Clinical evaluation of metagenomic next-generation sequencing for detecting pathogens in bronchoalveolar lavage fluid collected from children with community-acquired pneumonia

Abstract

This study is to evaluate the usefulness of pathogen detection using metagenomic next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) specimens from children with community-acquired pneumonia (CAP). We retrospectively collected BALF specimens from 121 children with CAP at Tianjin Children's Hospital from February 2021 to December 2021. The diagnostic performances of mNGS and conventional tests (CT) (culture and targeted polymerase chain reaction tests) were compared, using composite diagnosis as the reference standard. The results of mNGS and CT were compared based on pathogenic and non-pathogenic organisms. Pathogen profiles and co-infections between the mild CAP and severe CAP groups were also analyzed. The overall positive coincidence rate was 86.78% (105/121) for mNGS and 66.94% (81/121) for CT. The proportion of patients diagnosed using mNGS plus CT increased to 99.18%. Among the patients, 17.36% were confirmed only by mNGS; Streptococcus pneumoniae accounted for 52.38% and 23.8% of the patients were co-infected. Moreover, Bordetella pertussis and Human bocavirus (HBoV) were detected only using mNGS. Mycoplasma pneumoniae, which was identified in 89 (73.55%) of 121 children with CAP, was the most frequent pathogen detected using mNGS. The infection rate of M. pneumoniae in the severe CAP group was significantly higher than that in the mild CAP group (P = 0.007). The symptoms of single bacterial infections (except for mycoplasma) were milder than those of mycoplasma infections. mNGS identified more bacterial infections when compared to the CT methods and was able to identify co-infections which were initially missed on CT. Additionally, it was able to identify pathogens that were beyond the scope of the CT methods. The mNGS method is a powerful supplement to clinical diagnostic tools in respiratory infections, as it can increase the precision of diagnosis and guide the use of antibiotics.

The rapid detection of respiratory pathogens in critically ill children

“…An alternative rapid diagnostic method is next-generation metagenomic sequencing (NGS), which has the advantage of being unrestricted in the potential pathogens it may detect. Paediatric studies of NGS describe it as a sensitive test, but it is difficult to determine its clinical application given that studies tend to report positive detection rates in comparison with culture rather than sensitivity and specificity [ 28 – 30 ]. The relevance of low prevalence pathogens and fluctuations in the composition of the respiratory microbiome remains a challenge for the interpretation of molecular diagnostics [ 31 , 32 ].…”

Impact of COVID-19 pandemic on the etiology and characteristics of community-acquired pneumonia among children requiring bronchoalveolar lavage in northern China

“…In a study conducted in southern China, the detection rates of M. pneumoniae using nasopharyngeal swabs of inpatients with acute respiratory infection were also unprecedentedly reduced from 20% in 2019 to 1.0% in 2020[7]. However, another study using BALF from a city in northern China, showed that M. pneumoniae was the most frequently detected pathogen, at a rate of up to 73.55%[24]. Furthermore, the detection of M. pneumoniae further increased despite the NPIs that were adopted during the COVID-19 pandemic.…”

“…Several studies have reported the impact of the COVID-19 pandemic on the pathogen spectrum of respiratory tract infections in children[5-7,24], but the corresponding differences in clinical manifestations have rarely been studied. During the COVID-19 pandemic, we found a decreased proportion of rhonchi, chest indrawing, bilateral lung infiltrates and bronchial lumen morphological changes, but a significantly higher proportion of decreased breath sounds, rales, consolidation, unilateral lung infiltrates and bronchial mucus plugs.…”

The Impact of mNGS Technology in the Etiological Diagnosis of Severe Pneumonia in Children During the Epidemic of COVID-19

“…We have done mNGS studies of bronchoalveolar lavage fluid with community-acquired pneumonia, and found that the positive coincidence rate of the mNGS method for pathogens was much higher than that of the CT method (culture and targeted polymerase chain reaction tests). 5 However, further studies are needed for severe pneumonia. This study aimed to investigate the significance of mNGS examination of alveolar lavage fluid in children with severe pneumonia.…”