Simultaneous Detection of Pathogens and Tumors in Patients With Suspected Infections by Next-Generation Sequencing

Background Differential diagnosis of patients with suspected infections is particularly difficult, but necessary for prompt diagnosis and rational use of antibiotics. A substantial proportion of these patients have non-infectious diseases that include malignant tumors. This study aimed to explore the clinical value of metagenomic next-generation sequencing (mNGS) for tumor detection in patients with suspected infections. Methods A multicenter, prospective case study involving patients diagnosed with suspected infections was conducted in four hospitals in Shanghai, China between July 2019 and January 2020. Based upon mNGS technologies and chromosomal copy number variation (CNV) analysis on abundant human genome, a new procedure named Onco-mNGS was established to simultaneously detect pathogens and malignant tumors in all of the collected samples from patients. Results Of 140 patients screened by Onco-mNGS testing, 115 patients were diagnosed with infections; 17 had obvious abnormal CNV signals indicating malignant tumors that were confirmed clinically. The positive percent agreement and negative percent agreement of mNGS testing compared to clinical diagnosis was 53.0% (61/115) and 60% (15/25), vs. 20.9% (24/115) and 96.0% (24/25), respectively, for conventional microbiological testing (both P < 0.01). Klebsiella pneumoniae (14.8%, 9/61) was the most common pathogen detected by mNGS, followed by Escherichia coli (11.5%, 7/61) and viruses (11.5%, 7/61). The chromosomal abnormalities of the 17 cases included genome-wide variations and local variations of a certain chromosome. Five of 17 patients had a final confirmed with malignant tumors, including three lung adenocarcinomas and two hematological tumors; one patient was highly suspected to have lymphoma; and 11 patients had a prior history of malignant tumor. Conclusion This preliminary study demonstrates the feasibility and clinical value of using Onco-mNGS to simultaneously search for potential pathogens and malignant tumors in patients with suspected infections.