5. Diagnostic Workup for Accurate Identification of CAPA
The optimal diagnostic algorithm for diagnosing CAPA is currently unknown, and this question is actively being investigated in an ongoing multinational explorative trial in conjunction with the European Confederation of Medical Mycology (ECMM). The most common methods to date include attempting to recover Aspergillus spp. on culture media of bronchoalveolar fluid (BALF) and tracheal aspirate, as well as utilizing serologic biomarker testing such as the conventional Galactomannan (GM) from BALF, tracheal aspirate, and serum specimens. Other diagnostic tests that may prove useful also include Aspergillus PCR, serum (1→3)-β-d-glucan (BDG), the Aspergillus galactomannan lateral flow assay (LFA) (IMMY, Norman, Oklahoma, USA), and the Aspergillus-specific lateral-flow device (LFD) test (OLM Diagnostics, Newcastle Upon Tyne, UK).
In published cases and case series from Germany [50,61], France [51,57,58], Italy [59], Austria [60], Belgium [52], Australia [63], and the Netherlands [47], CAPA was most commonly mycologically diagnosed by either culture from BALF or tracheal aspirate and/or based on a positive GM or LFD from BALF or tracheal aspirate (Table 1). Across published cases, Aspergillus culture was positive in 29/35 (83%) of patients; of those with a positive culture and a reported source, 16/29 (55%) were recovered from—often undirected—BALF, 12/29 (41%) from tracheal aspirate, and 1/29 (3%) from sputum. In those where a BALF GM test was performed, 14/23 (61%) had a titer ≥1.5 ODI and 16/23 (70%) a titer ≥0.5 ODI, while 6/28 (21%) of those with serum GM results had a titer > 0.5 ODI. PCR from respiratory specimens or tissue was positive in 10/14 (71%) and LFD from tracheal secretion positive in 1/1 of patients.
Thus, BALF and tracheal aspirate culture and conventional GM testing from BALF appear to be the most promising diagnostic modalities. Still, bronchoscopy can potentially aerosolize virus [78] in patients with COVID-19 infection, thus posing a risk to patients and personnel from SARS-CoV-2 virus. In many centers, the role of bronchoscopy is limited and testing from blood samples may be safer and more optimal and allow also for twice weekly screening which has been implemented in many centers [52], although the low levels of GM positivity from serum in these reports is discouraging, and the sensitivity of serum BDG, which is less specific for IA, was only 44% (4/9).