Epidemiology and Incidence of COVID-19-Associated Pulmonary Aspergillosis (CAPA) in a Greek Tertiary Care Academic Reference Hospital

Abstract
Introduction Invasive pulmonary aspergillosis is an emerging complication among intensive care unit (ICU) patients with COVID-19 (CAPA). In the present study, all CAPA cases during the first year of the pandemic were reviewed in critically ill patients at a 650-bed tertiary Greek COVID-19 reference hospital. Methods Data regarding patients admitted to the ICU of Attikon Hospital in Athens, Greece, between 22 March 2020 and 28 February 2021 with a positive PCR for SARS-CoV-2 infection were reviewed. Clinical and microbiological records were analysed including demographic, clinical, laboratory and radiological features, treatment and outcomes. CAPA was determined according to the recent 2020 ECMM/ISHAM definitions. Results A total of 179 patients were admitted in the ICU and 6 (3.3%) patients were diagnosed with CAPA (4 probable and 2 possible CAPA) with 5/6 with co-infection with multidrug-resistant (MDR) gram-negative pathogens. No patient had a history of immunosuppression. All suffered from acute respiratory distress syndrome. The median (range) time from intubation to diagnosis was 6 (1–14) days. Five patients had positive Aspergillus cultures in bronchial secretions (1 A. fumigatus, 1 A. flavus, 1 A. fumigatus + A. flavus, 1 A. fumigatus + A. terreus and 1 A. terreus) while culture was negative in one patient. All isolates were susceptible to antifungal drugs. Serum galactomannan (GM), pan-Aspergillus PCR and (1,3)-β-d-glucan (BDG) were positive in 4/6 (67%), 5/6 (83%, 3/5 in two consecutive samples) and 4/6 (67%, in consecutive samples) patients, respectively. GM and PCR positive bronchial secretions had GM indices > 9.95 and PCR Ct < 34. All were treated with antifungal drugs with 5 out of 6 receiving isavuconazole. Mortality was 67% (4/6) with 1/4 attributed to CAPA (two died as a result of bacterial septic shock and one as a result of multiorgan failure). Conclusion The incidence of CAPA in ICU patients was 3.3% and it was associated with approximately a 17% attributable mortality in the setting of MDR gram-negative pathogen co-infections.