Metagenomic Sequencing in Clinical Infectious Diseases

Research on the Diagnostic Application of Metagenomic Sequencing in Clinical Infectious Diseases

Progress in the diagnosis of infectious pathogens depends on the development of effective methods and the discovery of suitable biomarkers. There are several kinds of methods that have been used in diagnosis of various pathogens, such as microscopic examination, culture, serologic diagnosis or molecular approaches, etc. However, these methods have similar limitations, that is, the single detection of reagents. More importantly, physicians seldom consider infections with rare pathogens. Recently developed metagenomic next-generation sequencing (mNGS) has the capability to overcome limitations of traditional diagnostic tests. This new technology could identify all pathogens directly from sample with a single run in a hypothesis-free and culture-independent manner. Studies have shown that mNGS is more sensitive than traditional culture method in clinical conditions such as blood stream, respiratory and general infections. More importantly, due to unbiased sampling, mNGS is theoretically able to identify not only known but also unexpected pathogens or even discovery novel organisms. It should be noted that mNGS also has some limitations such as human genome contamination and possibly environmental microbial contamination. The vast majority of reads in mNGS are derived from human host. This would impede the overall analytical sensitivity of mNGS for pathogen detection. Host depletion methods or targeted sequencing may help to partially mitigate this disadvantage. As mNGS could not, by itself, define whether the detected microbe is the causative pathogen or environmental microorganism, a multidisciplinary discussion by clinicians, microbiologists as well as the lab technicians is required to interpret the result.

Study Overview

• Status: Completed
• Conditions: Bacterial Infections and Mycoses
• Intervention / Treatment: Diagnostic test: Effects of mNGS on infected patients

• Study Type: Observational
• Enrollment (Actual): 2022097

Contacts and Locations

Study Locations

• China
  • Shandong
    • Liaocheng, Shandong, China, 252000
      • LiaoCheng People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All the enrolled patients have received mNGS testing in clinical practice. Clinical data were rigorously evaluated and summarized, patients' data were compiled until death or hospital discharge.

Description

Inclusion Criteria:

• All the patients have received mNGS testing in clinical practice.

Exclusion Criteria:

• Interruption of patient treatment process and incomplete information

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Infected patients with mNGS; If the patient is suspected of infection, mNGS is performed for testing.	Diagnostic test: Effects of mNGS on infected patients; The impact of mNGS on infected patients, including diagnostic value, drug selection, treatment prognosis, economic burden, etc.
Infected patients without mNGS; The patient is suspected of being infected, and no mNGS test was performed, only other tests were performed.	Diagnostic test: Effects of mNGS on infected patients; The impact of mNGS on infected patients, including diagnostic value, drug selection, treatment prognosis, economic burden, etc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Receiver operating characteristic (ROC) curves evaluate the performance of mNGS and traditional microbiological testing	Receiver operating characteristic (ROC) curves were used to evaluate the performance of the logarithm of reads per kilobase per million mapped reads [lg(RPKM)], genomic coverage, and relative abundance of the organism in predicting the true-positive pathogenic bacteria. Clinical data were rigorously evaluated and summarized to identify promising clinical indices and limitations of the mNGS-based test.	From admission to discharge, 3 weeks

Collaborators and Investigators

• Sponsor: Liaocheng People's Hospital
• Investigators: Study Chair: Shengjun Ma, Dr., LiaoCheng People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2020
• Primary Completion (Actual): October 16, 2021
• Study Completion (Actual): April 20, 2022

Study Registration Dates

• First Submitted: April 24, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: clinical metagenomics; infection diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Mycoses; Bacterial Infections; Bacterial Infections and Mycoses
• Other Study ID Numbers: 2022097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No