Cell-free DNA metagenomic next generation sequencing for the diagnosis of infectious diseases: a retrospective assessment of clinical utility in a tertiary and quaternary care facility

Background We sought to retrospectively assess the clinical utility of a commercially available plasma cell-free DNA (cfDNA) metagenomic next generation sequencing (mNGS) known as the Karius test (KT), for the diagnosis of infectious diseases, stratified by clinical syndrome. Methods Retrospective chart review and abstraction were performed to assess the clinical impact of KT. Descriptive statistics were used to characterize the results of the KT in conjunction with host parameters. Results This study included 120 KT results from 114 patients, collected from September 1, 2021, through August 31 st , 2024, at our academic medical center which includes a 401-bed acute care, academic hospital offering quaternary care, in addition to a 60-bed cancer hospital. The KT demonstrated clinical utility in 28.3% of all 120 cases, with 67.5% yielding no impact, 2.50% negative impact, and 1.67% indeterminate impact, though impact proportions were syndrome dependent. Host immune competency was not a reliable predictor of KT impact, consistent with previous studies. Overall, the KT yielded 100 unique organisms with a 67.5% positivity rate. Conclusion Taken together, these data suggest that despite the relatively high rate of organism detection by KT, clinical impact is modest. Based on effect size analyses, this study identified several clinical scenarios that warrant larger scale prospective investigation to more completely elucidate high-yield use cases of KT.