PONE-D-20-24487

Impact of vitamin D status and cathelicidin antimicrobial peptide on adults with active pulmonary TB globally: A systematic review and meta-analysis

PLOS ONE

Dear Dr. ACEN,

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.

Please submit your revised manuscript by May 02 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Jennifer A. Hirst, DPhil

Academic Editor

PLOS ONE

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When submitting your revision, we need you to address these additional requirements.

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2. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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- Please ensure you have included the full electronic search strategy for at least one database and uploaded it as an additional file.

Additional Editor Comments:

In addition to the comments there are a few other points that this manuscript needs before publication:

Please avoid abbreviations in the abstract (TB and LL-37)

Data should be plural (page 7 Data management and statistical analysis second line should read data from final studies were….) – please check through rest of manuscript

Please give justification for pooling SMD. Were Vitamin D and LL-37 measured using different units?

Results

Table 1:

• please reformat in landscape

• Define Nc, Please present as NC or Nc, currently both used

• Define PTB, PBMC

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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: This study of this systematic review and meta-analysis was carried out with rigor and achieved the objectives it set out to.

Although the existing studies have not allowed to find more consistent results, the systematic review and meta-analysis performed by the authors correctly follows the steps for carrying out these studies. Furthermore is relevant for clinical and biological areas.

Protocol was previously registered.

Participants, exposure, comparator and outcome (PECO) are clear. Also, eligibility criteria, quality of the studies, information sources, search strategy, data collection, risk of bias are also well explained in methods.

In what concerns meta-analysis, size variability, heterogeneity, methods and interpretation of results are all clear in the article.

However, minor reviews are suggested:

Aims

The title “Impact of vitamin D status and cathelicidinantimicrobial peptide on adults with active pulmonary TB globally: A systematic review and meta-analysis” does not reflect the objective regarding the relationship between Vitamin D status and cathelicidin levels on adults with active pulmonar TB.

(although it is the title of the protocol registered in PROSPERO)

Protocol aims: “The aim of this review is to determine the association of vitamin D status with cathelicidinexpression among adults with pulmonary disease.

Article Pag2. “The systematic review attempts to define the relationship between cathelicidin levels and vitamin D status in TB disease”

Article Pag4. “The objective of our systematic review was to compare vitamin D and LL-37 levels among TB patients to non-pulmonary TB (…) and to determine the association between vitamin D and LL-37 and any ….”

This last aim is clear and reflects the performed study so would suggest adjusting the previous ones.

Results:

There are two different types of studies, one is the determination of LL-37 plasma levels and the other is the cell expression of LL-37. It could be more explicit in the text. Also, for Vitamin D.

Pag 10. Table 1. Would suggest a reference in author column. It will help the readers find the article.

Pag 12. “The lowest vitamin D levels of >10ng/ml (…) six studies reported vitamin D deficiency levels of >20ng/ml”. This statement is not clear.

References

Suggest to review the references. Some are not complete (for example reference 8)

Reviewer #2: This study investigated the impact of vitamin D and LL-37 level on TB. The found that a significant difference was observed in both vitamin D and cathelicidin levels among TB patients and non-TB individuals (p= < 0.01). Overall, the study is interesting and the manuscript is well-designed. I just have several suggestions.

1. Please clarify which is the target of this study – TB or active pulmonary TB.

2. Please add some data in the abstract’s result section.

3. The introduction is too long.

4. Please add the level of Vit D and LL-37 and case number in TB and non-TB in the table 1.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-20-24487R1

Impact of vitamin D status and cathelicidin antimicrobial peptide on adults with active pulmonary TB globally: A systematic review and meta-analysis

PLOS ONE

Dear Dr. ACEN,

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.

Please clearly highlight the changes that were made to the manuscript to help the reviewers and Editor.​

Please submit your revised manuscript by Jun 17 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Jennifer A. Hirst, DPhil

Academic Editor

PLOS ONE

Journal Requirements:

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.

Additional Editor Comments (if provided):

Unfortunately I am unable to clearly see the changes you have made as requested by the reviewers. Please upload a revised version of the manuscript with the changes highlighted so it can be confirmed that the changes have been made.

Many thanks

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment 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. Registration is free. 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 PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Impact of vitamin D status and cathelicidin antimicrobial peptide on adults with active pulmonary TB globally: A systematic review and meta-analysis

PONE-D-20-24487R2

Dear Dr. ACEN,

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.

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Kind regards,

Jennifer A. Hirst, DPhil

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: