Effects of antifungal treatment in COVID-19-associated pulmonary aspergillosis: A European multicenter cohort study.

Abstract

The management of COVID-19-associated invasive aspergillosis (CAPA) is still debated while cases continue to occur, and more and more frequently in vulnerable populations, stressing the importance of obtaining data on the treatment of this disease. Only small cohort studies and case-reports have yet discussed this essential issue and data obtained are insufficient to conclude with confidence. Is antifungal treatment associated with lower 60-day mortality in patients with probable or proven CAPA? We assessed the association of antifungal treatment with 60-day mortality for probable/proven CAPA cases from a French multicenter study and all consecutive CAPA cases (post-2020) from intensive care units of five major European centers. Patients were compared according to antifungal treatment. Survival analysis was conducted using Cox regression analysis and inverse probability of treatment weighting based on a propensity score. In total, 259 CAPA patients were included, 237 (91.5%) receiving antifungals for CAPA of whom 215 (90.7%) received azole antifungal drugs. Baseline characteristics were similar between patients who received antifungals and those who did not. Age (HR 1.02, 95%CI:1.00-1.04, p=0.048), immunosuppressive treatment (HR 2.08, 95%CI:1.12-3.41, p<0.001], and remdesivir administration (HR 1.96, 95%CI:1.12-3.41, p=0.018) were independently associated with increased 60-day mortality by Cox regression analysis in the raw population. Male sex (HR 0.61, 95%CI:0.40-0.95, p=0.024) and antifungal treatment (HR 0.31, 95%CI:0.17-0.59, p<0.001) were associated with lower 60-day mortality. Cox-weighted regression showed lower 60-day mortality for patients receiving antifungals (weighted HR 0.28 [95%CI:0.13-0.58], p<0.001. We observed that antifungal treatment was associated with lower 60-day mortality in CAPA patients. The high mortality rate observed in CAPA in immunocompromised patients and improved outcome for treated patients should encourage clinicians to actively screen for CAPA to enable rapid diagnosis and targeted treatment.