Metagenomic Next - Generation Sequencing Detected Neoplasm in Patients Suspected of Infectious Disease

Background: Microbial infection and malignant tumor may present with overlapping symptoms and clinicians often face the challenge in differential diagnosis of febrile patients suspected of infectious diseases. However, timely diagnosis is crucial for rational use of antibiotics, and a tool that can simultaneously detect tumor and infection may greatly improve the efficiency of clinical diagnosis. This study investigated the utility of metagenomic Next-Generation Sequencing, which is usually used for pathogen detection, in differential diagnosis.Methods: We enrolled eleven patients from Nov. 2020 to May 2022. Two participants had been diagnosed with cancer prior to hospitalization and the rest of cases were thought to have microbial infections during initial examinations. Specimens including body fluids and biopsy were acquired and sent for conventional microbiological tests, metagenomic Next-Generation Sequencing and pathological examinations.Findings: Neoplasms were identified via copy number analysis in all patients and tumor was pathologically confirmed. The types of tumors included solid tumors (i.e. lung adenocarcinoma, brain tumor) and hematological malignancies (i.e. lymphoma, leukemia). Moreover, metagenomic sequencing detected pathogens in seven of the patients, and three of the patients got severe infectious disease.Interpretation: For febrile patients suspected of infections, mNGS can serve as a useful tool to provide timely differential diagnosis by incorporating host chromosomal CNV analysis for the detection of both neoplasms and pathogens in a single test. Funding Information: The study was supported by the National Natural Science Foundation of China [grant numbers 82072380, 81871734, 82002236]; research foundation for advanced talents of Guangdong Provincial People’s Hospital [grant number KJ012021097].Declaration of Interests: None of the authors has any conflict of interest to disclose.Ethics Approval Statement: We received approval by the board of Ethics at the Lingnan Hospital, Branch of the Third Affiliated Hospital of Sun Yat-sen University and Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences.