1. Introduction
Molecular tools as diagnostic criteria for invasive fungal diseases (IFD) has long been questioned because of a lack of reproducibility and insufficient standardization of protocols. Thanks to initiatives such as FPCRI (www.fpcri.eu [1]) and to the dramatic improvement of the quality assessment of molecular technics, Aspergillus PCR is now included in the new EORTC criteria for classification [2]. Regarding intensive care units (ICU) patients, the classification of IFD mainly refers on criteria adapted from neutropenic patients or relies on single center experiences. One algorithm has emerged as a valuable tool to classify invasive aspergillosis (IA) in ICU patients: the AspICU algorithm [3]. This classification is considered as robust because it has been evaluated in patients for whom autopsy results were available, but it is quite awkward to use in routine practice, particularly in COVID-19 patients with clinical and CT-scan signs hard to interpret [4]. Besides, it does not include molecular markers, which are now used routinely [5].
During COVID-19, patients presenting an acute respiratory distress syndrome (ARDS) shared risk factors and underlying diseases classically reported for IA, such as intubation and mechanical ventilation, corticosteroid therapy, immunological storm with high production of inflammatory cytokines. Warnings following preliminary cohort studies from various countries prompted the monitoring of fungal colonization and co-infections in SARS-CoV-2-infected patients hospitalized in an ICU. However, the entry criterion for putative IA, according to Blot et al., is an Aspergillus-positive culture endotracheal aspirate, which may lack specificity. In the recent review by Arastehfar et al. [6], many COVID-19-associated pulmonary aspergillosis (CAPA) benefited from galactomannan (GM) testing of bronchoalveolar fluid (BALF) or even of tracheal aspirates (not approved by the manufacturer). However, some laboratories, such as ours, have stopped various manipulations of highly SARS-CoV-2-infected samples in order to limit the exposure of laboratory technicians to viral infection. Then, direct examination of respiratory samples or galactomannan (GM) determination in broncho-alveolar lavage have thus been replaced by the systematic use of molecular tools. While performances of blood biomarkers such as GM, (1-3)β-d-glucan (BDG) or Aspergillus DNA detection are well evaluated in neutropenic patients, their clinical value is far less known in other conditions and still need evaluation in an ICU.
Here, our objective was to evaluate the concordance between molecular detection of Aspergillus in respiratory and culture and concordance between blood PCR and serum GM. We also aimed at assessing the ability of Aspergillus PCRs to help categorizing patients in the continuum of colonization to invasive infection in COVID-19 patients. Arguments to complement AspICU criteria are suggested.