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Diagnostic value of plasma cell-free DNA metagenomic next-generation sequencing in patients with suspected infections and exploration of clinical scenarios-a retrospective study from a single center.

Shuhong Sun·Zhen Ning·Hongyan Xu·Shanxin Peng·Chunhai Gao·Xiaofeng Hu
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Abstract

BACKGROUND: Plasma cell-free DNA metagenomic next-generation sequencing (mNGS) is a non-invasive comprehensive method for the etiological diagnosis of various infectious diseases. However, research on the early diagnosis and real-world clinical impact of plasma mNGS in patients with suspected infection are still limited. MATERIALS AND METHODS: This study retrospectively included 140 patients with suspected infections who underwent early plasma mNGS and conventional culture testing. Referring to the clinical diagnosis of infectious diseases, the diagnostic performance of plasma mNGS and culture tests was compared, and the application scenarios and clinical effects of plasma mNGS were evaluated. RESULTS: The positive rate of plasma mNGS was significantly higher than that of culture methods (55.71% vs 25.10%, p&#x2009;<&#x2009;0.001) and blood cultures (55.71% vs 12.86%, p&#x2009;<&#x2009;0.001). Regarding clinical diagnosis, the sensitivity of plasma mNGS was significantly higher than that of culture (58.27% vs 37.80%, p&#x2009;=&#x2009;0.002). The combination of mNGS and culture achieved a higher detection sensitivity (69.29%), especially in patients with multi-site co-infections (73.68%) and blood infections (73.17%). Plasma mNGS demonstrated higher sensitivity in patients with procalcitonin (PCT) index > 5&#x2009;ng/ml or human neutrophil lipocalin (HNL) index > 200&#x2009;ng/ml. In terms of treatment, a total of 69 patients (54.33%) benefited from plasma mNGS. CONCLUSION: This study highlights the significant improvement in pathogen detection performance by combining conventional culture with plasma mNGS detection, especially in patients with multi-site co-infections and blood infections. Early use of plasma mNGS as an adjunct to culture can better guide clinicians to initiate appropriate anti-infective therapy.

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HumansRetrospective StudiesFemaleMaleHigh-Throughput Nucleotide SequencingCell-Free Nucleic AcidsMiddle AgedMetagenomicsAgedAdultSensitivity and SpecificityBlood CultureCommunicable DiseasesCoinfectionPlasma cell-free DNAclinical impactinfectious diseasesmetagenomic next-generation sequencingJournal ArticleResearch Support, Non-U.S. Gov't

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Shuhong Sun, Zhen Ning, Hongyan Xu, Shanxin Peng, Chunhai Gao, Xiaofeng Hu. 2026-01-02. Diagnostic value of plasma cell-free DNA metagenomic next-generation sequencing in patients with suspected infections and exploration of clinical scenarios-a retrospective study from a single center.. https://doi.org/10.1080/07853890.2025.2608531

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Adult subjectAged subjectFemale subjectHumans subjectJournal Article subjectJournal Article; Research Support, Non-U.S. Gov't resourceMale subjectMetagenomics subjectMiddle Aged subjectPlasma cell-free DNA subjectinfectious diseases subject

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