Characterization of respiratory microbial dysbiosis in hospitalized COVID-19 patients

Study information

Reviewed Marked as Reviewed by Fatima on 2022/04/20

study design

cross-sectional observational, not case-control

Citation

PMID PubMed identifier for scientific articles.

33850111

DOI Digital object identifier for electronic documents.

10.1038/s41421-021-00257-2

URI

Authors

Zhong H, Wang Y, Shi Z, Zhang L, Ren H, He W, Zhang Z, Zhu A, Zhao J, Xiao F, Yang F, Liang T, Ye F, Zhong B, Ruan S, Gan M, Zhu J, Li F, Li F, Wang D, Li J, Ren P, Zhu S, Yang H, Wang J, Kristiansen K, Tun HM, Chen W, Zhong N, Xu X, Li YM, Li J, Zhao J

Journal

Cell discovery

Year

2021

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.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/20

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): Fatima, Claregrieve1, WikiWorks, Peace Sandy

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: Nasopharynx Nasenrachenraum,Epipharynx,Nasal part of pharynx,Pars nasalis pharyngis,Rhinopharynx,Nasopharynx,nasopharynx

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,cOVID-19

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Mild COVID-19 patients

Group 1 name Corresponds to the case (exposed) group for case-control studies: Severe COVID-19 patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: COVID-19 infected patients admitted to the ICU and requiring mechanical ventilation

Group 0 sample size Number of subjects in the control (unexposed) group: 8

Group 1 sample size Number of subjects in the case (exposed) group: 15

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: DNBSEQ-T7

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)?: No

Alpha Diversity

Richness Number of species: decreased

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/04/20

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2c

Description: Differential abundance in microbial taxa between mild and severe COVID-19 patients

Abundance in Group 1: decreased abundance in Severe COVID-19 patients

NCBI	Quality Control	Links
Veillonella
Neisseria
Streptococcus
Prevotella

Revision editor(s): Claregrieve1

Signature 2

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Reviewed Marked as Reviewed by Fatima on 2022/04/20

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): Claregrieve1

Source: Figure 2c

Description: Differential abundance in microbial taxa between mild and severe COVID-19 patients

Abundance in Group 1: increased abundance in Severe COVID-19 patients

NCBI	Quality Control	Links
Staphylococcus
Escherichia

Revision editor(s): Claregrieve1

Experiment 2

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Reviewed Marked as Reviewed by Fatima on 2022/04/20

Curated date: 2021/07/02

Curator: Claregrieve1

Revision editor(s): LGeistlinger, Claregrieve1, WikiWorks

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Rectum Intestinum rectum,Rectal sac,Terminal portion of intestine,Terminal portion of large intestine,Rectum,rectum

Group 0 sample size Number of subjects in the control (unexposed) group: 7

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: Not specified