Objectives
Coronavirus disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome.
Methods
The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centers from nine different countries to assess epidemiology, risk factors, and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions.
Results
A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) patients with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0-31) after ICU admission predominantly in older patients [adjusted hazard ratio (aHR) 1.04 per year; 95%CI 1.02-1.06] with any form of invasive respiratory support (HR 3.4; 95%CI 1.84-6.25) and receiving tocilizumab (HR 2.45; 95%CI 1.41-4.25). Median prevalence of CAPA per center was 10.7% (range 1.7%-26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel-Byar
p<0.001
) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR=2.14; 95%CI: 1.59-2.87,
p<=0.001
).
Conclusion
Prevalence of CAPA varied between centers. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.
Background
Coronavirus 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.
Methods
In 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.
Results
We 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).
Conclusion
In 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.
Dear Editor,Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) has emerged as an important complication among patients with acute respiratory failure caused by SARS-CoV-2 [1-3]. A cornerstone in CAPA diagnosis is microbiology, including culture from lower respiratory tract samples, and bronchoalveolar lavage fluid (BALF) galactomannan (GM) [4,5].We performed a multinational cohort study including 20 centers in 9 countries with the aim to evaluate diagnostic approaches and treatment of CAPA as well as CAPA prevalence. All participating centers were invited to provide data on diagnostic work-up, treatment and outcome on prospective cohorts of consecutive COVID-19 ICU patients (inclusion criteria: SARS-CoV-2-positive polymerase chain reaction, admission to intensive care unit (ICU) due to respiratory failure) with and without CAPA via an online case report form between 03/2020 and 05/2021. Cases were then classified according to the 2020 ECMM/ISHAM consensus criteria [4]. The study protocol was approved by the Medical University of
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