Clinical impact of metagenomic next-generation sequencing of peripheral blood for the diagnosis of invasive mucormycosis: a single-center retrospective study

ABSTRACT This study aims to assess the usefulness of peripheral blood metagenomic next-generation sequencing (mNGS) in diagnosing invasive mucormycosis (IM). We conducted a retrospective analysis of clinical data from 73 patients with mucorales sequences detected by peripheral blood mNGS at the First Affiliated Hospital, Zhejiang University School of Medicine, between February 2021 and December 2022. We examined data on risk factors, clinical symptoms, imaging characteristics, pathogenic findings, clinical diagnoses, and treatment outcomes. Among the 73 patients with mucorales sequences detected by peripheral blood mNGS, 7 cases were confirmed, 12 were probable, 34 were possible, and 20 were false positives, based on the diagnostic criteria for IM. Among the 34 possible cases, patients exhibited risk factors, clinical symptoms, imaging features, and prognoses consistent with IM. In 7 out of the 12 probable cases, the same mucorale nucleic acid was found in peripheral blood mNGS samples collected at an average interval of 8.1 days. In the remaining 20 patients, mucorales nucleic acid was detected in peripheral blood mNGS, but they lacked risk factors or clinical features of mucorales infection and lacked other pathological evidence, leading to a judgment of false positive. The positive predictive value of peripheral blood mNGS for diagnosing invasive mucormycosis in the cases studied was 72.6%. Peripheral blood mNGS testing provides valuable insights for diagnosing invasive mucormycosis. However, it should be used in conjunction with risk factors, clinical features, and other pathogenic test results to make a comprehensive assessment. IMPORTANCE Given the high fatality rates, prompt and accurate identification of the fungal culprit is crucial, emphasizing the need for invasive mucormycosis. Unfortunately, mucormycosis lacks definitive biomarkers, depending primarily on smears, cultures, or pathology, all necessitating invasive specimen collection from the infection site. However, obtaining valid specimens early in critically ill patients poses substantial risks and challenges. Whether peripheral blood metagenomic next-generation sequencing (mNGS) can enhance early mucormycosis diagnosis, especially when direct specimen collection from the infection site is challenging, is warranted. This is a large-scale clinical study conducted to evaluate the utility and clinical impact of mNGS of peripheral blood for the diagnosis of invasive mucormycosis. We believe our study provided both novelty in translational medicine and a great value for the medical community to understand the strengths and limitations of mNGS of peripheral blood as a new diagnostic tool for the diagnosis and management of invasive mucormycosis.