# Microbial and clinical disparities in pneumonia: insights from metagenomic next-generation sequencing in patients with community-acquired and severe pneumonia

## TL;DR

This study uses metagenomic sequencing to identify differences in microbes and clinical features between community-acquired and severe pneumonia patients.

## Contribution

The study reveals distinct microbial and clinical profiles between CAP and SP using mNGS, identifying potential biomarkers like Pseudomonas and Streptococcus.

## Key findings

- SP patients showed higher rates of sepsis, hypotension, and elevated CRP and PCT levels compared to CAP patients.
- Microbial diversity was higher in SP patients, with Pseudomonas linked to SP and Streptococcus to CAP.
- mNGS revealed significant differences in microbial community composition between CAP and SP groups.

## Abstract

Community-acquired pneumonia (CAP) is a major global cause of death, with its varying symptoms and severity complicating diagnosis and treatment. Severe pneumonia (SP), a more critical form of CAP, has higher mortality and often requires intensive care. The identification of clinical markers to differentiate CAP from SP has the potential to improve treatment protocols and patient outcomes. Concurrently, metagenomic next-generation sequencing (mNGS) demonstrates significant promise in pathogen detection and in elucidating microbiome disparities between CAP and SP.

This retrospective study analyzed clinical and pathogen data from 204 patients diagnosed with CAP and 25 patients diagnosed with SP in the Department of Respiratory and Critical Care Medicine at the Zengcheng Branch of Nanfang Hospital, Southern Medical University, spanning the period from September 2022 to June 2023. Clinical characteristics were compared, and bronchoalveolar lavage fluid (BALF) samples underwent mNGS for microbial detection and characterization. Statistical analyses, encompassing Chi-square, Fisher’s exact test, Student’s t-test, and LEfSe analysis, were employed to compare clinical and microbiological data between the CAP and SP cohorts.

Patients with SP were significantly older and exhibited higher incidences of sepsis, hypotension, tachycardia, multilobar infiltrates, and consciousness disorders compared to those with CAP. Elevated levels of C-reactive protein (CRP) and procalcitonin (PCT) were more frequently observed in SP patients. mNGS analysis identified diagnostic microbiology profiles between groups. Diverse microbiological profiles (> 5 species) were more common in SP patients (> 30% detection rate). Beta diversity analysis demonstrated significant differences in microbial community composition between CAP and SP groups (p = 0.001), though alpha diversity metrics showed no significant differences. Both LEfSe and ANCOM-BC2 analyses consistently identified Pseudomonas as a potential biomarker for SP and Streptococcus for CAP.

The substantial differences observed in clinical characteristics, pathogen profiles, and microbiomes between patients with CAP and those with SP highlight the imperative need for comprehensive diagnostic methodologies in the management of pneumonia. mNGS has demonstrated substantial utility in informing personalized treatment strategies, with the potential to enhance clinical outcomes. Future research should prioritize elucidating the dynamics of microbial communities and their impact on pneumonia severity, with the objective of refining and optimizing therapeutic strategies.