J Korean Med Sci.  2022 May;37(18):e134. 10.3346/jkms.2022.37.e134.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study

• Kim SH
• Hong JY
• Bae S
• Lee H
• Wi YM
• Ko JH
• Kim B
• Joo EJ
• Seok H
• Shi HJ
• Yoo JR
• Hyun M
• Kim Ha
• Jang S
• Mun SJ
• Kim J
• Kim MC
• Jung DS
• Kim SH
• Peck KR

• KMID: 2529708
• DOI: http://doi.org/10.3346/jkms.2022.37.e134

Abstract

Background
Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated.
Methods
This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model.
Results
Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089).
Conclusion
Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

Keyword

Aspergillosis; COVID-19; SARS-CoV-2; Steroid

Figure

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  Fig. 1 Study population.COVID-19 = coronavirus disease 2019, CAPA = COVID-19-associated pulmonary aspergillosis.

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  Fig. 2 Cumulative incidence curve of primary and secondary outcomes. (A) 90-day overall mortality (raw data), (B) 90-day overall mortality (propensity score [PS]-matched model), (C) respiratory support-free rates among surviving patients (raw data), and (D) respiratory support-free rates among surviving patients (PS-matched model).CAPA = COVID-19-associated pulmonary aspergillosis.

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