Lost microbes of COVID-19: Bifidobacterium , Faecalibacterium depletion and decreased microbiome diversity associated with SARS-CoV-2 infection severity
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Abstract
The study objective was to compare gut microbiome diversity and composition in SARS-CoV-2 PCR-positive patients whose symptoms ranged from asymptomatic to severe versus PCR-negative exposed controls.
Design
Using a cross-sectional design, we performed shotgun next-generation sequencing on stool samples to evaluate gut microbiome composition and diversity in both patients with SARS-CoV-2 PCR-confirmed infections, which had presented to Ventura Clinical Trials for care from March 2020 through October 2021 and SARS-CoV-2 PCR-negative exposed controls. Patients were classified as being asymptomatic or having mild, moderate or severe symptoms based on National Institute of Health criteria. Exposed controls were individuals with prolonged or repeated close contact with patients with SARS-CoV-2 infection or their samples, for example, household members of patients or frontline healthcare workers. Microbiome diversity and composition were compared between patients and exposed controls at all taxonomic levels.
Results
Compared with controls (n=20), severely symptomatic SARS-CoV-2-infected patients (n=28) had significantly less bacterial diversity (Shannon Index, p=0.0499; Simpson Index, p=0.0581), and positive patients overall had lower relative abundances of Bifidobacterium (p<0.0001), Faecalibacterium (p=0.0077) and Roseburium (p=0.0327), while having increased Bacteroides (p=0.0075). Interestingly, there was an inverse association between disease severity and abundance of the same bacteria.
Conclusion
We hypothesise that low bacterial diversity and depletion of Bifidobacterium genera either before or after infection led to reduced proimmune function, thereby allowing SARS-CoV-2 infection to become symptomatic. This particular dysbiosis pattern may be a susceptibility marker for symptomatic severity from SARS-CoV-2 infection and may be amenable to preinfection, intrainfection or postinfection intervention.
Trial registration number
NCT04031469 (PCR−) and 04359836 (PCR+).
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SciScore for 10.1101/2021.09.02.21262832: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was conducted in accordance with ethical principles of the Declaration of Helsinki, the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice (GCP), and was approved by the “Ethical and Independent Review Services” (https://www.eandireview.com/) Independent Review Board (IRB).
Consent: All patients provided written informed consent to participate in the study and the study is registered as clinicaltrials.gov NCT04031469. 2.2.
Field Sample Permit: They were instructed to collect 1 mL of fresh stool and place it directly in a Zymo Research DNA/RNA Shield fecal collection tube.Sex as a biological variable not detected. Randomization …SciScore for 10.1101/2021.09.02.21262832: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The study was conducted in accordance with ethical principles of the Declaration of Helsinki, the International Council for Harmonisation (ICH) Harmonised Tripartite Guideline for Good Clinical Practice (GCP), and was approved by the “Ethical and Independent Review Services” (https://www.eandireview.com/) Independent Review Board (IRB).
Consent: All patients provided written informed consent to participate in the study and the study is registered as clinicaltrials.gov NCT04031469. 2.2.
Field Sample Permit: They were instructed to collect 1 mL of fresh stool and place it directly in a Zymo Research DNA/RNA Shield fecal collection tube.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources We compared microbiome differences between the SARS-CoV-2 patients and SARS-CoV-2-negative exposed controls at all taxonomic levels. 2.4. Data Analysis: We assessed differences in relative abundance across taxa between the gut microbiome of SARS-CoV-2 infected patients and exposed controls and calculated Shannon and Simpson index with One Codex’s bioinformatics analysis pipeline using Jupyter notebook in Python. Pythonsuggested: (IPython, RRID:SCR_001658)To evaluate the statistical significance of any variability noted between patients and exposed controls, t-test, ANOVA, and chi-square tests statistics were conducted using R version 3.6.1 (2019-07-05), GraphPad vs. 8, and SigmaPlot 12.0. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)SigmaPlotsuggested: (SigmaPlot, RRID:SCR_003210)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04443075 Completed Alterations of Gut Microbiome in the Frontline Medical Staff… NCT04486482 Completed A Clinical Study to Assess the Physiologic Effects of KB109 … NCT04031469 Recruiting A Non-Interventional Pilot Study to Explore the Role of Gut … Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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