COVID-19-associated pulmonary aspergillosis (CAPA) in hematological patients: Could antifungal prophylaxis be necessary? A nationwide study

COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. COVID-19 was diagnosed in 3.85% (4,367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1% vs. 3%; p<0.001). Candida spp. showed higher rate in non-COVID-19 (74.2% vs. 66.8%; p=0.015), meanwhile Aspergillus spp. confirmed its predominance in COVID-19 hematological patients (35.4% vs. 19.1%; p<0.001). IPA was diagnosed in 703 patients and 11.2% (79 cases) were CAPA. The multivariate logistic regression analysis found that the diagnosis of COVID-19 disease at hospital admission increased more than two-fold IPA development [OR: 2.5, 95CI (1.9-3.1), p<0.001]. B-cell malignancies – specifically B-cell non-Hodgkin lymphoma, multiple myeloma, chronic lymphocytic leukemia and acute lymphoblastic leukemia – showed between four- and six-fold higher CAPA development and 90-day mortality rates ranging between 50% and 72%. However, myeloid malignancies did not show higher CAPA rates compared to IPA in non-COVID-19 patients. COVID-19 constitutes an independent risk factor for developing aspergillosis in B-cell hematological malignancies and the use of antifungal prophylaxis during hospitalizations may be warranted.