A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

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Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe COVID-19, similarly to influenza; yet the clinical invasiveness is more debated. We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 intensive care unit (ICU) fatalities in a tertiary care center. In this monocentric, descriptive, retrospective case series we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure that underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the ICM-IAPA and ECMM/ISHAM-CAPA consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as missed-diagnosis upon autopsy in 8% of proven cases (n=1/12), yet most frequently found as confirmation of probable antemortem diagnosis (n=11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n=3) and COVID-19 (n=3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case-fatalities. Our findings highlight an important need for VAPA awareness with an emphasis on mycological bronchoscopic work-up. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).