Use of the Quantitative Karius® Plasma Next Generation Sequencing Cell-Free Pathogen DNA Test to Detect and Monitor Cytomegalovirus Infection in Allogeneic Stem-Cell Transplant Recipients

Plasma Microbial Cell-Free DNA Sequencing from over 15,000 Patients Identified a Broad Spectrum of Pathogens

“…Identifying optimal utilization, both clinical indications and timing, of the plasma mcfDNA sequencing in future studies to augment clinical decision-making and integration into current testing algorithms ( 17 , 18 , 33 – 35 ) will serve to improve the utility of the test. Examples of such studies include two recently completed prospective, observational clinical trials of the use of the Karius Test to diagnose pneumonia in immunocompromised patients (NCT04047719) ( 36 ) and infections in stem cell transplant inpatients and outpatients over time (NCT02804464) ( 26 ), respectively.…”

“…In addition, infectious disease and hematology/oncology providers comprised most (78%) of the ordering clinicians, aligning with expectations that these clinicians commonly care for critically ill and IC patients with difficult-to-diagnose infections. Constraints of the underlying data structure prevented analyzing the data from the 12% of patients who had repeated testing to determine whether these tests were performed serially to diagnose new suspected infections or to monitor therapy response or conduct pathogen surveillance among immunocompromised patients as described by others ( 8 , 26 , 64 – 66 ). Further, the underlying data structure limited our ability to stratify the results by improvements to the bioinformatics pipeline over the course of the study period.…”

“…Final detections were made after additional filtering was applied, which accounted for read location uniformity, read percent identity, and cross-reactivity originating from higher abundance detections. The microorganism detections that passed these filters were reported along with abundances in MPM, a unique, absolute quantification capability of the Karius Test shown to correlate well with single-analyte qPCR measurements of DNA viruses ( 25 , 26 ).…”