Microbial cfDNA NGS for Rapid Noninvasive Diagnosis of Infectious Diseases in Immunocompromised Hosts

Cell-free DNA (cfDNA) sequencing has emerged as an effective laboratory method for rapid and noninvasive diagnosis in prenatal screening testing, organ transplant rejection screening, and oncology liquid biopsies. Here we report our experience using next generation sequencing (NGS) for detection of microbial cfDNA in a cohort of ten immunocompromised patients with febrile neutropenia or deep-seated infection. Among five hematological malignancy patients, for whom a microbiological diagnosis was established, pathogen identification by cfDNA NGS demonstrated 100% positive agreement with conventional diagnostic laboratory methods. Further, cfDNA identified the etiological agent in two patients with culture negative sepsis who had undergone hematopoietic stem cell transplant. These data support the clinical utility of measurement of microbial cfDNA sequencing from peripheral blood for rapid noninvasive diagnosis of infections in immunocompromised hosts.