Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19

Study information

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

33986253

DOI Digital object identifier for electronic documents.

10.1038/s41392-021-00614-3

URI

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

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/06/30

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks, Atrayees

Subjects

Location of subjects

China

Host species Species from which microbiome was sampled. Contact us to have more species added.

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

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

MGISEQ-2000

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

relative abundances

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

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/13

Curator: Claregrieve1

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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	Quality Control	Links
Arachnia
Mobiluncus
Oribacterium
Oribacterium sp. oral taxon 108
Rothia
Rothia sp. HSID18069
Slackia
Arachnia propionica

Revision editor(s): Claregrieve1

Signature 2

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

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	Quality Control	Links
Veillonella
Liquorilactobacillus nagelii

Revision editor(s): Claregrieve1

Experiment 2

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Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Flu patients

Group 0 sample size Number of subjects in the control (unexposed) group

29

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2021/07/14

Curator: Claregrieve1

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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	Quality Control	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

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

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

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness

increased

Signature 1

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 4c

Description: Differential microbial abundance between flu patients and healthy controls

Abundance in Group 1: increased abundance in Flu patients

NCBI	Quality Control	Links
Veillonella
Liquorilactobacillus nagelii
Limosilactobacillus fermentum
Prevotella amnii

Revision editor(s): Claregrieve1

Signature 2

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

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Source: Figure 4c

Description: Differential microbial abundance between flu patients and healthy controls

Abundance in Group 1: decreased abundance in Flu patients

NCBI	Quality Control	Links
Oribacterium
Arachnia
Rothia
Mobiluncus
Rothia sp. HSID18069
Oribacterium sp. oral taxon 108
Arachnia propionica

Revision editor(s): Claregrieve1

Experiment 4

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

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

Lab analysis

Statistical Analysis

Statistical test

LEfSe

Signature 1

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Curated date: 2021/07/14

Curator: Claregrieve1

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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

NCBI	Quality Control	Links
Actinobaculum
Bifidobacterium
Bulleidia
Cellulomonas
Corynebacterium
Cryptobacterium
Filifactor
Kytococcus
Lachnoanaerobaculum
Mogibacterium
Parvimonas
Propionibacterium
Schaalia
Selenomonas
Streptococcus
Actinomyces
Rothia
Oribacterium
Xylanimonas
Arachnia
Cardiobacterium
Varibaculum
Mobiluncus

Revision editor(s): Claregrieve1

Signature 2

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Curated date: 2021/07/14

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Revision editor(s): Claregrieve1

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	Quality Control	Links
Megasphaera
Veillonella
Abiotrophia

Revision editor(s): Claregrieve1

Experiment 5

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1, WikiWorks, Atrayees

Differences from previous experiment shown

Subjects

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 1 sample size Number of subjects in the case (exposed) group

29

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

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	Quality Control	Links
Streptococcus
Actinomyces
Rothia
Oribacterium
Xylanimonas
Arachnia
Cardiobacterium
Varibaculum

Revision editor(s): Claregrieve1

Signature 2

EditHistoryDelete

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Reviewed Marked as Reviewed by Atrayees on 2023-7-26

Curated date: 2021/07/14

Curator: Claregrieve1

Revision editor(s): Claregrieve1

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	Quality Control	Links
Megasphaera
Veillonella

Revision editor(s): Claregrieve1