COVID-associated pulmonary aspergillosis in the United States: Is it rare or have we missed the diagnosis?

While gillosis the (CAPA) incidence in COVID-19 of coronavirus patients disease admitted (COVID)-associated to the intensive pulmonary care unit (ICU) asper- in Europe is widely published (incidence up to 30%) (1), data on CAPA from the United States is lacking or has not been well described (2, 3). During the first surge of COVID-19 (March to August 2020), members of the Fungal Diagnostic Laboratories Consortium (FDLC) were formally asked if they had recovered Aspergillus species in respiratory specimens from patients with confirmed COVID-19 after ICU admission (4). Only 8 of the 23 FDLC member laboratory sites (35%) responded in the affirmative. Cumulatively, data from 33 patients who were admitted to the ICU and/or intubated in the ICU setting were identified at four academic medical centers (among a total of 1,633 ICU patients) and were collected and summarized (Table 1). The overall incidence was 2%. Based on the most recent CAPA case definition (3, 5), 17 cases were considered to be possible CAPA, and 16 cases were determined to be probable CAPA. The mean age was 63.2 (range, 38 to 85), 55% were male, 42% were white, and 58% had hypertension. Only 9 (27%) patients were immunosuppressed at the time of COVID-19 diagnosis, but 16 (48%) patients received immunosuppression therapy during COVID-19 treatment. Overall, 20 cases (61%) were treated with antifungals (75% in probable CAPA, 47% in possible CAPA). Mortality was 67% overall (75% in probable CAPA cases; 59% in possible CAPA cases). The median time of first isolation of Aspergillus spp. from respiratory tract specimens was 13 days after ICU admission (range, 0 to 35 days). A. fumigatus was the most common species (79%), followed by A. Niger (15%), A. flavus (3%), and A. parasiticus (3%). These Aspergillus spp. were initially recovered from the following sources: endotracheal tube aspirate (61%), tracheal aspirate (12%), sputum (21%), and bronchoalveolar lavage (BAL) fluid (21%). Testing for serum galactomannan (GM) (Platelia EIA, Bio-Rad) was performed in 23 cases (70%). Only four cases (17%) tested positive, yielding a positive rate of 28.6% (4/14) for probable CAPA. This is consistent with other published reports (6, 7). Only 7 cases (21%) had BAL samples collected, of which BAL GM was not even ordered in 4 cases (57%), and of the 3 cases that underwent BAL GM testing, two were positive (GM index 6.16, 3.52). Serum 1,3-beta-D-glucan (BDG) (Fungitell, Associated of Cape Cod, Inc.) testing was available for 23 cases (70%); 8 (35%) were positive, yielding a positive rate of 50% (7/14) for probable CAPA cases.