COVID‐19–associated pulmonary aspergillosis: a prospective single‐center dual case series

Abstract

Background COVID‐19–associated pulmonary aspergillosis (CAPA) has emerged as an invasive fungal disease, often affecting previously immunocompetent, mechanically ventilated, intensive care unit (ICU) patients. Incidence rates of 3.8%–33.3% have been reported depending on the geographic area, with high (47%) mortality. Objectives Here, we describe a single‐centre prospective case series with CAPA cases from both the first (March‐May, n = 5/33) and second (mid‐September through mid‐December, n = 8/33) COVID‐19 wave at a 500‐bed teaching hospital in the Netherlands. Patients/Methods In the first COVID‐19 wave, a total of 265 SARS‐CoV‐2 PCR‐positive patients were admitted to our hospital of whom 33 needed intubation and mechanical ventilation. In the second wave, 508 SARS‐CoV‐2 PCR‐positive patients were admitted of whom 33 needed mechanical ventilation. Data were prospectively collected. Results We found a significant decrease in COVID‐19 patients needing mechanical ventilation in the ICU in the second wave (p < .01). From these patients, however, a higher percentage were diagnosed with CAPA (24.2% vs 15.2%), although not significant (p = .36). All CAPA patients encountered in the second wave received dexamethasone. Mortality between both groups was similarly high (40%–50%). Moreover, we found environmental TR34/L98H azole‐resistant Aspergillus fumigatus isolates in two separate patients. Conclusions In this series, 19.7% (n = 13/66) of mechanically ventilated SARS‐CoV‐2 patients were diagnosed with CAPA. In addition, we found a significant reduction in COVID‐19 patients needing mechanical ventilation on the ICU in the second wave. Numbers are too small to determine whether there is a true difference in CAPA incidence in mechanically ventilated patients between the two waves, and whether it could be attributed to dexamethasone SARS‐CoV‐2 therapy.

Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis

“…BDG 1/? [ 22 ] France 19 Culture 7/9 GM 7/9 PCR – A. fumigatus (14), A. calidoustus (1), A. niger (1) Culture 9/10 GM– PCR – GM 1/12 BDG – [ 23 ] Pakistan 5 Not specified A. fumigatus (1), A. flavus (4), A. niger (1) Not specified GM 0/5 BDG 1/5 [ 24 ] USA 4 Not specified A. fumigatus (4) Not specified GM 1/3 BDG – [ 25 ] France 7 Culture not specified/5 GM 3/5 PCR 2/5 A. fumigatus (5) Not specified GM 1/7 BDG 2/7 [ 26 ] Netherlands 8 Culture 7/7 GM 2/6 PCR 4/5 A. fumigatus (7) Culture 1/1 GM 1/1 PCR 1/1 GM 0/1 [ 27 ] Netherlands 11 Culture 5/40 GM 11/37 PCR 11/40 A. fumigatus (3) Culture 3/47 GM not performed PCR 23/30 GM 0/11 [ 28 ] USA …”

“…The performance of LFD tests has been studied in ICU patients [ 30 ], showing a good overall test performance (sensitivity 0.88–0.94, specificity 0.81, and the area under the ROC curve 0.90–0.94) [ 30 ]. AspLFD (OLM Diagnostics) was used in 8 CAPA cases using one TA and seven BAL samples [ 27 ]. The AspLFD was positive in six patients but did not correspond with GM detection in four.…”

“…Azole resistance Five cases of azole-resistant CAPA have been reported [ 27 , 38 , 39 , 44 ]. In four cases the TR 34 /L98H resistance mutation was detected and in one case a TR 46 /Y121F/T289A mutation, which are associated with environmental resistance selection.…”

Incidence, Risk Factors, and Outcomes of Patients with COVID‑19‑Associated Pulmonary Aspergillosis (CAPA) in Intensive Care Units: A Systematic Review and Meta-Analysis Of 29 Cohort Studies

“…Meijer and others conducted a small-sample cohort study (66 ICU patients with COVID-19) and found that the incidence of CAPA was 19.7% (n = 13/66), and the fatality rate of a single study was 46.2% (6/13); the author's team listed some of the articles that have been published and analysed for the CAPA fatality rate. The pooled CFR for CAPA was 47% (62/132) [32].…”

“…Of the 29 studies, (27.59%) were from France [2,13,[21][22][23][24][25][26]], 4 (13.79%) were from the United Kingdom (UK) [27][28][29][30][31][32], 4 (13.79%) were from the Netherlands [33,34], 2 (6.90%) were from Germany [35,36], 2 (6.90%) were from Spain [15,37], 2 (6.90%) were from Switzerland [14,38], 1 (3.45%) was from the USA [39], 1 (3.45%) was from Belgium [40], 1 (3.45%) was from China[6], 1(3.45%) was from Pakistan [41], 1(3.45%) was from Denmark [42], 1 (3.45%) was from Italy [43] and 1(3.45%) from Mexico [44]. Twelve studies dealt with patients who received mechanical ventilation, eight studies were of patients with ARDS, one study was on extracorporeal membrane oxygenation (ECMO), 1 study looked at acute respiratory failure (ARF), and seven studies included other patients with severe COVID-19 (See additional le 1, supplementary 1).…”