Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Ma S, Zhang F, Zhou F, Li H, Ge W, Gan R, Nie H, Li B, Wang Y, Wu M, Li D, Wang D, Wang Z, You Y, Huang Z
Journal
Signal transduction and targeted therapy
Year
2021
COVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil-lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.
Experiment 1
Needs review
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- COVID-19 2019 novel coronavirus,2019 novel coronavirus infection,2019-nCoV,2019-nCoV infection,beta-CoV,beta-CoVs,betacoronavirus,coronavirus disease 2019,SARS-coronavirus 2,SARS-CoV-2,severe acute respiratory syndrome coronavirus 2,severe acute respiratory syndrome coronavirus 2 infectious disease,β-coronavirus,β-CoV,β-CoVs,COVID-19
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- COVID-19 patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Confirmed COVID-19 cases
- Group 0 sample size Number of subjects in the control (unexposed) group
- 28
- Group 1 sample size Number of subjects in the case (exposed) group
- 31
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- MGISEQ-2000
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Signature 1
Needs review
Source: Figure 4c
Description: Differential microbial abundance between COVID-19 patients and healthy controls
Abundance in Group 1: decreased abundance in COVID-19 patients
| NCBI | Links |
|---|---|
| Arachnia | |
| Mobiluncus | |
| Oribacterium | |
| Oribacterium sp. oral taxon 108 | |
| Rothia | |
| Rothia sp. HSID18069 | |
| Slackia | |
| Arachnia propionica |
Revision editor(s): Claregrieve1
Signature 2
Needs review
Source: Figure 4c
Description: Differential microbial abundance between COVID-19 patients and healthy controls
Abundance in Group 1: increased abundance in COVID-19 patients
| NCBI | Links |
|---|---|
| Veillonella | |
| Liquorilactobacillus nagelii |
Revision editor(s): Claregrieve1
Experiment 2
Needs review
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- COVID-19 2019 novel coronavirus,2019 novel coronavirus infection,2019-nCoV,2019-nCoV infection,beta-CoV,beta-CoVs,betacoronavirus,coronavirus disease 2019,SARS-coronavirus 2,SARS-CoV-2,severe acute respiratory syndrome coronavirus 2,severe acute respiratory syndrome coronavirus 2 infectious disease,β-coronavirus,β-CoV,β-CoVs,COVID-19
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Flu patients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- COVID-19 patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Confirmed COVID-19 cases
- Group 0 sample size Number of subjects in the control (unexposed) group
- 29
- Group 1 sample size Number of subjects in the case (exposed) group
- 31
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- MGISEQ-2000
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Signature 1
Needs review
Source: Figure 4c
Description: Differential microbial abundance between COVID-19 patients and other flu patients
Abundance in Group 1: decreased abundance in COVID-19 patients
| NCBI | Links |
|---|---|
| Arachnia | |
| Limosilactobacillus fermentum | |
| Oribacterium | |
| Oribacterium sp. oral taxon 108 | |
| Prevotella amnii | |
| Rothia | |
| Rothia sp. HSID18069 | |
| Slackia | |
| Arachnia propionica |
Revision editor(s): Claregrieve1
Experiment 3
Needs review
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- COVID-19 2019 novel coronavirus,2019 novel coronavirus infection,2019-nCoV,2019-nCoV infection,beta-CoV,beta-CoVs,betacoronavirus,coronavirus disease 2019,SARS-coronavirus 2,SARS-CoV-2,severe acute respiratory syndrome coronavirus 2,severe acute respiratory syndrome coronavirus 2 infectious disease,β-coronavirus,β-CoV,β-CoVs,COVID-19
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Flu patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with influenza B
- Group 0 sample size Number of subjects in the control (unexposed) group
- 29
- Group 1 sample size Number of subjects in the case (exposed) group
- 31
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- MGISEQ-2000
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
Signature 1
Needs review
Source: Figure 4c
Description: Differential microbial abundance between flu patients and healthy controls
Abundance in Group 1: increased abundance in Flu patients
| NCBI | Links |
|---|---|
| Veillonella | |
| Liquorilactobacillus nagelii | |
| Limosilactobacillus fermentum | |
| Prevotella amnii |
Revision editor(s): Claregrieve1
Signature 2
Needs review
Source: Figure 4c
Description: Differential microbial abundance between flu patients and healthy controls
Abundance in Group 1: decreased abundance in Flu patients
| NCBI | Links |
|---|---|
| Oribacterium | |
| Arachnia | |
| Rothia | |
| Mobiluncus | |
| Rothia sp. HSID18069 | |
| Oribacterium sp. oral taxon 108 | |
| Arachnia propionica |
Revision editor(s): Claregrieve1
Experiment 4
Needs review
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- COVID-19 2019 novel coronavirus,2019 novel coronavirus infection,2019-nCoV,2019-nCoV infection,beta-CoV,beta-CoVs,betacoronavirus,coronavirus disease 2019,SARS-coronavirus 2,SARS-CoV-2,severe acute respiratory syndrome coronavirus 2,severe acute respiratory syndrome coronavirus 2 infectious disease,β-coronavirus,β-CoV,β-CoVs,COVID-19
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- COVID-19 patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Confirmed COVID-19 cases
- Group 0 sample size Number of subjects in the control (unexposed) group
- 28
- Group 1 sample size Number of subjects in the case (exposed) group
- 31
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- MGISEQ-2000
Statistical Analysis
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Signature 1
Needs review
Source: Figure 2a-b
Description: Differential microbial abundance between COVID-19 patients and healthy controls by LefSe
Abundance in Group 1: decreased abundance in COVID-19 patients
Revision editor(s): Claregrieve1
Signature 2
Needs review
Source: Figure 2a-b
Description: Differential microbial abundance between COVID-19 patients and healthy controls by LefSe
Abundance in Group 1: increased abundance in COVID-19 patients
| NCBI | Links |
|---|---|
| Megasphaera | |
| Veillonella | |
| Abiotrophia |
Revision editor(s): Claregrieve1
Experiment 5
Needs review
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Oropharynx Mesopharynx,Oral part of pharynx,Pars oralis pharyngis,Oropharynx
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- COVID-19 2019 novel coronavirus,2019 novel coronavirus infection,2019-nCoV,2019-nCoV infection,beta-CoV,beta-CoVs,betacoronavirus,coronavirus disease 2019,SARS-coronavirus 2,SARS-CoV-2,severe acute respiratory syndrome coronavirus 2,severe acute respiratory syndrome coronavirus 2 infectious disease,β-coronavirus,β-CoV,β-CoVs,COVID-19
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Flu patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with influenza B
- Group 0 sample size Number of subjects in the control (unexposed) group
- 28
- Group 1 sample size Number of subjects in the case (exposed) group
- 29
Lab analysis
- Sequencing type
- WMS
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- MGISEQ-2000
Statistical Analysis
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- Yes
Signature 1
Needs review
Source: Figure 2a
Description: Differential microbial abundance between flu patients and healthy controls by LefSe
Abundance in Group 1: decreased abundance in Flu patients
| NCBI | Links |
|---|---|
| Streptococcus | |
| Actinomyces | |
| Rothia | |
| Oribacterium | |
| Xylanimonas ⚠ | |
| Arachnia | |
| Cardiobacterium | |
| Varibaculum ⚠ |
Revision editor(s): Claregrieve1
Signature 2
Needs review
Source: Figure 2a
Description: Differential microbial abundance between flu patients and healthy controls by LefSe
Abundance in Group 1: increased abundance in Flu patients
| NCBI | Links |
|---|---|
| Megasphaera | |
| Veillonella |
Revision editor(s): Claregrieve1
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