PONE-D-21-10679

Risk of hospitalization and mortality due to COVID-19 in people with obesity: An analysis of data from a Brazilian state

PLOS ONE

Dear Dr. Reis,

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 Aug 20 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

Additional Editor Comments:

Please change yellow to “other non-white ethnicity”

Change illiterate to no education

Typo – page 17 “Individuals who presented lang, heart, kidney diseases and diabetes” should read “Individuals who presented lung, heart, kidney diseases and diabetes”

Journal Requirements:

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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: No

Reviewer #2: No

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

Reviewer #1: No

Reviewer #2: No

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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: No

Reviewer #2: No

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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: The authors report on the association between hospitalization/death and an array of factors (demographics, comorbidity and symptoms/signs) for patients with COVID-19 as residents of Espiroto Santo Brazil.

General:

Please adhere to the STROBE guidelines for reporting of observational studies: https://www.equator-network.org/reporting-guidelines/strobe/

Introduction

1) Please explain why your study is needed. It seems that the question your study tries to answer is already answered.

2) Regarding the objective: “… this study aims to assess the risk of hospitalization and mortality

due to COVID-19 in people with obesity based on data from Espírito Santo residents, Brazil.”

The study methods and results imply a more wide approach. Please adjust the aims to be consistent with the rest of the manuscript.

Methods

3) How are patients includes in this database, what were the selection criteria? How many were eligible and how many were not included?

4) Describe methods of follow-up? How long was the follow-up?

5) How was race/ ethnicity determined? Self reported? Determined by physician? What do you mean by yellow ect?

6) Regarding death, there maybe patients remaining in hospital that have no yet reached an outcome (either death or discharged). This means there is a high risk of (non)-differential misclassification which could lead to bias.

7) Are the authors using a causal or a prognostic approach? Presently, the “adjusted model” is not suitable for causal interpretation nor is it adequately validated for use as a prognostic model. Please see also these references below:

doi: 10.1097/EDE.0000000000001258

DOI: 10.1097/EDE.0000000000001259

8) A such, there also seems to be a Table 2 fallacy problem with the analyses:

DOI: 10.1093/aje/kws412

Results

9) Please report, according to STROBE item 13: “numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow-up, and analysed” A flow diagram is highly recommended.

10) How many patients had missing data and how was this handled?

11) Why present OR when you can present RR?

12) Table 2-5: It would be helpful to add the number of patients to each table, e.g. n of x men were hospitalized and n of y women were hospitalized.

Discussion

13) The discussion could benefit from a thorough limitations section.

Reviewer #2: Dear Editor,

Cardioso dos Reis and colleagues performed a cross-sectional study attempting to assess predictors and risk factors for hospitalization and death among patients with obesity and COVID-19 in Brazil.

The study has very important data from underreported patient population; therefore, it deserves special attention. On the other hand, I have to mention that this manuscript needs a lot of work in several aspects including English language editing, clear description of the methods, and organized and consistent presentation of the results and findings.

Below you can see some comments.

Introduction

*I would make the introduction much shorter. In specific, I would remove the first three paragraphs since the general information provided there is well-known. I would start directly with risk factors/obesity.

Methods

*This section needs English language editing.

*Authors need to make sure they report all component of STROBE checklist.

*Inclusion and exclusion criteria can be defined more clearly.

*How was obesity defined? Did researchers rely on documentation or they used BMI or other tool?

Results

*This section needs English language editing, as well.

*Would change obese patients to patients with obesity

*Table 1: What is yellow color/race?

*Do the rest of the tables present univariate or multivariate associations? This should be clear in the text and the table notes.

*Why some variables were placed in the regression, while others were not?

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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.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-21-10679R1

Risk of hospitalization and mortality due to COVID-19 in people with obesity: An analysis of data from a Brazilian state

PLOS ONE

Dear Dr. Reis,

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 Oct 19 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:

Additional Editor Comments (if provided):

Please can the authors upload a marked-up version of the manuscript to allow reviewers to view changes that have been made from the previous version

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Reviewers' comments:

[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.

PONE-D-21-10679R2Risk of hospitalization and mortality due to COVID-19 in people with obesity: An analysis of data from a Brazilian statePLOS ONE

Dear Dr. Reis,

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 Jan 09 2022 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,

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):

Please make the following changes to use more inclusive terminology:

Yellow is still used to describe Asian populations in the flow chart. Yellow is not a race or ethnicity, please change.

Please replace "illiterate" used throughout the manuscript with "No education"

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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: (No Response)

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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: Partly

**********

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

Reviewer #1: 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

**********

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

**********

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 have addressed most of my comments. However, the following issues require attention:

Comment 1:

Regarding Previous comment and response 6 (see below), the people who were still under treatment and who were excluded could have a different risk of dying than the included people and they can have a different distribution of co-variates. Hence there is a high risk of differential misclassification especially considering the large proportion of patients that were excluded (49%): 59.698 of 118.138 people were included.

Previous comment and response 6:

Regarding death, there may be patients remaining in hospital that have no yet reached an outcome (either death or discharged). This means there is a high risk of (non)- differential misclassification which could lead to bias.

No. We selected for this study people confirmed for COVID-19 who had the evolution of

the disease closed as cure or death. People who were still undergoing treatment were

excluded.

Comment 2:

Previous comment 7 (see below) has not been addressed by the authors.

Previous comment 7:

Are the authors using a causal or a prognostic approach? Presently, the “adjusted model” is not suitable for causal interpretation nor is it adequately validated for use as a prognostic model. Please see also these references below:

doi: 10.1097/EDE.0000000000001258

DOI: 10.1097/EDE.0000000000001259

Comment 3:

Regarding previous comment and response 8, the potential Table 2 fallacy problem has not been addressed by the authors (see below).

Previous comment and response 8:

A such, there also seems to be a Table 2 fallacy problem with the analyses:

DOI: 10.1093/aje/kws412

The symptoms of runny nose, sore throat, diarrhea and headache showed counterintuitive

associations, possibly due to confounding variables not properly controlled, resulting in

statistically significant associations, giving the false idea of a "protective effect" for both

hospitalization and death due to COVID-19.

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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

[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.

Risk of hospitalization and mortality due to COVID-19 in people with obesity: An analysis of data from a Brazilian state

PONE-D-21-10679R3

Dear Dr. Reis,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Jennifer A. Hirst, DPhil

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: (No Response)

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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

**********

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

Reviewer #1: 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

**********

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

**********

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 have to be clear if the study is prognostic. For instance wording as “protective effect” suggests causality and should be avoided.

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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