Abstract
BackgroundCoronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far.MethodsIn this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria.ResultsWe included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2–9.7) in the MAFP group and 17.5% (95% CI 9.6–31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01–0.63; p = 0.017).ConclusionIn ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19)-associated acute respiratory failure contributes to a highly permissive inflammatory environment
COVID-19-associated pulmonary aspergillosis (CAPA) has been emerging as an important fungal complication of COVID-19 [1], affecting an average of 3.1% [2,3,4,5] of patients hospitalized with COVID-19, 8.9% of patients admitted to the intensive care unit (ICU) [3, 6,7,8,9,10,11], and an average of 20.1% of those requiring invasive ventilation [6, 7, 12,13,14]
All patients included in this study showed an oxygen saturation of less than 88% while breathing ambient air prior to ICU admission and were classified as acute respiratory failure
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19)-associated acute respiratory failure contributes to a highly permissive inflammatory environment. Hatzl et al Crit Care (2021) 25:335 recognition pathways required for the activation of antiviral immunity [1] In this context, COVID-19-associated pulmonary aspergillosis (CAPA) has been emerging as an important fungal complication of COVID-19 [1], affecting an average of 3.1% (range 0.7–7.7%) [2,3,4,5] of patients hospitalized with COVID-19, 8.9% (range 2.5–39%) of patients admitted to the intensive care unit (ICU) [3, 6,7,8,9,10,11], and an average of 20.1% (range 3.2–38%) of those requiring invasive ventilation [6, 7, 12,13,14]. Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far
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