COVID-19-Associated Invasive Pulmonary Aspergillosis in the Intensive Care Unit: A Case Series in a Portuguese Hospital.

David Ranhel,Maria Pessanha,Raquel Sabino,Judite Batista,Luís Coelho,Elisabete Cristovam,Cristina Toscano,Ana Ribeiro,Filipa Monteiro,Ana Dias,Pedro Freire,Cristina Veríssimo,Ana Duarte

doi:10.3390/jof7100881

Abstract

Invasive pulmonary aspergillosis (IPA) has become a recognizable complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs). Alveolar damage in the context of acute respiratory distress syndrome (ARDS) appears to be the culprit in facilitating fungal invasion in COVID-19 patients, leading to a COVID-19-associated pulmonary aspergillosis (CAPA) phenomenon. From November 2020 to 15 February 2021, 248 COVID-19 patients were admitted to our ICUs, of whom ten patients (4% incidence) were classified as either probable (six) or possible (four) CAPA cases. Seven patients had positive cultural results: Aspergillus fumigatus sensu stricto (five), A. terreus sensu stricto (one), and A. welwitschiae (one). Five patients had positive bronchoalveolar lavage (BAL) and galactomannan (GM), and two patients had both positive cultural and GM criteria. All but two patients received voriconazole. Mortality rate was 30%. Strict interpretation of classic IPA definition would have resulted in eight overlooked CAPA cases. Broader diagnostic criteria are essential in this context, even though differentiation between Aspergillus colonization and invasive disease might be more challenging. Herein, we aim to raise awareness of CAPA in view of its potential detrimental outcome, emphasizing the relevance of a low threshold for screening and early antifungal treatment in ARDS patients.

Highlights

Invasive pulmonary aspergillosis (IPA) is a well-defined issue in immunocompromised patients, especially in relation to hematologic malignancies and transplantation
bronchoalveolar lavage (BAL) samples were plated on Sabouraud dextrose agar (30 ◦C; aerobiosis) and the incubation periods were longer, with a 72 h window for standard media, and 120 h window for Sabouraud dextrose agar
A total of 248 patients were admitted to our intensive care units (ICUs) with COVID-19 in the aforementioned period, from whom resulted the presently described case series of 10 patients with mild to moderate Acute respiratory distress syndrome (ARDS) and suspected diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA) (4% incidence) (Table 1)

Summary

Introduction

Invasive pulmonary aspergillosis (IPA) is a well-defined issue in immunocompromised patients, especially in relation to hematologic malignancies and transplantation. Acute respiratory distress syndrome (ARDS) due to severe viral infections, especially influenza disease, increases patients’ susceptibility to bacterial and fungal superinfections, including IPA [1]. This relationship between influenza and IPA has been sporadically conveyed in isolated cases over the past four decades. In the last decade or so, increasingly numerous reports and significantly robust cohort studies have shed light on influenzaassociated pulmonary aspergillosis (IAPA) [5], which is currently a very well-known complication of severe influenza pneumonia with ARDS (19% incidence) [4]. There are several apparent factors involved in this pathogenesis, which are: direct damage to the epithelial–endothelial barrier of the pulmonary alveoli by respiratory viruses and inflammation, enabling Aspergillus to invade tissue; poor airway fungus clearance; immune dysfunction and dysregulation [1,5]—leading to an increased duration of hospitalization and mortality (with mortality rates of up to 51%) [4]

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