Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients

Cell Discovery

Weijun Chen¹  Zhun Shi²  Xun Xu³  Fuqiang Li⁴  Jian Wang⁵  Huanming Yang⁶  Huahui Ren⁷  Huanzi Zhong⁷  Karsten Kristiansen⁷  Fangming Yang⁸  Shida Zhu⁹  Tianzhu Liang^1,10  Daxi Wang^1,10  Peidi Ren^1,10  Jiandong Li^1,11  Junhua Li^1,12  Jiahui Zhu^1,13  Fei Xiao^1,14  Hein Min Tun^1,15  Lu Zhang^1,16  Yanqun Wang^1,17  Fang Li^1,17  Yi-min Li^1,17  Mian Gan^1,17  Feng Ye^1,17  Jingxian Zhao^1,17  Weiqun He^1,17  Zhaoyong Zhang^1,17  Nanshan Zhong^1,17  Airu Zhu^1,17  Jincun Zhao^1,18  Bei Zhong^1,19  Shicong Ruan^2,20 

[1] BGI Education Center, University of Chinese Academy of Sciences, 518083, Shenzhen, China;BGI PathoGenesis Pharmaceutical Technology Co., Ltd., BGI-Shenzhen, 518083, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, 518120, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI-Shenzhen, 518083, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;James D. Watson Institute of Genome Science, 310008, Hangzhou, China;BGI-Shenzhen, 518083, Shenzhen, China;James D. Watson Institute of Genome Science, 310008, Hangzhou, China;Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, BGI-Shenzhen, 518120, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100, Copenhagen, Denmark;BGI-Shenzhen, 518083, Shenzhen, China;School of Future Technology, University of Chinese Academy of Sciences, 101408, Beijing, China;BGI-Shenzhen, 518083, Shenzhen, China;Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, BGI-Shenzhen, 518120, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, 518083, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, 518083, Shenzhen, China;BGI Education Center, University of Chinese Academy of Sciences, 518083, Shenzhen, China;BGI-Shenzhen, 518083, Shenzhen, China;Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, 518083, Shenzhen, China;School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China;BGI-Shenzhen, 518083, Shenzhen, China;State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 210096, Nanjing, China;Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, 519000, Zhuhai, Guangdong, China;HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China;Institute of Infectious disease, Guangzhou Eighth People’s Hospital of Guangzhou Medical University, 510060, Guangzhou, Guangdong, China;Guangzhou Customs District Technology Center, 510700, Guangzhou, China;State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, 510120, Guangzhou, Guangdong, China;State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, 510120, Guangzhou, Guangdong, China;Institute of Infectious disease, Guangzhou Eighth People’s Hospital of Guangzhou Medical University, 510060, Guangzhou, Guangdong, China;The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guangdong, China;Yangjiang People’s Hospital, Yangjiang, Guangdong, China;

DOI  :  10.1038/s41421-021-00257-2

来源: Springer

【 摘 要 】

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic of Coronavirus disease 2019 (COVID-19). However, the microbial composition of the respiratory tract and other infected tissues as well as their possible pathogenic contributions to varying degrees of disease severity in COVID-19 patients remain unclear. Between 27 January and 26 February 2020, serial clinical specimens (sputum, nasal and throat swab, anal swab and feces) were collected from a cohort of hospitalized COVID-19 patients, including 8 mildly and 15 severely ill patients in Guangdong province, China. Total RNA was extracted and ultra-deep metatranscriptomic sequencing was performed in combination with laboratory diagnostic assays. We identified distinct signatures of microbial dysbiosis among severely ill COVID-19 patients on broad spectrum antimicrobial therapy. Co-detection of other human respiratory viruses (including human alphaherpesvirus 1, rhinovirus B, and human orthopneumovirus) was demonstrated in 30.8% (4/13) of the severely ill patients, but not in any of the mildly affected patients. Notably, the predominant respiratory microbial taxa of severely ill patients were Burkholderia cepacia complex (BCC), Staphylococcus epidermidis, or Mycoplasma spp. (including M. hominis and M. orale). The presence of the former two bacterial taxa was also confirmed by clinical cultures of respiratory specimens (expectorated sputum or nasal secretions) in 23.1% (3/13) of the severe cases. Finally, a time-dependent, secondary infection of B. cenocepacia with expressions of multiple virulence genes was demonstrated in one severely ill patient, which might accelerate his disease deterioration and death occurring one month after ICU admission. Our findings point to SARS-CoV-2-related microbial dysbiosis and various antibiotic-resistant respiratory microbes/pathogens in hospitalized COVID-19 patients in relation to disease severity. Detection and tracking strategies are needed to prevent the spread of antimicrobial resistance, improve the treatment regimen and clinical outcomes of hospitalized, severely ill COVID-19 patients.

【 授权许可】

CC BY