182\/blood.2020007008","article-title":"Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome","volume":"10","author":"Middleton","year":"2020","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"708302","DOI":"10.3389\/fphar.2021.708302","article-title":"NETosis and the Immune System in COVID-19: Mechanisms and Potential Treatments","volume":"12","author":"Gillot","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100741","DOI":"10.1016\/j.jbior.2020.100741","article-title":"Devilishly radical NETwork in COVID-19: Oxidative stress, neutrophil extracellular traps (NETs), and T cell suppression","volume":"77","author":"Raftery","year":"2020","journal-title":"Adv. Biol. Regul."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1002\/1873-3468.13744","article-title":"The complement system in Aspergillus fumigatus infections and its crosstalk with pentraxins","volume":"594","author":"Parente","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1093\/femsre\/fuv018","article-title":"The innate immune response to Aspergillus fumigatus at the alveolar surface","volume":"39","author":"Margalit","year":"2015","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e13530","DOI":"10.1111\/eci.13530","article-title":"Circulating pentraxin 3 in severe COVID-19 or other pulmonary sepsis","volume":"51","author":"Protti","year":"2021","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Costantini, C., Van De Veerdonk, F.L., and Romani, L. (2020). Covid-19-Associated Pulmonary Aspergillosis: The Other Side of the Coin. Vaccines, 8.","DOI":"10.3390\/vaccines8040713"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/QCO.0b013e328348b159","article-title":"Immune responses against Aspergillus Fumigatus: What have we learned?","volume":"24","author":"Cramer","year":"2011","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.mib.2021.04.006","article-title":"Invasive pulmonary aspergillosis associated with viral pneumonitis","volume":"62","author":"Dewi","year":"2021","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S2213-2600(21)00442-2","article-title":"Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: The French multicentre MYCOVID study","volume":"10","author":"Gangneux","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e3606","DOI":"10.1093\/cid\/ciaa1065","article-title":"Epidemiology of Invasive Pulmonary Aspergillosis Among Intubated Patients With COVID-19: A Prospective Study","volume":"73","author":"Bartoletti","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"753659","DOI":"10.3389\/fmed.2021.753659","article-title":"Risk Factors for Invasive Aspergillosis in Patients Admitted to the Intensive Care Unit with Coronavirus Disease 2019: A Multicenter Retrospective Study","volume":"8","author":"Xu","year":"2021","journal-title":"Front. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1186\/s13613-021-00923-4","article-title":"Risk factors for invasive aspergillosis in ICU patients with COVID-19: Current insights and new key elements","volume":"11","author":"Montrucchio","year":"2021","journal-title":"Ann. Intensiv. Care"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jmii.2020.09.004","article-title":"COVID-19 associated with pulmonary aspergillosis: A literature review","volume":"54","author":"Lai","year":"2020","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Prattes, J., Wauters, J., Giacobbe, D.R., Salmanton-Garc\u00eda, J., Maertens, J., Bourgeois, M., Reynders, M., Rutsaert, L., Van Regenmortel, N., and Lormans, P. (2021). Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients\u2014A multinational observational study by the European Confederation of Medical Mycology. Clin. Microbiol. Infect.","DOI":"10.2139\/ssrn.3868099"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.cmi.2020.12.018","article-title":"Antibiotic prescribing in patients with COVID-19: Rapid review and meta-analysis","volume":"27","author":"Langford","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1093\/cid\/ciaa1298","article-title":"A national Strategy to Diagnose Coronavirus Disease 2019-Associated Invasive Fungal Disease in the Intensive Care Unit","volume":"73","author":"White","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1086\/525044","article-title":"Gliotoxin Production in Aspergillus fumigatus Contributes to Host-Specific Differences in Virulence","volume":"197","author":"Spikes","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ijmm.2007.04.006","article-title":"Gliotoxin production by clinical and environmental Aspergillus fumigatus strains","volume":"298","author":"Kupfahl","year":"2008","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"The Recovery Collaborative Group (2021). Dexamethasone in Hospitalized Patients with COVID-19. NEJM, 384, 693\u2013704.","DOI":"10.1056\/NEJMoa2021436"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1016\/S0140-6736(03)14904-5","article-title":"Glucocorticoids and invasive fungal infections","volume":"362","author":"Lionakis","year":"2003","journal-title":"Lancet"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1099\/13500872-140-9-2475","article-title":"Hydrocortisone-enhanced growth of Aspergillus simplications for pathogenesis","volume":"140","author":"Ng","year":"1994","journal-title":"Microbiology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.autrev.2008.07.010","article-title":"Use of glucocorticoids and risk of infections","volume":"8","author":"Cutulo","year":"2008","journal-title":"Autoimmun. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chen, W., Yin, C., Zhong, M., Hu, B., Gao, X., Zhang, K., Liu, Y., and Zhuang, G. (Res. Sq., 2021). Incidence, Risk Factors and Outcomes of Patients with COVID-19-Associated Pulmonary Aspergillosis (CAPA) in Intensive Care Units: A systematic Review and Meta-analysis of 29 Cohort Studies, Res. Sq., submitted.","DOI":"10.21203\/rs.3.rs-580991\/v1"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s40249-021-00857-w","article-title":"Tocilizumab treatment for COVID-19 patients: A systematic review and meta-analysis","volume":"10","author":"Wei","year":"2021","journal-title":"Infect. Dis. Poverty"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/rheumatology\/ker311","article-title":"IL-6 inhibition and infection: Treating patients with tocilizumab","volume":"51","author":"Edwards","year":"2011","journal-title":"Rheumatology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1186\/s12879-020-05701-4","article-title":"Effects of Tocilizumab in COVID-19 patients: A cohort study","volume":"20","author":"Vu","year":"2020","journal-title":"BMC Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jointm.2021.07.001","article-title":"COVID-19-Associated Pulmonary Aspergillosis","volume":"1","author":"Dimopoulos","year":"2021","journal-title":"J. Intensive Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1128\/CMR.00055-08","article-title":"Pathogenesis of Apsergillus fumigatus in Invasive Aspergillosis","volume":"22","author":"Dagenais","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_71","first-page":"825","article-title":"Spectrum of Pulmonary Aspergillosis: Histologic, Clinical and Radiologic Findings","volume":"21","author":"Franquet","year":"2001","journal-title":"Radi-Ographics"},{"key":"ref_72","unstructured":"Vuong, F., and Waymack, J.R. (2022, March 12). Aspergillosis. StatPearls. Aspergillosis\u2013StatPearls\u2013NCBI Bookshelf, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK482241\/."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Arastehfar, A., Carvalho, A., Van De Veerdonk, F.L., Jenks, J.D., Koehler, P., Krause, R., Cornely, O.A., Perlin, D.S., Lass-Fl\u00f6rl, C., and Hoenigl, M. (2020). COVID-19 Associated Pulmonary Aspergillosis (CAPA)\u2014From Immunology to Treatment. J. Fungi, 6.","DOI":"10.3390\/jof6020091"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S1473-3099(20)30847-1","article-title":"Defining and managing COVID-19 associated pulmonary aspergillosis: The 2020 ECMM\/ISHAM consensus criteria for research and clinical guidance","volume":"21","author":"Koehler","year":"2021","journal-title":"Lancet Infect."},{"key":"ref_75","first-page":"e7651","article-title":"Radiological Findings in Patients with COVID-19","volume":"12","author":"Fatima","year":"2020","journal-title":"Cureus"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1309\/LM8BW8QNV7NZBROG","article-title":"(1-3)-\u03b2-D-Glucan Assay: A review of its Laboratory and Clinical Application","volume":"42","author":"Bright","year":"2011","journal-title":"Lab. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1128\/AAC.00658-06","article-title":"Reactivity of (1-3)-\u03b2-D-Glucan Assay with Commonly Used Intravenous Antimicrobials","volume":"50","author":"Marty","year":"2006","journal-title":"Antimicrob Agents Chemother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1093\/jac\/dkv419","article-title":"1, 3-\u03b2-d-Glucan contamination of common antimicrobials","volume":"71","author":"Liss","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_79","first-page":"535","article-title":"Assessing the risk of false positive serum galactomannan among patients receiving piperacil-lin\/tazobactam for febrile neutropenia","volume":"55","author":"Demiraslan","year":"2017","journal-title":"Med. Mycol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3109\/00365541003602064","article-title":"False-positive serum and bronchoalveolar lavage Aspergillus galactomannan assays caused by different antibiotics","volume":"42","author":"Boonsarngsuk","year":"2010","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cmi.2020.02.002","article-title":"False positive Aspergillus galactomannan immunoassays associated with intravenous human immunoglobulin administration","volume":"26","author":"Liu","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"747280","DOI":"10.3389\/fphar.2021.747280","article-title":"Investigating Factors of False-Positive Results of Aspergillus Galactomannan Assay: A Case\u2013Control Study in Intensive Care Units","volume":"12","author":"Hung","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1080\/13693780600904918","article-title":"Issues with galactomannan testing","volume":"44","author":"Verweij","year":"2006","journal-title":"Med. Mycol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1128\/CVI.00068-08","article-title":"Development of an Immunochromatographic Lateral-flow device for Rapid Serodiagnosis of Invasive As-pergillosis","volume":"15","author":"Thornton","year":"2008","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Neofytos, D., Railkar, R., Mullane, K.M., Fredricks, D.N., Granwehr, B., Marr, K.A., Almyroudis, N.G., Kontoyiannis, D.P., Maertens, J., and Fox, R. (2015). Correlation between Circulating Fungal Biomarkers and Clinical Outcome in Invasive Aspergillosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129022"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"White, S.K., Schmidt, R.L., Walker, B.S., and E Hanson, K. (2020). (1\u21923)-\u03b2-D-glucan testing for the detection of invasive fungal infections in immunocompromised or critically ill people. Cochrane Database Syst. Rev., 2020.","DOI":"10.1002\/14651858.CD009833.pub2"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"S89","DOI":"10.1093\/cid\/ciaa1786","article-title":"Defining Galactomannan Positivity in the Updated EORTC\/MSGERC Consensus Definitions of Invasive Fungal Diseases","volume":"72","author":"Mercier","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"White, P.L., Price, J.S., Posso, R., Cutlan-Vaughan, M., Vale, L., and Backx, M. (2020). Evaluation of the Performance of the IMMY sona Aspergillus Galactomannan Lateral Flow Assay When Testing Serum to Aid in Diagnosis of Invasive Aspergillosis. J. Clin. Microbiol., 58.","DOI":"10.1128\/JCM.00053-20"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1111\/myc.13352","article-title":"Serum lateral flow assay with digital reader for the diagnosis of invasive pulmonary aspergillosis: A two centre mixed cohort study","volume":"64","author":"Hoenigi","year":"2021","journal-title":"Mycoses"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1007\/s15010-013-0472-5","article-title":"Comparison of a novel Aspergillus lateral-flow device and the Platelia\u00ae galactomannan assay for the diagnosis of invasive aspergillosis following haematopoietic stem cell transplantation","volume":"41","author":"Held","year":"2013","journal-title":"Infection"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1183\/13993003.00583-2015","article-title":"Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management","volume":"47","author":"Denning","year":"2016","journal-title":"Eur. Respir. J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e00095-19","DOI":"10.1128\/JCM.00095-19","article-title":"Evaluation of Aspergillus -Specific Lateral-Flow Device Test Using Serum and Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis","volume":"57","author":"Takazono","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Autier, B., Prattes, J., White, P.L., Valerio, M., Machado, M., Price, J., Egger, M., Gangneux, J.-P., and Hoenigl, M. (2022). Aspergillus Lateral Flow Assay with Digital Reader for the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA): A Multicenter Study. J. Clin. Microbiol., 60.","DOI":"10.1128\/JCM.01689-21"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00134-021-06449-4","article-title":"Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergil-losis","volume":"47","author":"Verweij","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1056\/NEJMoa020191","article-title":"Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis","volume":"347","author":"Herbrecht","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1093\/cid\/cir969","article-title":"Administration of Voriconazole in patients with Renal Dysfunction","volume":"54","author":"Neofytos","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_97","unstructured":"National Institute for Health and Care Excellence (2022, March 14). Voriconazole. VORICONAZOLE | Drug | BNF content published by NICE. Available online: https:\/\/www.nice.org.uk\/bnf-uk-only."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1007\/s00134-021-06471-6","article-title":"Diagnosis and treatment of COVID-19 associated pulmonary aspergillosis in critically ill patients: Results from a European confederation of medical mycology registry","volume":"47","author":"Prattes","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Meijer, E.F.J., Dofferhoff, A.S.M., Hoiting, O., Buil, J.B., and Meis, J.F. (2020). Azole-Resistant COVID-19-Associated Pulmonary Aspergillosis in an Immunocompetent Host: A Case Report. J. Fungi, 6.","DOI":"10.3390\/jof6020079"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Kirchhoff, L. (Mycoses, 2022). COVID-19 associated pulmonary aspergillosis in ICU patients in a German Reference Centre: Phenotypic and Molecular Characterisation of Aspergillus fumigatus isolates, Mycoses, in press.","DOI":"10.1111\/myc.13430"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s13054-021-03753-9","article-title":"Antifungal prophylaxis for prevention of COVID-19-associated pulmonary aspergillosis in critically ill patients: An observational study","volume":"25","author":"Hatzl","year":"2021","journal-title":"Crit. Care"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s13054-021-03728-w","article-title":"Inhaled liposomal amphotericin-B as a prophylactic treatment for COVID-19-associated pulmonary aspergillosis\/aspergillus tracheobronchitis","volume":"25","author":"Rutsaert","year":"2021","journal-title":"Crit. Care"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:38:02Z","timestamp":1760135882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/3228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,17]]},"references-count":102,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23063228"],"URL":"https:\/\/doi.org\/10.3390\/ijms23063228","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,17]]}}}