Invasive pulmonary aspergillosis among ICU patients with COVID-19, influenza, and preexisting host factors: a nationwide cohort study

BACKGROUND: Previous studies on the association between coronavirus disease 2019 (COVID-19) and invasive pulmonary aspergillosis (IPA) were limited by their single-center nature and small patient population. Whether aspergillosis risk is related to COVID-19 or other factors remains unclear. This study aimed to determine whether COVID-19 among intensive care unit (ICU) patients is associated with an increased incidence of IPA compared with that among individuals with influenza or preexisting host factors (control). METHODS: This was a nationwide study performed using the Korean National Health Insurance Service database. A cohort of 28,089 patients with COVID-19 (2020-2022), 9993 individuals with influenza (2015-2019), and 11,807 control patients (2015-2019) were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) of outcomes were calculated between the propensity score-matched groups. RESULTS: After matching, patients with COVID-19 were paired with 9649 patients with influenza (mean [SD] age, 72.7 [15.1] years vs. 72.7 [14.5] years; men, 53.3% vs. 52.2%) and 5709 control patients (mean [SD] age, 71.8 [12.0] years vs. 72.2 [11.1] years; men, 70.0% vs. 72.2%). The COVID-19 group was not associated with an increased risk of IPA compared to the observations in the influenza (OR, 1.20; 95% CI 0.97-1.48) or the control (OR, 1.06; 95% CI 0.89-1.26) group. Consistent findings were observed for patients receiving high-flow nasal cannula or mechanical ventilation. The risk factors for IPA included male sex, chronic pulmonary disease, chronic liver disease, admission to higher-volume hospitals, renal replacement therapy, and length of hospital stay; COVID-19 was not implicated (COVID-19 vs. influenza; adjusted OR, 1.22; 95% CI 0.97-1.54 and COVID-19 vs. control; adjusted OR, 1.17; 95% CI 0.97-1.42). In the COVID-19 group, corticosteroid use for ≥ 7 days was associated with an increased risk of IPA, regardless of the dosage. CONCLUSIONS: ICU patients with COVID-19 were not at an increased risk of IPA compared to those with influenza or preexisting host factors. COVID-19 may not predispose to IPA.