Dear Dr Fang,

Thank you very much for submitting your manuscript "Human infection with respiratory adenovirus in China: a systematic review and meta-analysis" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Ali Rostami

Academic Editor

PLOS Neglected Tropical Diseases

Elvina Viennet

Section Editor

PLOS Neglected Tropical Diseases

***********************

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: Title

It would be good to clarify if this article is a prevalence study or not.

Abstract

Methods should be written in more detail about the study design, sampling, and clinical manifestation.

Introduction

1. The introduction needs to be improved by adding some information about the global prevalence, mortality, morbidity, and burden of HAdV both worldwide and in China.

2. Page 4, line 75: “Here we conduct a systematic review of all published research...” isn't that a systematic review and meta-analysis?

Methods

1. Page 5, line 109: Part 6 of the exclusion criteria says “Study period beyond the duration 2009-2020” while the authors indicated data extraction was conducted between Jan 2009 and Mar 2021. Also, in Appendix1 study period is 2009-2021 but in table S3 it is from 2009 to 2020. Please explain the difference.

2. In appendix1 figure S1, I can't see the distribution of adenovirus typing pie chart for southwest China on the map!

3. There is not enough information about how the quality assessment was done! Please state the exact method that has been used, provide a complete checklist of risk of bias as an appendix, and address the references.

4. Page 6, lines 131-133: “an outbreak event was defined...” is there any reference for this definition?

5. Please report sensitivity and specificity of laboratory determination methods that have been used.

Reviewer #2: The hypothesis and objectives of the work are clearly stated.

The selection of the articles is carried out properly.

Statistical analyzes are adequate.

Reviewer #3: The study is a systematic review and meta-analysis about human adenovirus (HAdV) infection associated with respiratory disease in China. The methodology is in accordance with a systematic review and met analysis article.

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Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: Results

There could have been data from HAdV vaccination in China among all age groups and a proper comparison of HAdV incidence between vaccinated and non-vaccinated individuals.

There could have been information about the most common type of HAdV separated by year from fig2B and fig2C.

Reviewer #2: The results section describes very well the analysis carried out considering three different age ranges, and important to describe.

The graphs are well designed and display the results in an easy to view manner.

The comparative table is correct and presents valuable information comparing outbreaks and surveillance.

Reviewer #3: A total of 5056 studies were identified, of which 950 articles met the inclusion criteria and were analyzed in the study. The study analyzed both articles from outbreak studies as well as from surveillance studies.

Presentations of results could be improved, especially concerning use of expressions and words not well explained in the text, grammar errors that make the text hard to understand, including in Figure legends.

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Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: Discussion

Page 17 line 3: “The prevalent typing varies...” presented common HAdV types in the United States from 2003-2016. It would be better if authors used the same time period for comparison as the current study. And please mention the most common types globally not just one country like the USA.

Reference

Please add journal issue after volume number.

Reference order could have been reported by year, but it looks fine this way.

Minor issues

There is no line number after page 10.

Page 11, first paragraph line 5: rat � rate

Reviewer #2: The discussion is correct, with updated bibliography.

The results support the discussion and the conclusion reached by the authors.

The limitations of the study are clearly stated in the discussion.

Reviewer #3: The study discusses the analyses performed and its findings, comparing with studies from some other countries. I suggest including a discussion about mortality associated with HAdV infection, comparing findings of the study (0.03 mortality) with other studies, for example the study by Pscheidt et al. (2020 - https://doi.org/10.1002/rmv.2189) that found 3% fatalities among patients hospitalized with severe respiratory infection and who were HAdV-positive.

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Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: (No Response)

Reviewer #2: I recommend the acceptance of the evaluated work.

Reviewer #3: (No Response)

--------------------

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: The manuscript “Human infection with respiratory adenovirus in China: a systematic review and meta-analysis” is a review of 950 articles that describes Human adenovirus (HAdV) prevalence, predominant types, clinical manifestation among different age groups and settings, national wide. The objective is interesting, although it needs some revisions before acceptance.

Reviewer #2: The manuscript entitled “Human infection with respiratory adenovirus in China: a systematic review and metaanalysis”, authored by Mei-Chen Liu et al, described the epidemiological and clinical features of HAdV infections in China, from January 2009 to March 2021. In addition, the genetic and epidemiological characteristics of HAdVs were investigated.

I want to emphasize that the work is very well written and concisely covers all the epidemiological characteristics of HAdV respiratory infections.

The work carried out is a very important contribution to the knowledge of the classical and molecular epidemiology of HAdV in China and also provides valuable information worldwide.

Reviewer #3: The study is interesting and is worth publication, however thorough English revision is necessary. I recommend revision by a native English speaker.

Main comments and corrections were made in the pdf file, attached.

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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

Reviewer #3: No

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Attachments

Attachment

Submitted filename: PNTD-D-22-01337_reviewer_revised.pdf

Dear Dr Fang,

Thank you very much for submitting your manuscript "Prevalence of human infection with respiratory adenovirus in China: a systematic review and meta-analysis" for consideration at PLOS Neglected Tropical Diseases. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. The reviewers appreciated the attention to an important topic. Based on the reviews, we are likely to accept this manuscript for publication, providing that you modify the manuscript according to the review recommendations.

Please prepare and submit your revised manuscript within 30 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to all review comments, and a description of the changes you have made in the manuscript.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Thank you again for your submission to our journal. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Ali Rostami

Academic Editor

PLOS Neglected Tropical Diseases

Elvina Viennet

Section Editor

PLOS Neglected Tropical Diseases

***********************

Reviewer's Responses to Questions

Key Review Criteria Required for Acceptance?

As you describe the new analyses required for acceptance, please consider the following:

Methods

-Are the objectives of the study clearly articulated with a clear testable hypothesis stated?

-Is the study design appropriate to address the stated objectives?

-Is the population clearly described and appropriate for the hypothesis being tested?

-Is the sample size sufficient to ensure adequate power to address the hypothesis being tested?

-Were correct statistical analysis used to support conclusions?

-Are there concerns about ethical or regulatory requirements being met?

Reviewer #1: (No Response)

Reviewer #2: The objectives and design of the study are clear.

The statistical analysis performed was adequate.

Reviewer #3: Adequate.

--------------------

Results

-Does the analysis presented match the analysis plan?

-Are the results clearly and completely presented?

-Are the figures (Tables, Images) of sufficient quality for clarity?

Reviewer #1: (No Response)

Reviewer #2: The results are clear and correctly presented, as are the tables and figures.

Reviewer #3: Adequate.

--------------------

Conclusions

-Are the conclusions supported by the data presented?

-Are the limitations of analysis clearly described?

-Do the authors discuss how these data can be helpful to advance our understanding of the topic under study?

-Is public health relevance addressed?

Reviewer #1: (No Response)

Reviewer #2: The conclusions are supported by the results.

Study limitations are presented.

Reviewer #3: Adequate.

--------------------

Editorial and Data Presentation Modifications?

Use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. If the only modifications needed are minor and/or editorial, you may wish to recommend “Minor Revision” or “Accept”.

Reviewer #1: (No Response)

Reviewer #2: Accept

Reviewer #3: Accept after minor corrections.

--------------------

Summary and General Comments

Use this section to provide overall comments, discuss strengths/weaknesses of the study, novelty, significance, general execution and scholarship. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. If requesting major revision, please articulate the new experiments that are needed.

Reviewer #1: (No Response)

Reviewer #2: The manuscript entitled “Human infection with respiratory adenovirus in China: a systematic review and meta-analysis”, authored by Mei-Chen Liu et al, described the epidemiological and clinical features of HAdV infections in China, from January 2009 to March 2021. In addition, the genetic and epidemiological characteristics of HAdVs were investigated.

I want to emphasize that the work is very well written and concisely covers all the epidemiological characteristics of HAdV respiratory infections.

The work carried out is a very important contribution to the knowledge of the classical and molecular epidemiology of HAdV in China and also provides valuable information worldwide.

Reviewer #3: The authors made changes to the manuscript to address the reviewers' comments. A few corrections are still necessary before publication, as pointed in the pdf file (attached).

--------------------

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

Reviewer #3: No

Figure Files:

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org.

Data Requirements:

Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

References

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article's retracted status in the References list and also include a citation and full reference for the retraction notice.

Attachments

Attachment

Submitted filename: PNTD-D-22-01337_R1_reviewer_revised.pdf

Dear Dr Fang,

We are pleased to inform you that your manuscript 'Prevalence of human infection with respiratory adenovirus in China: a systematic review and meta-analysis' has been provisionally accepted for publication in PLOS Neglected Tropical Diseases.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Neglected Tropical Diseases.

Best regards,

Ali Rostami

Academic Editor

PLOS Neglected Tropical Diseases

Elvina Viennet

Section Editor

PLOS Neglected Tropical Diseases

***********************************************************