Antifungal Prophylaxis and Preemptive Therapy to Prevent COVID-19-Associated Pulmonary Aspergillosis in Patients Requiring Advanced Respiratory Support: A Real-World Cohort Study in China.

OBJECTIVES: COVID-19-associated pulmonary aspergillosis (CAPA) is a frequent and life-threatening complication in critically ill patients. However, the role of antifungal prophylaxis and preemptive therapy remains unclear. This study aimed to evaluate the effects and safety of these strategies. METHODS: This single-center, retrospective study included patients with COVID-19 who required advanced respiratory support (high-flow nasal cannula, non-rebreathing mask, mechanical ventilation, or extracorporeal membrane oxygenation) between November 2022 and December 2023. The primary outcome was the incidence of CAPA. The secondary outcome was all-cause in-hospital mortality. Safety outcomes included clinical adverse events and laboratory abnormalities. RESULTS: Of the 267 patients included, 26 received antifungal prophylaxis, and 21 received preemptive therapy. The incidence of CAPA in the non-prevention group (22.7%) was higher than in the prophylactic (3.8%, P = 0.02) and preemptive (4.8%, P = 0.05) groups. Antifungal prophylaxis was independently associated with a reduced risk of CAPA versus non-prevention (sub-distribution hazard ratio 0.11, 95% CI 0.01-0.92, P = 0.04). In-hospital mortality did not differ significantly among the three groups, with rates of 46.2%, 52.4%, and 44.1% in the prophylactic, preemptive, and non-prevention groups, respectively (P = 0.76). Adverse events were comparable overall, with only five adverse drug reactions (Grade 1) reported. CONCLUSIONS: In patients with COVID-19 requiring advanced respiratory support, antifungal prophylaxis was associated with a significantly reduced incidence of CAPA, and preemptive therapy also showed a reducing trend. Both strategies demonstrated favorable safety profiles, whereas neither improved survival. Further studies are warranted to investigate the clinical utility of these strategies.