{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:17:45Z","timestamp":1782951465231,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"crossref"}]},{"name":"PTE Federal","award":["6 NU3HCK000007-01-01"],"award-info":[{"award-number":["6 NU3HCK000007-01-01"]}]},{"name":"PTE Federal","award":["60060796 AKU"],"award-info":[{"award-number":["60060796 AKU"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Invasive fungal infections (IFIs) in patients with COVID-19 contribute to significant morbidity and mortality, with reported incidence between 5% and 26.7%. COVID-19-associated pulmonary aspergillosis (CAPA), candidiasis (CAC), mucormycosis (CAM), and Pneumocystis jirovecii pneumonia (PJP) are the most common IFIs in this population. Methodology: We conducted a case\u2013control study in the ratio of 1:2 between March 2020 and April 2022 using institutional COVID-19 registry data. The cases were severe COVID-19 patients with IFIs, and the controls were severe COVID-19 patients without IFIs. Multivariate logistic regression was used to identify independent risk factors, with adjusted odds ratios (aOR) and 95% confidence intervals (CIs). The outcomes for the study were to assess the clinical outcomes, i.e., in-hospital mortality and length of hospitalization in a subgroup of severe COVID-19 patients who had IFIs. A p-value &lt; 0.05 was considered significant. Results: Among 5368 COVID-19 patients admitted to hospital during the study period, 1333 had a severe infection. Of these, 158\/1333 (11.8%) met the criteria for IFIs, with a median age of 65 years and 71% male predominance. Diabetes (53.8%) and hypertension (57.6%) were the most common comorbid conditions. Acute respiratory distress syndrome (ARDS) developed in 55% of patients. Overall mortality was 48%. For the case control analysis, 119 patients with IFIs were selected as cases and 240 patients without IFIs were selected as controls. On univariate analysis ARDS was significantly associated with IFIs (OR: 1.91; 95% CI: 1.23\u20132.99, p-value = 0.004). Patients with IFIs had higher odds of being on hemodialysis compared to those without IFIs (OR: 2.17; 95% CI: 1.18\u20133.99; p-value = 0.013). Mechanical ventilation was found to be independently associated with IFIs in multivariate logistic regression analysis (OR: 2.5, 95% CI: 1.58\u20133.96, p-value &lt; 0.001). The odds for in-hospital death in patients with IFIs were 2.19 (95% CI: 1.35\u20133.56; p-value &lt; 0.001) compared to patients without IFIs. The median hospital stay for patients with IFIs was markedly longer (14 days) compared to 8 days in patients without IFIs. Conclusions: IFIs significantly worsened outcomes in severe COVID-19 patients, leading to increased mortality and prolonged hospital stays. Mechanical ventilation was an independent risk factor for IFIs.<\/jats:p>","DOI":"10.3390\/pathogens14101064","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:17:35Z","timestamp":1761056255000},"page":"1064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Risk Factors and Clinical Outcomes of Invasive Fungal Infections in Patients with Severe COVID-19: A Case\u2013Control Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Nosheen","family":"Nasir","sequence":"first","affiliation":[{"name":"Department of Medicine, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9919-0873","authenticated-orcid":false,"given":"Syed Abbas Moazzam","family":"Kazmi","sequence":"additional","affiliation":[{"name":"Medical College, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9921-4660","authenticated-orcid":false,"given":"Joveria","family":"Farooqi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5796-2548","authenticated-orcid":false,"given":"Muhammad","family":"Irfan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2497-7847","authenticated-orcid":false,"given":"Kauser","family":"Jabeen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rovina, N., Koukaki, E., Romanou, V., Ampelioti, S., Loverdos, K., Chantziara, V., Koutsoukou, A., and Dimopoulos, G. (2022). Fungal Infections in Critically Ill COVID-19 Patients: Inevitabile Malum. J. Clin. Med., 11.","DOI":"10.3390\/jcm11072017"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s12281-022-00434-0","article-title":"Overview of COVID-19-Associated Invasive Fungal Infection","volume":"16","author":"Shishido","year":"2022","journal-title":"Curr. Fungal Infect. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Raffaelli, F., Tanzarella, E.S., De Pascale, G., and Tumbarello, M. (2022). Invasive Respiratory Fungal Infections in COVID-19 Critically Ill Patients. J. Fungi, 8.","DOI":"10.3390\/jof8040415"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101198","DOI":"10.1016\/j.mycmed.2021.101198","article-title":"Invasive Fungal Infections among Critically Ill Adult COVID-19 Patients: First Experiences from the National Centre in Hungary","volume":"31","author":"Szabo","year":"2021","journal-title":"J. Med. Mycol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1111\/myc.13135","article-title":"COVID-19-Associated Pulmonary Aspergillosis (CAPA) in Patients Admitted with Severe COVID-19 Pneumonia: An Observational Study from Pakistan","volume":"63","author":"Nasir","year":"2020","journal-title":"Mycoses"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"John, T.M., Jacob, C.N., and Kontoyiannis, D.P. (2021). When Uncontrolled Diabetes Mellitus and Severe COVID-19 Converge: The Perfect Storm for Mucormycosis. J. Fungi, 7.","DOI":"10.3390\/jof7040298"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1111\/myc.13338","article-title":"COVID-19-Associated Mucormycosis: An Updated Systematic Review of Literature","volume":"64","author":"Pal","year":"2021","journal-title":"Mycoses"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e1083","DOI":"10.1002\/hsr2.1083","article-title":"ur Frequency and Survival of COVID Associated Mucormycosis Patients at Tertiary Care Hospitals in Pakistan: A Retrospective Observational Study","volume":"6","author":"Irfan","year":"2023","journal-title":"Health Sci. Rep."},{"key":"ref_10","unstructured":"World Health Organization (2023). Clinical Management of COVID-19: Living Guideline, World Health Organization."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e149","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. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Arastehfar, A., Carvalho, A., Nguyen, M.H., Hedayati, M.T., Netea, M.G., Perlin, D.S., and Hoenigl, M. (2020). COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?. J. Fungi, 6.","DOI":"10.3390\/jof6040211"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1111\/myc.13335","article-title":"ECMM and ISHAM ECMM\/ISHAM Recommendations for Clinical Management of COVID-19 Associated Mucormycosis in Low- and Middle-Income Countries","volume":"64","author":"Rudramurthy","year":"2021","journal-title":"Mycoses"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1016\/S1473-3099(19)30312-3","article-title":"Global Guideline for the Diagnosis and Management of Mucormycosis: An Initiative of the European Confederation of Medical Mycology in Cooperation with the Mycoses Study Group Education and Research Consortium","volume":"19","author":"Cornely","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s41564-022-01172-2","article-title":"COVID-19-Associated Fungal Infections","volume":"7","author":"Hoenigl","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ioannou, P., Kofteridis, D.P., Alexakis, K., Koutserimpas, C., Papakitsou, I., Maraki, S., and Samonis, G. (2022). Candida Species Isolation from Hospitalized Patients with COVID-19-A Retrospective Study. Diagnostics, 12.","DOI":"10.3390\/diagnostics12123065"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hussain, S., Riad, A., Singh, A., Klugarov\u00e1, J., Antony, B., Banna, H., and Klugar, M. (2021). Global Prevalence of COVID-19-Associated Mucormycosis (CAM): Living Systematic Review and Meta-Analysis. J. Fungi, 7.","DOI":"10.3390\/jof7110985"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00725","DOI":"10.1002\/rcr2.725","article-title":"The Diagnostic Challenge of Pneumocystis Pneumonia and COVID-19 Co-Infection in HIV","volume":"9","author":"Broadhurst","year":"2021","journal-title":"Respirol. Case Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Roman-Montes, C.M., Bojorges-Aguilar, S., Correl-Herrera, E.A., Rangel-Cordero, A., D\u00edaz-Lomel\u00ed, P., Cervantes-Sanchez, A., Martinez-Guerra, B.A., Rajme-L\u00f3pez, S., Tamez Torres, K.M., and Mart\u00ednez-Gamboa, R.A. (2023). Fungal Infections in the ICU during the COVID-19 Pandemic in Mexico. J. Fungi, 9.","DOI":"10.3390\/jof9050583"},{"key":"ref_20","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":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jhin.2021.04.012","article-title":"Incidence, Diagnosis and Outcomes of COVID-19-Associated Pulmonary Aspergillosis (CAPA): A Systematic Review","volume":"113","author":"Chong","year":"2021","journal-title":"J. Hosp. Infect."},{"key":"ref_22","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":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.cmi.2023.03.008","article-title":"COVID-19\u2013Associated Mucormycosis: A Systematic Review and Meta-Analysis of 958 Cases","volume":"29","author":"Manay","year":"2023","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1111\/myc.13334","article-title":"Mucormycosis in Patients with COVID-19: A Cross-sectional Descriptive Multicentre Study from Iran","volume":"64","author":"Pakdel","year":"2021","journal-title":"Mycoses"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cattaneo, L., Buonomo, A.R., Iacovazzo, C., Giaccone, A., Scotto, R., Viceconte, G., Mercinelli, S., Vargas, M., Roscetto, E., and Cacciatore, F. (2023). Invasive Fungal Infections in Hospitalized Patients with COVID-19: A Non-Intensive Care Single-Centre Experience during the First Pandemic Waves. J. Fungi, 9.","DOI":"10.3390\/jof9010086"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11046-025-00928-8","article-title":"Epidemiology of Coronavirus Disease 2019-Associated Fungal Infections in the Intensive Care Unit: A Single-Center Retrospective Study","volume":"190","author":"Little","year":"2025","journal-title":"Mycopathologia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"ofae108","DOI":"10.1093\/ofid\/ofae108","article-title":"Incidence and Mortality of COVID-19 Associated Invasive Fungal Infections Among Critically-Ill Intubated Patients: A Multicenter Retrospective Cohort Analysis","volume":"11","author":"Papadopoulos","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"ofae012","DOI":"10.1093\/ofid\/ofae012","article-title":"Increased Risk of Invasive Aspergillosis in Immunocompromised Patients With Persistent SARS-CoV-2 Viral Shedding >8 Weeks, Retrospective Case-Control Study","volume":"11","author":"Melenotte","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1016\/j.cmi.2021.07.038","article-title":"COVID-19 Associated Mucormycosis: A Life-Threatening Complication in Patients Admitted with Severe to Critical COVID-19 from Pakistan","volume":"27","author":"Nasir","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/myc.13529","article-title":"Comparison of Risk Factors and Outcome of Patients with and without COVID-19-Associated Pulmonary Aspergillosis from Pakistan: A Case\u2013Control Study","volume":"66","author":"Nasir","year":"2023","journal-title":"Mycoses"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jinf.2023.02.014","article-title":"Rising Incidence of Pneumocystis Pneumonia: A Population-Level Descriptive Ecological Study in England","volume":"86","author":"Pates","year":"2023","journal-title":"J. Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"ofad043","DOI":"10.1093\/ofid\/ofad043","article-title":"Pneumocystis Jirovecii Infections Among COVID-19 Patients: A Case Series and Literature Review","volume":"10","author":"Amstutz","year":"2023","journal-title":"Open Forum Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Chen, H., Yu, L., Wang, L., Zhang, J., Yan, X., and Jiang, Y. (2024). Demographic Characteristics and Risk Factors for Invasive Fungal Sinusitis in the Context of COVID-19: A Systematic Review and Meta-Analysis. Int. J. Infect. Dis. IJID  Off. Publ. Int. Soc. Infect. Dis., 144.","DOI":"10.1016\/j.ijid.2024.107054"},{"key":"ref_34","first-page":"20499361221097417","article-title":"Unnecessary Use of Corticosteroids for Managing Early Mild Symptoms of COVID-19 May Lead to Rhino-Ortibal-Cerebral Mucormycosis in Patients with Diabetes\u2014A Case Series from Lahore, Pakistan","volume":"9","author":"Iqtadar","year":"2022","journal-title":"Ther. Adv. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"639","DOI":"10.29271\/jcpsp.2022.05.639","article-title":"Aspergillosis and Mucormycosis in COVID-19 Patients: A Systematic Review","volume":"32","author":"Afzal","year":"2022","journal-title":"J. Coll. Physicians Surg. Pak."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ezeokoli, O.T., Gcilitshana, O., and Pohl, C.H. (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_37","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.4103\/jfmpc.jfmpc_1130_23","article-title":"Coronavirus Disease (COVID-19)-Associated Mucormycosis (CAM): The Unholy Triad of COVID-19, Diabetes Mellitus, and Corticosteroid Therapy","volume":"12","author":"Juyal","year":"2023","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3000605211043413","DOI":"10.1177\/03000605211043413","article-title":"Predisposing Factors of Important Invasive Fungal Coinfections in COVID-19 Patients: A Review Article\u2014Mohammadali Zia, Mohammad Goli, 2021","volume":"49","author":"Zia","year":"2021","journal-title":"J. Int. Med. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.cmi.2020.12.030","article-title":"Outbreak of Candida Auris Infection in a COVID-19 Hospital in Mexico","volume":"27","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"100127","DOI":"10.1016\/j.clinpr.2021.100127","article-title":"SARS-CoV-2 Related ARDS and Invasive Fungal Infections in Intensive Care Patients","volume":"13","author":"Borg","year":"2022","journal-title":"Clin. Infect. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Maeshima, K., Yamamoto, R., Matsumura, K., Kaito, D., Homma, K., Yamakawa, K., Tagami, T., Hayakawa, M., Ogura, T., and Hirayama, A. (2024). Fungal Infection-Related Conditions and Outcomes in Severe COVID-19: A Nationwide Case-Control Study. BMC Infect. Dis., 24.","DOI":"10.1186\/s12879-024-10317-z"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e543","DOI":"10.1016\/S2666-5247(21)00237-8","article-title":"The Emergence of COVID-19 Associated Mucormycosis: A Review of Cases from 18 Countries","volume":"3","author":"Hoenigl","year":"2022","journal-title":"Lancet Microbe"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1111\/myc.13332","article-title":"Characteristics of Candidemia in COVID-19 Patients; Increased Incidence, Earlier Occurrence and Higher Mortality Rates Compared to non-COVID-19 Patients","volume":"64","author":"Kayaaslan","year":"2021","journal-title":"Mycoses"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/myc.13369","article-title":"COVID-19-associated Subacute Invasive Pulmonary Aspergillosis","volume":"65","author":"Swain","year":"2022","journal-title":"Mycoses"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Than, H.M., Dao, T.V., Cao, T.V., Duong, T.V., Pham, T.N., Nguyen, C.T., Vu, P.D., Le, N.V., Do, B.N., and Nguyen, P.V. (2025). Factors Associated with Prolonged Mechanical Ventilation and 30-Day Mortality in Intubated COVID-19 Patients with Invasive Fungal Infections: A Retrospective Observational Study. Trop. Med. Infect. Dis., 10.","DOI":"10.3390\/tropicalmed10050124"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/1064\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T04:19:34Z","timestamp":1761193174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/1064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pathogens14101064"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14101064","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]}}}