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

Abstract

Objective: To assess the utility of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay (Karius Test [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 January 1, 2020, through December 31, 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 3 months after KT was undertaken to determine clinical outcome.

Results: One hundred fifty patients with a KT were included (52.7% female, mean age 52 years). The reason for KT was evaluation of atypical presentation of rheumatic disease (80%), assessing flare vs infection in patients on immunosuppression (16.7%), and fever of unknown origin (3.3%). Twenty-four (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.

Conclusion: In this large retrospective cohort study, the most frequent reason for KT utilization was an atypical presentation of rheumatic disease. One out of 4 positive KTs altered the final diagnosis and treatment. False negative rates were low. KT has utility in outpatient rheumatology assessments. Further delineation of which patients are best suited for KT testing remains to be defined.