Clinical accuracy and utility of plasma microbial cell free DNA whole genome sequencing in the diagnosis of invasive aspergillosis in patients with hematologic malignancies or coronavirus disease.

배경: Dagnosis of invasive aspergillosis (IA) is often difficult due to need for invasive procedures. Next-generation sequencing of plasma microbial cell free DNA (cfDNA) can be a novel non-invasive diagnostic method. We evaluated the clinical accuracy and utility of microbial cfDNA whole genome sequencing (WGS) for diagnosis of IA in patients with hematologic malignancy (HM) or coronavirus disease (COVID-19). 방법: A single-center prospective cohort study was conducted in a tertiary hospital in Korea. We enrolled adult patients with HM or severe COVID-19, who suspected of IA and collected plasma samples. cfDNA was extracted from plasma and WGS was performed. IA diagnosis was retrospectively confirmed according to EORTC/MSG definitions in patients with HM, and modified AspICU criteria in patients with severe COVID-19. The final diagnosis of IA was compared to the results of microbial cfDNA WGS. 결과: Between Mar 2021 and Feb 2022, a total of 64 microbial cfDNA WGS was performed on the plasma samples from 37 participants (19 with HM and 19 with COVID-19) and 7 controls who didn’t have any evidence of fungal infection. In participants with HM, aspergillus cfDNA was detected in 100% (1/1) of proven and 84.6% (11/13) of probable IA cases. In participants with COVID-19, 46.7% (7/15) of probable IA showed positive aspergillus cfDNA. Positive agreement of detection of aspergillus cfDNA versus conventional diagnosis of proven/probable IA was significantly higher in participants with HM compared to COVID-19 (85.7% vs. 46.7%, p=0.011). Fifteen of 19 (78.9%) participants with positive aspergillus cfDNA had exposure to antifungal agents. In 7 participants, non-aspergillus pathogens detected by microbial cfDNA WGS were in accordance with those identified through conventional culture. 결론: Detection of aspergillus cfDNA showed high concordance with conventional diagnostic methods of proven/probable IA in patients with HM and could be a helpful non-invasive approach to IA diagnosis in those populations. [ABSTRACT FROM AUTHOR]