Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia

Abstract

Background: Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease's complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques.

Results: We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes.

Conclusions: Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP.

Trial registration: Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628 .

Keywords: Clinical metagenomics; Clinical study; Community-acquired pneumonia; Next-generation sequencing; Polymicrobial infections.

Fig. 1

Key characteristics of patients and specimens. a Enrollment criteria and study design; (b) Comparison of APACHE II scores between the control and mNGS groups (mean of 12.6 vs 11.1, error bars represented standard deviations); (c) Specimens collected from the control (n = 109) and mNGS (n = 104) groups. Abbreviations: BALF, bronchoalveolar lavage fluid; CSF, cerebrospinal fluid. n.s., not significant, * indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001 by student’s t-test

Fig. 2

Diagnostic performance of mNGS assay for pathogen detection. a Rates of pathogen detection in the control and mNGS groups, summarized from testing with all collected samples; (b) Consistency between mNGS test results and clinical diagnosis; (c) Culture and mNGS detection rates for pathogens in mNGS group; (d) Differential spectrums of bacterial and fungal organisms identified between mNGS and culture; (e) Numbers of specific organisms identified by mNGS and the percentages of each microbial type; (f) Patients with single and multiple pathogens as identified by mNGS; (g) Types of pathogens shown in panel F; (h) Concordance in mNGS results between paired BALF and blood specimens. n.s., not significant, * indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001 by chi-square test

Fig. 3

Impact on clinical outcomes by mNGS. a Changes in mortality rate (b), complete symptom resolution, and (c) duration of mechanical ventilation in control group (n = 100); mNGS group (mNGS, n = 59); those whose clinical management were changed based on mNGS results (Management Changed, n = 11); and those whose treatment was either changed (i.e. the 11 cases in the group of Management Changed) or confirmed (Management Changed/Confirmed, n = 35). d Assessment of liver and kidney function in patients with favorable clinical outcome in the mNGS group. Comparisons made between results at admission and at discharge. *, **, *** indicated P-values < 0.05, < 0.01 and < 0.001 respectively, by chi-square test and adjusted for multiple testing. ALT = alanine aminotransferase; AST = aspartate aminotransferase; ALB = albumin; BUN = blood urea nitrogen; Cr = creatinine