Plasma Cell-Free Metagenomic Next Generation Sequencing in the Clinical Setting for the Diagnosis of Infectious Diseases: A Systematic Review and Meta-Analysis

Elsevier

Available online 20 October 2022, 115838

Diagnostic Microbiology and Infectious DiseaseAbstract

Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) is a non-invasive method that may be able to identify thousands of pathogens through a hypothesis-free approach. There is a lack of consensus on how this test compares to conventional microbiologic testing. We conducted a systematic review and meta-analysis of published studies evaluating the accuracy of plasma cf-mNGS in hospitalized patients and present pooled estimates of the positive (PPA) and negative percent agreement (NPA) compared to a composite reference standard that included all conventional microbiological testing and clinical history as assessed by an adjudication panel or clinical treatment team. Five retrospective studies (n= 552) were included. The majority of the patients (56-88%) were immunocompromised. The pooled PPA was 67% (95% CI, 54-81%) and the pooled NPA was 70% (95% CI, 63-77%). The pooled diagnostic performance characteristics suggest that cf-mNGS provides limited evidence for ruling in or out the presence of infection as commonly used.

Keywords

cell-free DNA

metagenomic next generation sequencing

Karius

diagnostics

meta-analysis

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