PONE-D-24-03752Association between (ΔPaO2/FiO2)/PEEP and in-hospital mortality in patients with COVID-19 pneumonia: A secondary analysis

Short Title: (ΔPaO2/FiO2)/PEEP and in-hospital mortalityPLOS ONE

Dear Dr. Lin,

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.

==============================

ACADEMIC EDITOR: <ul><li>Thank you for your recent submission; your research paper has now been evaluated by two experts, and we have discovered significant information that can contribute to the scientific community. However, there are some issues that need to be corrected, so that we can reconsider your work further.

Please take the time to go over the reviewers' opinions, as well as their recommendations. Please respond to the points that have been brought up and handle the paper in the manner that has been advised.

Also please take care that

@ The aforementioned statistical points must be rectified and corrected.

@ Given the limitations mentioned, the conclusion should be rewritten in both abstract and at the end of the paper, also, mention that further randomized, well-designed trials should be conducted to investigate the findings in order to make generalized recommendations.==============================

Please submit your revised manuscript by May 01 2024 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: https://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,

Wael Hafez

Academic Editor

PLOS ONE

Journal requirements:

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

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please amend either the title on the online submission form (via Edit Submission) or the title in the manuscript so that they are identical.

3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please ensure that your ethics statement is included in your manuscript, as the ethics statement entered into the online submission form will not be published alongside your manuscript.

Additional Editor Comments:

Dear Authors:

Thank you for your recent submission.

Your research paper has now been evaluated by two experts, and we have discovered significant information that can contribute to the scientific community. However, there are some issues that need to be corrected so that we can reconsider your work further.

Please take the time to go over the reviewers' opinions as well as their recommendations. Please respond to the points that have been brought up and handle the paper in the manner that has been advised.

Also, please take care that .

The aforementioned statistical points must be rectified and corrected.

Given the limitations mentioned, the conclusion should be rewritten in both the abstract and at the end of the paper. It should also mention that further randomized, well-designed trials should be conducted to investigate the findings in order to make generalized recommendations.

[Note: HTML markup is below. Please do not edit.]

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

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

**********

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

**********

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: (ΔPaO2/FiO2)/PEEP seems to be a good predictor of outcome in patients with respiratory failure secondary to Covid-19. However, it is likely be a marker of disease severity rather than a modifiable risk factor. It is not clear from the manuscript what suggestions the authors have for clinicinas at bedside for modifying this risk factor. Was there any evidence in the data to suggest that the PEEP or FiO2 was not titrated appropriately?

Following gramattical/typographical errors for the consideration of the authors

Line 167, Most commom complications should probably read as most common comorbidities

Line 169 - 172, could be reformated to draw the attention of the reader to the limitations of PaO2/FiO2 ratio

Line 193 insufficiency are not known could read as insufficiency was not available in the primary dataset

Reviewer #2: I have gone through the study and have found some merit. But there are some suggestions and points which must be accommodated before the final acceptance of study.

1. The authors have presented Hazard Ratio in the results section of abstract with their confidence intervals but its missing p-value. p-value increases the worth of results. For each HR the associated p-value must be mentioned.

2.The conclusion section of abstract is unclear. What is meant by linearly associated? On what grounds the authors declared it linearly associated. It will be better if conclusion is general not specific about relationship.

3.In line 117,"Their mean age was 54.29 years, and 42 patients (21.0%) were female". This line should be separated into two lines explaining about mean age with SD. The numbers and associated percentages should be mentioned for both male and female.

4. From line 117-125, the authors discussed the significant difference but did not mention the p-values or any result with the statement supporting their outcomes. It will better if significant or non-significant results be mentioned with each statement

5.In whole study, authors some time used past tense and sometimes present tense. It should be adjusted for the complete study and should have same pattern for complete study. In discussion, authors used present tense while after few lines past tense were used. It should be checked properly.

6.The limitation of the study should be separated from the discussion section.

7. The conclusion section is short. it should be expanded and should discuss other aspects of study also like theoretical and practical implications.

8. In table 1, p-value should accompany the test-statistic value also.

9.The authors mentioned in their study that Continuous data were presented as mean ± standard deviation (SD) if normally distributed. Which variables were tested normal and which were non-normal. If all the variables were non-normal then this statement should be excluded. it would create confusion between normality and non-normality issue. the statement can be "Continuous data were presented as mean ± standard deviation (SD)".

**********

6. 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: Yes: Kesava Ananth Ramakrishnan

Reviewer #2: No

**********

[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.

Association between (ΔPaO2/FiO2)/PEEP and in-hospital mortality in patients with COVID-19 pneumonia: A secondary analysis

PONE-D-24-03752R1

Dear Dr. Lin,

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.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Wael Hafez

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Authors

good day

In light of your success in managing the paper as advised, we decided to approve the work based on the editor's and reviewers' comments, and it is now accepted. Congratulations!

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 #2: All comments have been addressed

**********

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 #2: Yes

**********

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

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 #2: Yes

**********

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 #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 #2: The authors have accommodated all the suggestions. have improved the analysis section and followed directions to improve the study.

**********

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 #2: No

**********