Invasive Aspergillosis Complicating Severe COVID-19: Cumulative Incidence, Risk Factors, and Outcomes Between the First Wave of the Pandemic and Subsequent Waves, According to the ECMM/ISHAM Classification and a Local Case Assessment

The role of severe COVID-19 as an independent risk factor for invasive aspergillosis remains debated, with reported incidences varying widely across studies. We compared the cumulative incidence, risk factors, and outcomes of invasive pulmonary mold infection (IPMI) in intensive care unit patients with confirmed COVID-19 during the first epidemic wave and subsequent waves up to March 2021 at La Pitié-Salpêtrière Hospital, Paris, France. Patients were systematically screened for fungal infections and classified according to ECMM/ISHAM criteria and a more stringent local assessment. The study included 259 patients (n = 171, first wave and n = 88, subsequent waves). Patient characteristics were similar between periods, although short-course corticosteroid therapy increased over time. Mortality rates remained unchanged. Cumulative incidence of IPMI did not differ significantly between waves, regardless of the classification system used: 12.1% versus 15.1% with ECMM/ISHAM criteria and 4.2% versus 5.8% with local assessment. IPMI was associated with solid organ transplantation and pre-existing long-term corticosteroid therapy, whereas short-course corticosteroid therapy for COVID-19 was not associated with increased risk. IPMI was strongly associated with 90-day mortality. Classification as probable COVID-19-Associated Pulmonary Aspergillosis using the ECMM/ISHAM criteria may be partly influenced by the number of diagnostic samples collected. Overall, our findings underline that the classification system substantially influences both incidence estimates and the interpretation of survival outcomes.