Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity

Yifei Shen; Wenxin Qu; Fei Yu; Dan Zhang; Qianda Zou; Dongsheng Han; Mengxiao Xie; Xiao Chen; Lingjun Yuan; Bin Lou; Guoliang Xie; Ruonan Wang; Xianzhi Yang; Weizhen Chen; Qi Wang; Yun Teng; Yuejiao Dong; Li Huang; Jiaqi Bao; Chang Liu; Wei Wu; Enhui Shen; Longjiang Fan; Michael P Timko; Shufa Zheng; Yu Chen

doi:10.1080/19490976.2023.2223340

Dynamic associations between the respiratory tract and gut antibiotic resistome of patients with COVID-19 and its prediction power for disease severity

Gut Microbes. 2023 Jan-Dec;15(1):2223340. doi: 10.1080/19490976.2023.2223340.

Authors

Yifei Shen^{1

2

3}, Wenxin Qu^{1

2

3}, Fei Yu^{1

2

3}, Dan Zhang^{1

2

3}, Qianda Zou¹, Dongsheng Han^{1

2

3}, Mengxiao Xie¹, Xiao Chen^{1

2

3}, Lingjun Yuan¹, Bin Lou^{1

2

3}, Guoliang Xie^{1

2

3}, Ruonan Wang^{1

2

3}, Xianzhi Yang^{1

2

3}, Weizhen Chen^{1

2

3}, Qi Wang^{1

2

3}, Yun Teng^{1

2

3}, Yuejiao Dong^{1

2

3}, Li Huang^{1

2

3}, Jiaqi Bao^{1

2

3}, Chang Liu¹, Wei Wu⁴, Enhui Shen⁵, Longjiang Fan⁵, Michael P Timko⁶, Shufa Zheng^{1

2

3

4}, Yu Chen^{1

2

3

4}

Affiliations

¹ Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China.
³ Institute of Laboratory Medicine, Zhejiang University, Hangzhou, China.
⁴ State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
⁵ Institute of Bioinformatics, Zhejiang University, Hangzhou, China.
⁶ Departments of Biology and Public Health Sciences, University of Virginia, Charlottesville, VA, USA.

Abstract

The antibiotic resistome is the collection of all antibiotic resistance genes (ARGs) present in an individual. Whether an individual's susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. We recruited 66 patients with COVID-19 at three disease stages (admission, progression, and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.

Keywords: COVID-19; Dynamic association; antibiotic resistome; disease severity; gut; prediction; respiratory tract.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents
COVID-19*
Gastrointestinal Microbiome*
Humans
Leukocytes, Mononuclear
Patient Acuity
Respiratory System
Vancomycin

Substances

Anti-Bacterial Agents
Vancomycin

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant numbers 81971919 and 82072377] and Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar [LR23H200002].