Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19

Study information

Reviewed Marked as Reviewed by Fatima on 2022/05/11

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

32690600

DOI Digital object identifier for electronic documents.

10.1136/gutjnl-2020-322294

URI

Authors

Zuo T, Liu Q, Zhang F, Lui GC, Tso EY, Yeoh YK, Chen Z, Boon SS, Chan FK, Chan PK, Ng SC

Journal

Gut

Year

2021

Keywords:

diagnostic virology, gut inflammation, infectious disease

OBJECTIVE: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19. DESIGN: We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity. RESULTS: Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3' vs 5' end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3' vs 5' end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA. CONCLUSION: This pilot study provides evidence for active and prolonged 'quiescent' GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/05/11

Curated date: 2021/03/04

Curator: Fatima

Revision editor(s): Fatima, Claregrieve1, WikiWorks

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: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces

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: Patients with low-to-none SARS CoV-2 infectivity
Group 1 name Corresponds to the case (exposed) group for case-control studies: Patients with high SARS CoV-2 infectivity
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: SARS CoV-2 infection confirmed by two consecutive RT-OCR tests. High SARS-CoV2 infectivity defined as higher 3' vs 5' end coverage of SARS CoV-2 genome in fecal viral RNA metagenome.
Group 0 sample size Number of subjects in the control (unexposed) group: 15
Group 1 sample size Number of subjects in the case (exposed) group: 15

Lab analysis

Sequencing type: WMS

Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

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
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/05/11

Curated date: 2021/03/04

Curator: Fatima

Revision editor(s): Fatima, Claregrieve1

Source: Figure 4

Description: Differential bacterial species and functional capacities between feces with high severe acute respiratory syndrome coronavirus 2 infectivity and feces with low to-none SARS-CoV-2 infectivity

Abundance in Group 1: decreased abundance in Patients with high SARS CoV-2 infectivity

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Bacteroides stercoris
Lachnospiraceae bacterium
Parabacteroides merdae
Alistipes onderdonkii

Revision editor(s): Fatima, Claregrieve1

Signature 2

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Your review change was submitted

Reviewed Marked as Reviewed by Fatima on 2022/05/11

Curated date: 2021/03/04

Curator: Fatima

Revision editor(s): Fatima, Claregrieve1

Source: Figure 4

Description: Differential bacterial species and functional capacities between feces with high severe acute respiratory syndrome coronavirus 2 infectivity and feces with low to-none SARS-CoV-2 infectivity

Abundance in Group 1: increased abundance in Patients with high SARS CoV-2 infectivity

NCBI	Quality Control	Links
Collinsella aerofaciens
Collinsella tanakaei
Morganella morganii
Streptococcus infantis

Revision editor(s): Fatima, Claregrieve1