Use of Metagenomic Microbial Plasma Cell-Free DNA Next-Generation Sequencing Assay in Outpatient Rheumatology Practice

Abstract Objectives To assess the utility of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay (Karius Test TM ; KT) in the evaluation of patients in an outpatient rheumatology practice. Methods All patients with a KT ordered and obtained by a rheumatology provider in the outpatient setting from 1 January 2020 through 31 December 2022 were retrospectively identified. Demographic, clinical, laboratory, radiologic, histopathology, and microbial studies were abstracted. Indication for KT testing was categorized. KT results were defined based on positive result and clinical relevance regarding the symptoms under investigation at the time of the rheumatologic investigation. Review of cases three months after KT was undertaken to determine clinical outcome. Results 150 patients with a KT were included (53% female, mean age 52 years). The reason for KT was evaluation of atypical presentation of rheumatic disease (80%), assessing flare versus infection in patient on immunosuppression (16.7%), and fever of unknown origin (3.3%). 24 (16%) KTs were positive, 6 of which were considered clinically relevant and altered the final diagnosis and treatment. Of the 126 negative KTs, 5 (4%) were found to have a clinically relevant infection by conventional testing methodologies. Conclusions In this large retrospective cohort study, the most frequent reason for KT utilization was an atypical presentation of rheumatic disease. 25% of positive KTs altered the final diagnosis and treatment, whereas a false-negative rate of 4% was observed. KT has utility in the outpatient rheumatology assessment. Further delineation of which patients are best suited for KT testing remains to be defined. Key messages Use of microbial cell free DNA testing assisted in differentiating between atypical infection and rheumatologic presentation Further studies are needed to define the most optimal patient selection for maximizing mcfDNA technologies in the rheumatology outpatient setting