Utility of Plasma Microbial Cell-Free DNA Whole-Genome Sequencing for Diagnosis of Invasive Aspergillosis in Patients With Hematologic Malignancy or COVID-19

Author:

Lee Ki Hyun1,Won Dongju2ORCID,Kim Jinnam1,Lee Jung Ah1,Kim Chang Hyup1,Kim Jung Ho1,Jeong Su Jin1,Ku Nam Su1,Choi Jun Yong1ORCID,Yeom Joon-Sup1,Cho Hyunsoo3,Chung Haerim3,Cheong June-Won3,Lee Seung-Tae2,Jang Ji Eun3,Shin Saeam2ORCID,Ahn Jin Young1

Affiliation:

1. Division of Infectious Diseases, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine , Seoul , Korea

2. Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine , Seoul , Korea

3. Division of Hematology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine , Seoul , Korea

Abstract

Abstract Background We evaluated the clinical accuracy and utility of whole-genome sequencing (WGS) of plasma microbial cell-free DNA (cfDNA) as a novel noninvasive method in diagnosing invasive aspergillosis (IA) in patients with hematologic malignancy (HM) or coronavirus disease 2019 (COVID-19). Methods Adults with HM or COVID-19 and suspected IA were recruited. IA cases were retrospectively diagnosed according to EORTC/MSG definitions and ECMM/ISHAM criteria for HM and COVID-19 patients, respectively. The results of cfDNA WGS were compared with the conventional diagnosis. Results Microbial cfDNA WGS was performed 53 times from 41 participants (19 from HM, 16 from COVID-19, and 7 from the control group). In participants with HM, Aspergillus cfDNA was detected in 100% of proven IA and 91.7% of probable IA cases. In participants with COVID-19, 50.0% of probable IA were positive for Aspergillus in cfDNA WGS. Concordance between Aspergillus cfDNA detection and proven/probable IA conventional diagnosis was significantly higher in participants with HM than in those with COVID-19. IA diagnosed using EORTC/MGS definitions showed significantly high concordance between Aspergillus cfDNA detection and proven/probable IA. Conclusions Aspergillus cfDNA detection strongly correlated with proven/probable IA diagnosed using EORTC/MSG definitions and could be used as an additional diagnostic tool for IA.

Funder

Severance Hospital

National Research Foundation of Korea

Korean Government

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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