Invasive pulmonary aspergillosis in the COVID‐19 era: An expected new entity

Abstract

Este trabajo describe la aparición de la aspergilosis pulmonar asociada a COVID-19 (CAPA) como una nueva entidad clínica emergente en pacientes críticos con neumonía grave por SARS-CoV-2. Los autores presentan una serie prospectiva de ocho pacientes ingresados en UCI con CAPA diagnosticada entre marzo y mayo de 2020 y la comparan con pacientes colonizados por Aspergillus spp.. Asimismo, se realiza una revisión sistemática de la literatura occidental disponible. La mayoría de los pacientes con CAPA no presentaban inmunosupresión clásica, pero sí síndrome de distrés respiratorio agudo, ventilación mecánica prolongada, tratamiento con corticosteroides y tocilizumab. El diagnóstico fue complejo, con baja sensibilidad de los biomarcadores séricos y hallazgos radiológicos poco específicos. La mortalidad relacionada con CAPA fue del 100% en la serie propia y del 56,3% en la revisión de 96 casos publicados. El estudio subraya que la CAPA es una complicación grave y potencialmente letal de la COVID-19 grave y destaca la necesidad de criterios diagnósticos y terapéuticos consensuados a nivel internacional. Objectives Information on the recently COVID‐19‐associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID‐19), and review the published literature from Western countries.

Methods Prospective study (March to May, 2020) that included all COVID‐19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used.

Results COVID‐19‐associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non‐immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA‐related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all‐cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%.

Conclusions COVID‐19‐associated pulmonary aspergillosis must be considered a serious and potentially life‐threatening complication in patients with severe COVID‐19 receiving immunosuppressive treatment.