Peer Review History

Original SubmissionOctober 4, 2024
Decision Letter - Raffaele Serra, Editor

PONE-D-24-39467Impact of prior SARS-CoV-2 infection on perioperative cardiac, pulmonary and neurocognitive complications in elderly patients: study protocol for an observative cohort studyPLOS ONE

Dear Dr. Saller,

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.

The manuscript is substantially well written, but some minor revisions are needed.

Please submit your revised manuscript by Dec 13 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,

Prof. Raffaele Serra, M.D., Ph.D

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 provide a complete Data Availability Statement in the submission form, ensuring you include all necessary access information or a reason for why you are unable to make your data freely accessible. If your research concerns only data provided within your submission, please write "All data are in the manuscript and/or supporting information files" as your Data Availability Statement.

3. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

4. Please include a caption for figure 1.

5. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Tables 1 and 2 in your text; if accepted, production will need this reference to link the reader to the Table.

6. 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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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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

**********

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: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The study titled "Impact of prior SARS-CoV-2 infection on perioperative cardiac, pulmonary, and neurocognitive complications in elderly patients" aims to investigate how previous SARS-CoV-2 infection affects the risk of perioperative complications in elderly patients undergoing elective surgeries. The study is important for Vulnerability of Elderly Patients, Long-term Impact of COVID-19, and Postoperative Delirium and Complications.

Overall, it addresses a critical gap in knowledge, focusing on how a prior SARS-CoV-2 infection affects surgical risks in a vulnerable population.

A minor question is about the duration. While the focus is on complications within the first five postoperative days, some complications might emerge later. Extending the follow-up period or adding a later check-in (e.g., at 30 days post-operation) could help identify delayed complications that are relevant to patient recovery.

Reviewer #2: The paper is very interesting in all parts and the methods are very interesting. There are some elements to improve: 1) the literature, in fact I suggest to include the following paper doi:10.2217/bmm-2020-0201.

2) it is necessary to improve the English.

**********

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

**********

[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.

Revision 1

Reviewer #1

Thank you for taking the time to thoroughly review our manuscript and for providing such constructive feedback.

Comment #1.1

The study titled "Impact of prior SARS-CoV-2 infection on perioperative cardiac, pulmonary, and neurocognitive complications in elderly patients" aims to investigate how previous SARS-CoV-2 infection affects the risk of perioperative complications in elderly patients undergoing elective surgeries. The study is important for Vulnerability of Elderly Patients, Long-term Impact of COVID-19, and Postoperative Delirium and Complications. Overall, it addresses a critical gap in knowledge, focusing on how a prior SARS-CoV-2 infection affects surgical risks in a vulnerable population.

A minor question is about the duration. While the focus is on complications within the first five postoperative days, some complications might emerge later. Extending the follow-up period or adding a later check-in (e.g., at 30 days post-operation) could help identify delayed complications that are relevant to patient recovery.

Thank you very much for this comment. The decision to focus on the first five postoperative days, rather than extending the observation period to 30 days, is based on evidence indicating that the majority of postoperative complications, particularly delirium, occur within this timeframe. According to studies, the risk of postoperative delirium is highest within the initial three to five days following surgery, especially among patients in critical care settings.

This approach allows for the efficient allocation of resources. Extending the observation period to 30 days would increase the logistical and operational demands significantly, while contributing limited additional value, as complications occurring later are less frequent and often unrelated to the immediate perioperative period. By focusing on this critical window, the study aims to capture the most clinically relevant data and ensure high-quality monitoring of early postoperative outcomes.

Reviewer #2

Thank you very much for your encouraging comments and constructive feedback on our manuscript.

Comment #2.1

The paper is very interesting in all parts and the methods are very interesting. There are some elements to improve: 1) the literature, in fact I suggest to include the following paper doi:10.2217/bmm-2020-0201.

Thank you for suggesting the publication "Cardiovascular Disease as a Biomarker for an Increased Risk of COVID-19 Infection and Related Poor Prognosis" as a potential source for the study protocol. The article provides valuable insights into the pathophysiological mechanisms linking cardiovascular disease and COVID-19, including the roles of ACE2, systemic inflammation, and coagulopathies. The study protocol primarily aims to investigate perioperative risks, such as postoperative delirium and pulmonary outcomes, in elderly patients with a history of SARS-CoV-2 infection. The publication does not address surgical or perioperative contexts, nor does it explore complications like delirium, which is a central focus of the study. That said, the publication is an extremely valuable resource, and I believe it would be highly relevant to incorporate it into the Discussion section of the study’s final publication. In that section, we plan to analyze the cardiovascular comorbidities of our participants and discuss their impact on the severity of COVID-19, its systemic effects on the body, and consequently, the incidence of perioperative complications. The article’s detailed discussion of the interplay between cardiovascular disease and COVID-19 outcomes would provide a strong foundation for interpreting and contextualizing our findings.

Comment #2.2

2) it is necessary to improve the English.

We appreciate your rating and we have made numerous changes to improve the language.

JOURNAL Requirements

Adaption to the PLOS-ONE style requirements

The style requirements of PLOS ONE are now fulfilled and changes have been marked in yellow as specified in an extra manuscript, which has been named `Revised Manuscript`.

Data Availability Statement

The required Data Availability Statement has been added and can be found on page 17.

Ethic Statement

Our ethics vote has now been added to the methods as requested.

Caption for figure 1

A heading has been added for figure 1. Figure 1 has also been mentioned under `Supporting Information` as requested.

References to table 1 and 2

In the texts, the tables that follow the section have now been addressed.

Reference List

The references have not been changed, only the order has been adjusted according to the specified template.

Decision Letter - Kiyan Heybati, Editor

PONE-D-24-39467R1Impact of prior SARS-CoV-2 infection on perioperative cardiac, pulmonary and neurocognitive complications in elderly patients: study protocol for an observative cohort studyPLOS ONE

Dear Dr. Saller,

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.

Thank you for taking the time to address the reviewer comments. In addition to the reviewer comment below, please address the following:

1) Methods - Please add reference to the STROBE checklist (https://www.strobe-statement.org/checklists/) and ensure the study is conducted according to this checklist to promote transparency and rigor.

2) Title - Please adjust ending to "study protocol for a case-control study" if this is accurate

3) Methods - Please discuss how COVID infection will be ascertained (i.e. asking patients versus laboratory evidence versus other)

4) Methods - Please discuss whether any propensity score matching or attempts of addressing confounders through adjustment will be conducted. These should ideally be included.

5) Please change the terminology of "elderly" to "older adults"

6) Please insert citations for the Numerical Rating Scale, PONV scales, and delirium (specify the tools in the actual Methods text)

Please submit your revised manuscript by Apr 10 2025 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,

Kiyan Heybati

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.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The aim of this study is to understand how a previous SARS-CoV-2 infection influences the occurrence of perioperative complications. The paper is interesting in all parts but I suggest to include the following paper: 10.2217/bmm-2020-0201

Finally, I suggest to revise the language including avoiding use of elderly and using older adults.

**********

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

**********

[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.

Revision 2

Reviewer #2

Thank you for taking the time to thoroughly review our manuscript and for providing such constructive feedback.

Comment #1.1

The aim of this study is to understand how a previous SARS-CoV-2 infection influences the occurrence of perioperative complications. The paper is interesting in all parts but I suggest to include the following paper: 10.2217/bmm-2020-0201

Finally, I suggest to revise the language including avoiding use of elderly and using older adults.

Thank you very much for this comment. We've addressed your concerns about the language and made the needed adjustments. We have taken note of your valuable reference to the study that identified cardiovascular disease as a biomarker for severe coronavirus 2019 (SARS-CoV-2) infection with related poor prognosis. We have taken note of this document with great interest and will be able to use this paper very well in the analysis and discussion in our following paper.

JOURNAL Requirements

Methods: add reference to the STROBE checklist

We have added a reference to STROBE-Checklist.

Title: add “study protocol for a case-control study”

This study follows a case-control design and is conducted both retrospectively and prospectively as a non-interventional observational study.

Methods: Discuss how COVID infection will be ascertained

We have now added to the methods that our patients are only questioned, and that no laboratory evidence of a past infection is required.

Methods: Discuss whether any propensity score matching or attempts of addressing confounders through adjustment will be conducted.

When analysing the data, we will use statistical methods to take confounders into account. We have added this note under Statistical analyses. The exact methods used will be listed in the corresponding paper in the analysis.

Terminology change

We changed the terminology of “elderly”.

Citations for Numerical Rating Scale, PONV scales and delirium and specify the tool in methods text

NRS for describing pain intensity can be found in the study design section. It also describes which number can be assigned to which degree of pain. We have added an appropriate citation.

The PONV score (Apfel-Score) has been added to the methods to show that it is used for risk classification of a patient preoperatively. The explanation of how the Apfel score is calculated has been expanded. A corresponding citation has been added, just as with the PONV-Intensity Scale.

The methods we use to screen for delirium are also shown in the method text below Table 2. For normal wards we use the 3D-CAM and the 4AT and in the ICU we also use the CAM-ICU. Citations are listed for all 3 instruments.

To remain in the correct order, the ranking of the citations has been adjusted.

Decision Letter - Kiyan Heybati, Editor

Impact of prior SARS-CoV-2 infection on perioperative cardiac, pulmonary and neurocognitive complications in older patients: study protocol for an observative case control study

PONE-D-24-39467R2

Dear Dr. Saller,

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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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,

Kiyan Heybati

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Kiyan Heybati, Editor

PONE-D-24-39467R2

PLOS ONE

Dear Dr. Saller,

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team.

At this stage, our production department will prepare your paper for publication. This includes ensuring the following:

* All references, tables, and figures are properly cited

* All relevant supporting information is included in the manuscript submission,

* There are no issues that prevent the paper from being properly typeset

You will receive further instructions from the production team, including instructions on how to review your proof when it is ready. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few days to review your paper and let you know the next and final steps.

Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

If we can help with anything else, please email us at customercare@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Kiyan Heybati

Academic Editor

PLOS ONE

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