Next Generation Sequencing of Microbial Cell-Free DNA for Rapid Noninvasive Diagnosis of Infectious Diseases in Immunocompromised Hosts

Abstract

Background Cell-free DNA (cfDNA) sequencing has emerged as a novel laboratory method for rapid and noninvasive diagnosis in prenatal screening, organ transplant rejection, and tumor detection. We describe a series of immunocompromised patients in which cfDNA sequencing was applied to infectious disease diagnosis. Methods Ten adult patients receiving chemotherapy or status post transplantation followed at the Sylvester Comprehensive Cancer Center with febrile illness or documented infection were enrolled between July 31 and October 2, 2018. As part of the clinical evaluation, 5ml of blood was sent for the Karius® Test (Redwood City, CA) which uses next generation sequencing (NGS) of microbial cfDNA in plasma to identify over 1,000 pathogens including bacteria, DNA viruses and fungi. Results The characteristics of the patients studied are presented in Table 1. The median age was 56 years (range, 20-65) with 60% males. Except for a kidney transplant recipient, all other patients had underlying hematological disease and/or had received a hematopoietic cell transplant. All patients were receiving antimicrobials at the time of plasma sample collection. Three patients had neutropenia (absolute neutrophil count Conclusion These data support the clinical utility of NGS-based detection of microbial cfDNA in peripheral blood for rapid noninvasive diagnosis of infections in immunocompromised hosts. Larger studies are needed to validate these findings.