PONE-D-24-16835SARS-CoV-2 impairs male fertility by targeting semen quality and testosterone level: A Systematic Review and Meta-analysisPLOS ONE

Dear Dr. Akhigbe,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

I see high potential that this manuscript becomes an important reference. Both reviewers provide constructive suggestions for revisions.

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PLOS ONE

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2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1227836/full

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Additional Editor Comments:

This is an interesting paper describing the effects of a Covid infection on the male reproductive system. Both referees are very positive but have some suggestions for minor revsion.

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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

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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: Dear Authors,

Congratulations for this interesting piece of research.

Some items worth considering:

1. It might be worth mentioning that duration of the infection and time between infection and semen collection might have an effect on the study outcomes. Based on current literature and on textbook knowledge, high fever might have a transient effect on semen analysis which might (or might not) be temporary.

2. Likewise, it might be worth mentioning if the studies were performed in early 2020, after introduction of COVID-19 vaccines, or following infection by the most recent and less dangerous variants of COVID-19.

3. Some of the studies were done before the release of the 2021 WHO manual. It might also be worth highlighting this difference, since it can affect the interpretation of the results, and maybe consider this when performing subgroup analyses.

Reviewer #2: The manuscript to be assessed is a systematic review and meta-analysis of the influence of SARS-CoV-2 infection on male fertility. There are already meta-analyses on this topic, but the authors explain very well that, in their view, there are methodological weaknesses in the already published meta-analyses that they have explicitly addressed in their work.

Overall, this is a methodologically very well conducted meta-analysis. The methodological steps and statistical analyses carried out are very well documented and openly communicated. The associated illustrations, especially the forest plots, are very detailed and comprehensive, which seems necessary due to the large number of parameters analysed.

Overall, in my view, this is a very mature manuscript for which I would like to congratulate the authors. The lack of originality in terms of existing publications is addressed by the authors and clearly explained what the methodological changes are here. As a suggestion for improvement, I would only add 2 aspects to the discussion.

1) I miss the discussion of the longitudinal aspect here, i.e. the duration of a potentially negative influence of SARS-CoV-2 infection on the reproductive functions of men, also with regard to the control intervals of the underlying studies.

2) in my view, it should also be discussed to what extent a SARS-CoV-2 infection represents a special feature compared to other systemically active viral infections, some of which are very severe (e.g. influenza), or whether this is not to be expected independently of the virus type.

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Reviewer #1: No

Reviewer #2: No

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SARS-CoV-2 impairs male fertility by targeting semen quality and testosterone level: A Systematic Review and Meta-analysis

PONE-D-24-16835R1

Dear Dr. Akhigbe,

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,

Stefan Schlatt

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: Yes

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: (No Response)

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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: (No Response)

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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: Dear Authors,

Thanks for addressing my previous concerns. I believe that this manuscript does not need any further edits.

Reviewer #2: Congratulations to this nice piece of science. After revision absolutely worthwhile for publication in my view

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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: No

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