Plasma metagenomic next-generation sequencing (mNGS) testing is a promising diagnostic modality for infectious diseases, but its real-world clinical impact is poorly understood. We reviewed patients who had undergone plasma mNGS at a general hospital to evaluate the clinical utility of plasma mNGS testing. A total of 76.9% (113/147) of plasma mNGS tests had a positive result. A total of 196 microorganisms (58) were identified and reported, of which 75.6% (148/196) were clinically relevant. The median stringent mapped read number (SMRN) of clinically relevant organisms was 88 versus 22 for irrelevant organisms (P = 0.04). Based on the clinically adjudicated diagnosis, the positive and negative percent agreements of plasma mNGS testing for identifying a clinically defined infection were 95.2% and 67.4%, respectively. The plasma mNGS results led to a positive impact in 83 (57.1%) patients by diagnosing or ruling out infection and initiating targeted therapy. However, only 32.4% (11/34) of negative mNGS tests showed a positive impact, suggesting that plasma mNGS testing alone may not be a powerful tool to rule out infection in clinical practice. In the subset of 37 patients positive for both plasma mNGS and conventional testing, mNGS identified the pathogen(s) 2 days (IQR = 0.75 to 4.25) earlier than conventional testing. mNGS enables pathogen identification within 24 h, but given that the detection of clinically irrelevant organisms and nearly half of the tests result in no or a negative clinical impact, more clinical practice and studies are required to better understand who and when to test and how to optimally integrate mNGS into the infectious disease diagnostic workup. IMPORTANCE In this study, we show that although plasma mNGS testing significantly improved the detection rate of tested samples, nearly one in four (24.5%, 48/196) mNGS tests reported organisms were not clinically relevant, emphasizing the importance of cautious interpretation and infectious disease consultation. Moreover, based on clinical adjudication, plasma mNGS testing resulted in no or a negative impact in nearly half (43.5%, 64/147) of patients in the current study, indicating that how best to integrate this advanced method into current infectious disease diagnostic frameworks to maximize its clinical utility in real-world practice is an important question. Therefore, recommending plasma mNGS testing as a routine supplement to first-line diagnostic tests for infectious diseases faces great challenges. The decision to conduct mNGS testing should take into account the diagnostic performance, turnaround time and cost-effectiveness of mNGS, as well as the availability of conventional tests.
Keywords: infectious disease; metagenomic next-generation sequencing; pathogen; plasma.