Plasma cell-free metagenomic next generation sequencing in the clinical setting for the diagnosis of infectious diseases: a systematic review and meta-analysis

Abstract

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: Karius; cell-free DNA; diagnostics; meta-analysis; metagenomic next generation sequencing.