PONE-D-24-60482Diagnostic accuracy evaluation of a point-of-care antigen test for SARS-CoV-2 and influenza in UK primary care (RAPTOR-C19)PLOS ONE

Dear Dr. Tonner,

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 09 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,

Bushra Akhtar, Ph.D

Academic Editor

PLOS ONE

Journal Requirements:

1. When submitting your revision, we need you to address these additional requirements. 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. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.  When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 3. Thank you for stating the following financial disclosure: University of Oxford Medical Sciences Division Benefactors Urgent COVID-19 Fund [COVID-19 Research Response Fund Grant 0009325] to BDN, FDRH, JJL, TRF, PJT, GNH, MZ; National Institute for Health and Care Research (NIHR) School for Primary Care Research [SPCR grant 495] to BDN, FDRH, GNH, PJT, JJL, TRF; Urgent Public Health funding received by the CONDOR platform from the NIHR and Asthma + Lung UK [NIHR UPH grant COV0051] to BDN, PJT, GNH. PT, TRF, MG, UU, FDRH and GNH have received funding from the National Institute for Health and Care Research (NIHR) Community Healthcare MedTech and In Vitro Diagnostics Co-operative (MIC) (MIC 2016-018). PJT, TRF, MG, UU, BN and GNH currently receive funding from the NIHR HealthTech Research Centre (HRC) in Community Healthcare (NIHR205287) at Oxford Health NHS Foundation Trust. TRF and FDRH receive funding from the NIHR Applied Research Collaboration Oxford and Thames Valley at Oxford Health NHS Foundation Trust (NIHR200172). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Roche International Ltd provided consumables and site training free of charge, together with a grant to the University of Oxford to support the study.   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. 4. Thank you for stating the following in the Acknowledgments Section of your manuscript: We are grateful to all study participants, RAPTOR-C19 site staff, and the staff of the NIHR Clinical Research Network, Thames Valley and South Midlands for their support for the study. We would like to thank Micheal McKenna for RedCAP support, patients and practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre (RSC) who share pseudonymised data to support research and surveillance (UKHSA is the principal sponsor of the RSC); EMIS, TPP, Vision and Wellbeing for assistance with pseudonymised data extraction. Membership of the RAPTOR-C19 Study Group is as follows: Katie Arundell1, Gail N. Hayward1, F. D. Richard Hobbs, Heather Kenyon, Joseph J. Lee, Kathryn Lucas, Brian D. Nicholson, Jessica Smylie, Sharon Tonner, Philip J. Turner.Nuffield Department of Primary Care Health Sciences, University of Oxford, UKNIHR Clinical Research Network, Thames Valley and South Midlands, Oxford, UK We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: University of Oxford Medical Sciences Division Benefactors Urgent COVID-19 Fund [COVID-19 Research Response Fund Grant 0009325] to BDN, FDRH, JJL, TRF, PJT, GNH, MZ; National Institute for Health and Care Research (NIHR) School for Primary Care Research [SPCR grant 495] to BDN, FDRH, GNH, PJT, JJL, TRF; Urgent Public Health funding received by the CONDOR platform from the NIHR and Asthma + Lung UK [NIHR UPH grant COV0051] to BDN, PJT, GNH. PT, TRF, MG, UU, FDRH and GNH have received funding from the National Institute for Health and Care Research (NIHR) Community Healthcare MedTech and In Vitro Diagnostics Co-operative (MIC) (MIC 2016-018). PJT, TRF, MG, UU, BN and GNH currently receive funding from the NIHR HealthTech Research Centre (HRC) in Community Healthcare (NIHR205287) at Oxford Health NHS Foundation Trust. TRF and FDRH receive funding from the NIHR Applied Research Collaboration Oxford and Thames Valley at Oxford Health NHS Foundation Trust (NIHR200172). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Roche International Ltd provided consumables and site training free of charge, together with a grant to the University of Oxford to support the study. Please include your amended statements within your cover letter; we will change the online submission form on your behalf. 5. One of the noted authors is a group or consortium. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address. 6. 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.

[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: Partly

**********

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

Reviewer #1: 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

**********

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

**********

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:  In this manuscript authors have explored the diagnostic accuracy of a point-of-care antigen test for SARS-CoV-2 and influenza in primary care facilities. Overall, the study is well structured and data is nicely presented, however, few areas need improvement and clarification.

1. The POCT was conducted unilateral nasopharyngeal samples from participants while the reference test was conducted using combined swabs from nasal and oropharyngeal sites. How can these different methods of taking samples affect the test results? or can ensure a consistency in the method to compare these tests sensitivities? Previously, it has been reported in some studies that combined naso-oropharyngeal swab can be more sensitive as compared to nasopharyngeal swab (10.1080/23744235.2018.1546055, 10.1002/rmv.2106). So, it would be interesting to see if the samples for both tests are taken by the same procedure.

2. Check the values presented in the table 1 particularly for Previous COVID-19 infection (Positive antigen test reported) if the values are represented as number (%) as mentioned in the table heading.

**********

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: 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.

Diagnostic accuracy evaluation of a point-of-care antigen test for SARS-CoV-2 and influenza in UK primary care (RAPTOR-C19)

PONE-D-24-60482R1

Dear Dr. Tonner,

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,

Yury E Khudyakov, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: