Comparison of Patients With or Without COVID-19 and Without Hematological Diseases Treated for Invasive Pulmonary Aspergillosis: A 5-Year Retrospective Cohort Study with Propensity-Based Adjustment

Abstract

Background: Our aim was to compare epidemiological, clinical and treatment characteristics, and outcomes between patients with diagnoses of coronavirus disease 2019-associated pulmonary aspergillosis (CAPA) or putative invasive pulmonary aspergillosis (PIPA), without hematological cancers.

Methods: Retrospective, monocentric comparative observational cohort study, including nonhematological patients treated for invasive pulmonary aspergillosis between 2018 and 2022. Primary study end points were risk factors for 30-day mortality and clinical failure. To account for the imbalance in antifungal treatment allocation, a propensity score weighting approach was adopted.

Results: A total of 209 patients were included, 93 (44.5%) with CAPA and 116 (55.5%) with PIPA; 144 (68.9%) we admitted to the intensive care unit. Patients with PIPA had higher Charlson Comorbidity Index values (mean [SD], 5.8 [2.6]; range, 0-14) and higher prevalences of chronic obstructive pulmonary disease (30.7%), solid cancer (36.8%), liver cirrhosis (12.3%), and concomitant immunosuppressive therapies (26.1%). Patients with CAPA received more invasive mechanical ventilation (70.5%) and corticosteroids (90.1%), more frequently had positive galactomannan (GM) results with bronchoalveolar lavage (80.5%), and had longer mean hospital stays (62.7 [SD, 52.1; range, 8-276] days) and intensive care unit stays (36 [30.7; 2-168] days). No differences in clinical cure or mortality rates were observed between groups. In multivariable analysis, isavuconazole was the only independent factor for clinical cure, reported also in the propensity score matching analysis (odds ratio, 0.41 [95% confidence interval, .16-1.03]; P = .06). A positive serum GM result was independently associated with 30-day mortality (hazard ratio, 1.78 [95% confidence interval, 1.02-3.10]; P = .04).

Conclusions: Patients with CAPA have fewer comorbid conditions and higher fungal burden than those with PIPA, but clinical outcomes are similar between groups. Isavuconazole was an independent predictor for clinical cure, and serum GM positivity an independent predictor for 30-day mortality.

Keywords: CAPA; COVID-19; aspergillosis; critical care; immunocompromised.

Figure 1.

Kaplan-Meier survival curves after 30 days from the start of therapy of coronavirus disease 2019–associated pulmonary aspergillosis (CAPA) versus putative invasive pulmonary aspergillosis (PIPA) (A) and treatment with isavuconazole versus voriconazole (for patients who did not switch to a second-line regimen) (B).

Figure 2.

Kaplan-Meier curve of occurrence of clinical failure between patients treated only with voriconazole or isavuconazole (without switching to a second-line regimen).