Clinical Evaluation of Metagenomic Next-Generation Sequencing and Identification of Risk Factors in Patients with Severe Community-Acquired Pneumonia

Abstract

Purpose

Severe community-acquired pneumonia (SCAP) is the leading cause of death among patients with infectious diseases worldwide. This study aimed to evaluate the effectiveness of metagenomic next-generation sequencing (mNGS) through detecting pathogens in bronchoalveolar lavage fluid (BALF) and identifying risk factors for recovery in SCAP patients.

Patients and Methods

This prospective study recruited 158 SCAP patients admitted to respiratory intensive care unit that were randomly divided into control and study groups, with receiving conventional tests and the same conventional tests plus mNGS, respectively. The diagnostic efficiency of mNGS was evaluated by comparing with conventional tests. Furthermore, univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for recovery in SCAP patients, and a nomogram prediction model was established based on these factors.

Results

Within the study group, the pathogen detection rate was significantly higher with mNGS than that with conventional tests (84.81% vs 45.57%, P < 0.001), with a positive coincidence rate of 94.44%. Acinetobacter baumannii (21.52%, 17/79), Candida albicans (17.72%, 14/79), and Klebsiella pneumonia (15.19%, 12/79) were the top three common pathogens detected by mNGS. Of note, the improvement rate of patients in the study group was significantly higher than that in the control group. The further analysis revealed that the increased levels of interleukin-6, blood urea nitrogen, procalcitonin, the longer length of hospital stay, and bacterial infection were independent risk factors for recovery of SCAP patients, while mNGS detection status was a protective factor. The predictive model showed a good performance for the modeling and validation sets.

Conclusion

Early mNGS exhibited a superior diagnostic efficiency to conventional tests in SCAP patients, which can reduce the risk of death in SCAP patients. Moreover, the clinical factors could also be used for the management and prognosis prediction of SCAP patients.

Keywords:

• severe community-acquired pneumonia
• metagenomic next-generation sequencing
• pathogen
• risk factor

Data Sharing Statement

The datasets generated during and/or analyzed during the current study are not publicly available due to the policy of People’s Hospital of Xinjiang Uygur Autonomous Region but are available from the corresponding author on reasonable request.

Ethics Approval and Informed Consent

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the Ethics Committee of the People’s Hospital of Xinjiang Uygur Autonomous Region and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All experimental protocols were approved by the licensing ethical committee of People’s Hospital of Xinjiang Uygur Autonomous Region. The Ethical Approval No. was KY202010101922. Written informed consent to participate in this study was provided by the participants or their legal guardians.

Acknowledgments

We express our gratitude to the patients and their families included in this study. Also, we are grateful to BGI-Shenzhen for its technical support in metagenomic next-generation sequencing.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This research was supported by Natural Science Foundation Project 2020D01C098 of Xinjiang Uygur Autonomous Region. Special Project for the Construction of Innovative Environment (Talents and Bases) in Xinjiang Uygur Autonomous Region (Talents Special Plan – Tianshan Youth Program) – Training Project 2020Q045 for Outstanding Young Scientific and Technological Talents.