PONE-D-21-06559

The human microbiome and COVID-19: A systematic review

PLOS ONE

Dear Dr. Yamamoto,

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Even if it seems interesting to study the potential association between the dysbiosis and the immune response to the SARS_CoV_2, it should have been done with more well defined methodology. What is the real scope of the review ? Association between severity of the disease and ? With which criterias ? How the biais are controlled in the studies selected ?

The methodology of the studies retained are not well enough detailed. So it is impossible for the reader to assess the validity of the association described.

Reviewer #2: Yamamoto et al. conducted a systematic literature review on the association between the

microbiome and COVID-19 in humans. They shown that human fecal and respiratory tract microbiome changed in COVID-19 patients with opportunistic pathogen abundance. The quality of the process to conducted this study is excellent. Please find my comments.

- The conclusion need to be more shorter with a highlight in terms of Microbiome dysbiosis.

- Do you think that there is non supplementation with probiotics or prebiotics or fermented food in patients ?

- Can you added your recommendations or can you speculate if patients can be supplemented with probiotics ?

- Can microbiota dysbiosis be uses as a signature of COVID-19 severity (as a biomarker)?

- The aspect of microbiota or microbiome modulation in patients can be discussed.

- The prevention or therapeutic aspects : can you comments please?

- One of the limitation may be the lack of metabolomics studies, can you comments on this point.

Reviewer #3: In this systematic review, the authors collected evidence on alterations in the gut, upper and lower respiratory microbiota in Covid-19 infection.

The study is well conducted and written, offering a good perspective on the work in literature.

The evidence collected is unfortunately of low grade. All the studies collected had an observational design, 14/16 are conducted in China and consider only hospitalized patients. For these reasons, many confounding factors may have altered the results. Moreover, different types of samples and different methods of analysis are used.

Major revision

- Clarify whether unpublished studies were reviewed by a third-party researcher not involved in the study.

Minor revision

- The design and characteristics of the included studies are well described in Table 1. However, they could be reported more clearly in the text.

- In the "Selection criteria and search strategy" paragraph, words used for the research could be placed in quotation marks rather than in parentheses.

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Reviewer #1: No

Reviewer #2: Yes: Marvin Edeas, MD, PhD

Professor of Medicine

Université de Paris, INSERM U1016

Institut Cochin

Department Endocrinology, Metabolism

and Diabetes

Faculté de médecine Cochin-Port Royal

24 rue du Faubourg St Jacques,

75014 Paris-France

Reviewer #3: No

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Attachments

Attachment

Submitted filename: Rev. Microbiota and Covid-19.docx

The human microbiome and COVID-19: A systematic review

PONE-D-21-06559R1

Dear Dr. Mizutani,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Francois Blachier, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors are very clear with the fact that the article is exploratory. It is still quite difficult to extrapolate the observations reported in the review and more, it is not simple to imagine any clinical implications of these observations. Nevertheless, it is interesting to observe that, like for other diseases, dysbiosis is associated with covid19. All the results of the articles included in the review are well reported.

Reviewer #2: Thanks for all your comments and the clarifications. The paper is excellent and will provide a strong contribution to this field.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Marvin EDEAS