PONE-D-24-49578Clinical evolution and medical resource utilization in adult patients with respiratory syncytial virus infection at a community hospital in ArgentinaPLOS ONE

Dear Dr. Bengolea,

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 Feb 22 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,

André Ricardo Ribas Freitas

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.  Thank you for stating the following financial disclosure:

“The research described herein was supported by Pfizer Inc. LRA, CGV, and NZ are

employed by Pfizer Argentina SRL. AB is an employee of Hospital Alemán, which

received financial support from Pfizer Inc. for this study (including manuscript

preparation).”

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

3. We noted in your submission details that a portion of your manuscript may have been presented or published elsewhere. [A poster presenting preliminary results from this study is scheduled for presentation at the upcoming ISPOR Europe conference in Barcelona. The data and analyses in this manuscript encompass a comprehensive, final dataset with additional insights and detailed analyses that go beyond the scope of the poster. Accordingly, this submission does not constitute dual publication, as it provides an expanded and complete version of the findings.] Please clarify whether this [conference proceeding or publication] was peer-reviewed and formally published. If this work was previously peer-reviewed and published, in the cover letter please provide the reason that this work does not constitute dual publication and should be included in the current manuscript.

4. In this instance it seems there may be acceptable restrictions in place that prevent the public sharing of your minimal data. However, in line with our goal of ensuring long-term data availability to all interested researchers, PLOS’ Data Policy states that authors cannot be the sole named individuals responsible for ensuring data access (http://journals.plos.org/plosone/s/data-availability#loc-acceptable-data-sharing-methods).

Data requests to a non-author institutional point of contact, such as a data access or ethics committee, helps guarantee long term stability and availability of data. Providing interested researchers with a durable point of contact ensures data will be accessible even if an author changes email addresses, institutions, or becomes unavailable to answer requests.

Before we proceed with your manuscript, please also provide non-author contact information (phone/email/hyperlink) for a data access committee, ethics committee, or other institutional body to which data requests may be sent. If no institutional body is available to respond to requests for your minimal data, please consider if there any institutional representatives who did not collaborate in the study, and are not listed as authors on the manuscript, who would be able to hold the data and respond to external requests for data access? If so, please provide their contact information (i.e., email address). Please also provide details on how you will ensure persistent or long-term data storage and availability.

5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information .

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.

Additional Editor Comments:

Dear Dr. Agustin Bengolea,

Thank you for submitting your manuscript titled "Clinical evolution and medical resource utilization in adult patients with respiratory syncytial virus infection at a community hospital in Argentina" to PLOS ONE.

After review by three experts, all have recommended minor revisions. We appreciate the significant contribution of your work and kindly request that you prepare a revised version addressing the reviewers' comments and suggestions. Please include a detailed response letter explaining how each point has been addressed.

If you require any clarification during the revision process, feel free to reach out to me for assistance.

Best regards,

André Ricardo Ribas Freitas

Academic Editor

PLOS ONE

[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: Partly

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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: This article presents data on the RSV burden in adults from a single center in Argentina. Although it adds little to the existing body of evidence on the topic, it is well-written.

A few minor comments.

Table 1: add the % of patients with at least one chronic condition

For influenza patients: Add the % of CTC and ATB use. Add if available % of flu vaccination.

Would it be possible to add information on co-infections for the RSV patients?

I am surprised by the high rate of Antibiotic prescriptions in these patients. (Is this due to bacterial co-infection? Or misuse ?) Can you comment on this rate and the high CTC rate as well?

Reviewer #2: The authors describe differences between the two cohorts (syncytial virus and influenza) and conclude with some differences between them. ¿Are those differences significant? ¿It would be appropriate to explain why a statistical study was not carried out between the two cohorts?.

The authors report that 27 patients required ICUs; nineteen received NIV and 8 received mechanical ventilation. Then, they say that 31 patients met the criterion of "severe disease", which includes the compound of non-invasive ventilation and admission to the ICU. Why that difference of 4 patients?

Reviewer #3: This is an important study on RSV in Argentina, for which there is little published evidence, especially regarding the burden of disease among adults and the healthcare utilization.

The authors conducted a retrospective cohort study for which they identified all RSV positive cases in a 14 year period in a single Argentinian center. They also report the number of all patients that were subjected to viral testing. The manuscript is well structured and written and with an easy to follow, logical chain of thoughts. I will give comments in chronological order and will highlight aspects that I deem critical that should be revised to improve the quality of the work.

Of note, the study was financially supported by Pfizer, and three of the authors are employed by the company.

1. Title: no comments

2. Abstract: I think the finding that 75% were treated with antibiotics is absolutely worrying. This should be picked up in the conclusions section as well, depending on further investigations/analyses that I comment on in the results part.

3. Introduction: no comments

4. Methods: please briefly explain what the algorithm is for microbiological/viral testing, as the overall number that you report in the results for such a long period of time is rather low (212 per year?)

5. Results: please provide numbers also per year, so potential time trends, both with regard to total tests ordered and positive tests, can be assessed

6. Results: I think one crucial information that is lacking at the moment is information on the reasoning of antibiotic treatment. It could be helpful to include data on microbiological diagnostics in these cases (they are not that many, so it should be feasible), to approximate whether there is a reasonable number of patients with a bacterial co-infection. I presume that anyhow the vast majority will be unneccesary overtreatment of viral cases.

7. Discussion: The issue of overtreatment could be picked up even more here

**********

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:  Paul Loubet

Reviewer #2: No

Reviewer #3: 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.

PONE-D-24-49578R1Clinical evolution and medical resource utilization in adult patients with respiratory syncytial virus infection at a community hospital in ArgentinaPLOS ONE

Dear Dr. Bengolea,

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 15 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,

André Ricardo Ribas Freitas

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 :

Dear Dr. Bengolea,

Thank you for your revised submission of the manuscript titled "Clinical evolution and medical resource utilization in adult patients with respiratory syncytial virus infection at a community hospital in Argentina" (Manuscript ID: PONE-D-24-49578R1).

After reviewing the updated version and considering the feedback from both reviewers, I recommend that you proceed with a minor revision. The reviewers noted that you have addressed the majority of the concerns raised previously. However, two points still require your attention:

Table 2 – Please clarify the number of patients requiring NIV, ensuring consistency with your response and providing the adjusted mean days accordingly (Reviewer 2).

Antibiotic use – Reviewer 3 suggested further contextualization of the observed antibiotic use rate, including a comparison with other studies, and also flagged a phrase that should be clarified ("a predominantly viral pathogen").

Please revise the manuscript accordingly and submit a point-by-point response to the reviewers’ comments.

We look forward to receiving your revised manuscript.

Best regards,

André Ricardo Ribas Freitas

Academic Editor

PLOS ONE

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

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

Reviewer #3: (No Response)

**********

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

Reviewer #3: Yes

**********

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

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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: In Table2, the number of patients recquired NIV were 19, but in your response 4 received NIV out of the ICU

Thus ,the number of NIV in Table 2 must be 23 , with adjusted mean days (SD)

Reviewer #3: Thank you for addressing most of my concerns.

One remaining issue is the antibiotic overtreatment. I think it still lacks contextualization. Is the rate observed in your cohort high, low or average? can you cite some studies for a better comparison?

Furthermore, what do you mean with "a predominantly viral pathogen"??? RSV is a virus, period.

**********

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

Reviewer #3: 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.

Clinical evolution and medical resource utilization in adult patients with respiratory syncytial virus infection at a community hospital in Argentina

PONE-D-24-49578R2

Dear Dr. Bengolea,

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,

André Ricardo Ribas Freitas

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Dear Dr. Bengolea and colleagues,

Thank you for submitting the revised version of your manuscript entitled “Clinical evolution and medical resource utilization in adult patients with respiratory syncytial virus infection at a community hospital in Argentina” (Manuscript ID: PONE-D-24-49578R2).

I have reviewed your responses to the reviewers' comments and the updated manuscript. I am pleased to inform you that your revisions have successfully addressed all remaining concerns, and I am happy to accept your manuscript for publication in PLOS ONE.

Congratulations on your important contribution. Your work adds valuable insights into the clinical burden and healthcare impact of RSV infections in adults in real-world settings, and I believe it will be of interest to many readers.

I wish you all the best with the final steps of publication and in your ongoing research.

Warm regards,

André Ricardo Ribas Freitas, MD, PhD

Academic Editor, PLOS ONE

Reviewers' comments: