Corticosteroids As Risk Factor for COVID-19-associated Pulmonary Aspergillosis in Intensive Care Patients

Purpose: Corticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA.

Methods: We performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charité Universitätsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA.

Results: Altogether, among the n = 522 intensive care patients analyzed, n = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p < 0.001) and higher levels of IL-6 (1,005 vs. 461, p < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p = 0.024), renal replacement therapy (60% vs. 41%, p = 0.024), and they were more likely to die (64% vs. 48%, p = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112-8.697) and SAPS (OR 1.063, CI95 1.028-1.098) to be independent risk factors for CAPA.

Conclusion: In our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA.

Trial Registration: Registration number DRKS00024578, Date of registration March 3rd, 2021.