Influenza- and COVID-19-associated pulmonary aspergillosis: are the pictures different?

Abstract

BackgroundInvasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern, in particular for those with acute respiratory distress syndrome (ARDS). As observed previously for influenza-associated ARDS, the SARS-CoV-2 pandemic has shown a high proportion of COVID-19 patients with ARDS to be at risk of developing invasive fungal diseases.MethodsWe used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological and radiological aspects of IAPA and CAPA in a monocentric retrospective study.ResultsAmong the 120 ARDS patients included, we observed equivalent prevalence of IPA in Influenza and COVID-19 populations: 17 IAPA (23.9%) and 10 CAPA (20.4%). There were no significant differences in demographic or admission characteristics between patients with and without IPA. Kaplan-Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA. The duration of mechanical ventilation was higher for IPA patients (23 days [IQR 17–40] than those without (17 days [IQR 9–25], p = 0.038). Patients with COVID-19 and influenza associated ARDS treated with corticosteroids were more likely to develop IPA. Radiological findings of IPA in both populations using the new criteria increased sensitivity but with still poor specificity. Nonetheless, they also showed interesting differences between IAPA and CAPA with a higher proportion of features suggestive of IPA in IAPA patients. Lastly, therapeutic drug monitoring also appeared challenging since a wide proportion of IPA patients had low plasma voriconazole concentrations, with a significant higher delay to reach voriconazole concentrations > 2mg/L in CAPA versus IAPA patients (p = 0.045).ConclusionsICU patients presenting with ARDS during COVID-19 are very similar to those with severe influenza pneumonia in terms of prevalence of IPA and outcome, while CAPA is mainly favored by advanced age irrespective of the background. The dramatic consequences on the patients' prognosis emphasize the need for a better awareness in these particular populations. Larger prospective studies may help in designing the most well-adapted personalized management to prevent IPA, which represents a high burden of death in severe COVID-19 and Influenza pneumonia.