A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia

Jingya Zhao; Xiangyan He; Jiumeng Min; Rosary Sin Yu Yao; Yu Chen; Zhonglin Chen; Yi Huang; Zhongyi Zhu; Yanping Gong; Yusang Xie; Yuping Li; Weiwei Luo; Dongwei Shi; Jinfu Xu; Ao Shen; Qiuyue Wang; Ruixue Sun; Bei He; Yang Lin; Ning Shen; Bin Cao; Lingling Yang; Danyang She; Yi Shi; Jiali Zhou; Xin Su; Hua Zhou; Zhenzi Ma; Hong Fan; Yongquan Lin; Feng Ye; Xifang Nie; Qiao Zhang; Xinlun Tian; Guoxiang Lai; Min Zhou; Jinmin Ma; Jing Zhang; Jieming Qu

doi:10.1016/j.ebiom.2023.104790

A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia

EBioMedicine. 2023 Oct:96:104790. doi: 10.1016/j.ebiom.2023.104790. Epub 2023 Sep 13.

Authors

Jingya Zhao¹, Xiangyan He², Jiumeng Min², Rosary Sin Yu Yao², Yu Chen³, Zhonglin Chen², Yi Huang⁴, Zhongyi Zhu², Yanping Gong², Yusang Xie¹, Yuping Li⁵, Weiwei Luo², Dongwei Shi⁶, Jinfu Xu⁷, Ao Shen², Qiuyue Wang⁸, Ruixue Sun², Bei He⁹, Yang Lin², Ning Shen⁹, Bin Cao¹⁰, Lingling Yang², Danyang She¹¹, Yi Shi¹², Jiali Zhou², Xin Su¹³, Hua Zhou¹⁴, Zhenzi Ma², Hong Fan¹⁵, Yongquan Lin², Feng Ye¹⁶, Xifang Nie², Qiao Zhang¹⁷, Xinlun Tian¹⁸, Guoxiang Lai¹⁹, Min Zhou²⁰, Jinmin Ma²¹, Jing Zhang²², Jieming Qu²³

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China.
² Clin Lab, BGI Genomics, Shenzhen 518083, China; PathoGenesis, BGI Genomics, Shenzhen 518083, China.
³ Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China.
⁴ Department of Pulmonary and Critical Care Medicine, Changhai Hospital, Shanghai, China.
⁵ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Wenzhou Medical College, Zhejiang, China.
⁶ Department of Emergency Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁷ Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
⁸ Department of Pulmonary and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, China.
⁹ Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, China.
¹⁰ Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China.
¹¹ Department of Pulmonary and Critical Care Medicine, The General Hospital of the People's Liberation Army, Beijing, China.
¹² Department of Pulmonary and Critical Care Medicine, Jinling Hospital, Nanjing, China.
¹³ Department of Pulmonary and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
¹⁴ Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital Zhejiang University, Hangzhou, China.
¹⁵ Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Sichuan, China.
¹⁶ Department of Pulmonary and Critical Care Medicine, The First Affiliate Hospital of Guangzhou Medical University, Guangzhou, China.
¹⁷ Department of Pulmonary and Critical Care Medicine, Xinqiao Hospital of Army Medical University, Chongqing, China.
¹⁸ Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Beijing, China.
¹⁹ Department of Pulmonary and Critical Care Medicine, Fuzhou General Hospital, Fuzhou, China.
²⁰ Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China. Electronic address: doctor_zhou_99@163.com.
²¹ Clin Lab, BGI Genomics, Shenzhen 518083, China; PathoGenesis, BGI Genomics, Shenzhen 518083, China. Electronic address: majinmin@genomics.cn.
²² Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: zhang.jing@zs-hospital.sh.cn.
²³ Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China. Electronic address: jmqu0906@163.com.

Abstract

Background: Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients.

Methods: In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study.

Findings: We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98).

Interpretation: In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP.

Funding: National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

Keywords: Metagenomic; Outcome; Severe community-acquired pneumonia (SCAP); Signatures; Transcriptomic.