Dear Miss Chen,

Thank you very much for submitting your manuscript "Features influencing the health and economic impact of long-acting antibody prophylaxis against COVID-19" for consideration at PLOS Computational Biology.

As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments.

We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation.

When you are ready to resubmit, please upload the following:

[1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

[2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file).

Important additional instructions are given below your reviewer comments.

Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts.

Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments.

Sincerely,

Joseph T. Wu

Academic Editor

PLOS Computational Biology

Virginia Pitzer

Section Editor

PLOS Computational Biology

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Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: This is a well written paper describing an interesting analysis.

AUTHOR SUMMARY

Please clarify whether shielding involves wearing a face mask and only going out when essential or if it is something else. I didn’t understand what shielding meant from this section.

INTRODUCTION

This is well written and does a good job of setting the scene for the analysis.

RESULTS

Fig 1a – suggest making the dots smaller and/or a lighter color so you can tell where multiple iterations stack on top of each other. y-axis appears to be wrong (incremental costs of ~$15m)

Lines 244-247 - I don’t think I follow what this sentence is saying

Fig 2 – Initially found this strange because the text on 2a and 2c isn’t mentioned until the paragraph beginning at line 280. Is it possible to shift the order around so that this is covered earlier?

fig 3d is hard to read. Suggest changing colors or making larger.

DISCUSSION

Does the paragraph in lines 373-378 relate at all to the study from South Korea mentioned in lines 316-331?

METHODS

Clearly state the perspective for the analysis. Lines 381=382 state that you’re taking the patient and the healthcare sector perspectives—do you mean two different perspectives or the societal perspective?

Since this is set in the UK, suggest using a discount rate of 3.5% in the base case to align with NICE recommendations.

Line 519 – Are you assuming that this drug would only be available in the private sector? What if it became available in the public sector?

Line 526-531 – could you provide further justification for these choices? Is it fair to assume that this is a linear relationship?

Do you include disutility for COVID or just for shielding? Where are the utilities for COVID illness?

SUPP

Table S3 – It would be helpful for the column headers to be explained

Reviewer #2: Review was uploaded as an attachment.

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Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: None

Reviewer #2: Yes

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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:  Angela Devine

Reviewer #2: No

Figure 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. 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 us at figures@plos.org.

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Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example in PLOS Biology see here: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5.

Reproducibility:

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Attachments

Attachment

Submitted filename: PCOMPBIOL-D-24-00735_reviewer_REVIEW.pdf

-->PCOMPBIOL-D-24-00735R1-->-->Features influencing the health and economic impact of long-acting antibody prophylaxis against COVID-19-->-->PLOS Computational Biology-->--> -->--> -->-->Dear Dr. Chen,-->--> -->-->Thank you for submitting your manuscript to PLOS Computational Biology. After careful consideration, we feel that it has merit but does not fully meet PLOS Computational Biology'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 within 30 days Jan 21 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 ploscompbiol@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pcompbiol/ 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 editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to formatting updates and technical items listed in the 'Journal Requirements' section below.-->--> -->-->* 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, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.-->-->We look forward to receiving your revised manuscript.-->-->Kind regards,-->--> -->-->Joseph T. Wu-->-->Academic Editor-->-->PLOS Computational Biology-->

Virginia Pitzer

Section Editor

PLOS Computational Biology

-->

Feilim Mac Gabhann

Editor-in-Chief

PLOS Computational Biology

Jason Papin

Editor-in-Chief

PLOS Computational Biology

-->

Journal Requirements:

1) Please upload all main figures as separate Figure files in .tif or .eps format. For more information about how to convert and format your figure files please see our guidelines:

https://journals.plos.org/ploscompbiol/s/figures

2) Please upload a copy of Figure Figure 5 which you refer to in your text on page 27. Or, if the figure is no longer to be included as part of the submission please remove all reference to it within the text.

3) Please amend your detailed Financial Disclosure statement. This is published with the article. It must therefore be completed in full sentences and contain the exact wording you wish to be published.

1) State the initials, alongside each funding source, of each author to receive each grant. For example: "This work was supported by the National Institutes of Health (####### to AM; ###### to CJ) and the National Science Foundation (###### to AM)."

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

If you did not receive any funding for this study, please simply state: u201cThe authors received no specific funding for this work.u201d

Reviewers' comments:

Reviewer's Responses to Questions

-->

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #1: The authors have addressed my comments

Reviewer #2: Thank you for the opportunity to review this updated manuscript. I have some further questions and comments:

1. The authors mention the NICE highly specialised technologies programme as a potential justification for using a £100,000 per QALY cost-effectiveness threshold. However, this programme is limited to very rare conditions with prevalence below 1 in 50,000 people and an eligible population of 300 – 500 people. From the INFORM study that has been used to guide the authors modelling assumptions, there are roughly 2 million people in England who met the immunocompromised definition. I continue to believe that this threshold does not provide a helpful indication of the potential cost-effectiveness of the proposed application of LAAB-PrEP in the England.

2. In response to my comment that the results presented did not appear to support the likelihood of LAAB-PrEP being cost-effective in the UK, the authors updated their definition of the “low-fatigue high-replacement” scenario so that his now appears to be cost-effective at £20,000 to £30,000 per QALY. I am somewhat uncomfortable with the scenario definition being amended to achieve a particular result. I think as a minimum it should be made clear in the methods that (some of) the scenarios have been selected in a purposeful way (i.e. to maximise the likelihood of a cost-effective outcome.)

3. Given the above, I wonder if the authors might consider presenting the main results in a more theoretical way e.g. by focussing on the multi-way scenario analysis of the key unknown parameters, to highlight how the interaction of these parameters influences potential cost-effectiveness (similar to the new S5 figure.)

4. Related to the above, for the PSA, I am not sure how useful it is to incorporate extremely wide uncertainty e.g. uniform [1/50, 1/5] for death risk, or uniform [0.1,0.9] for LAAB-PrEP into a single simulation. If many parameters are varied over a very wide range that is not informed by empirical data, then the proportion of samples that are cost-effective tell us little about the probability that the intervention will be cost-effective.

5. I was interested to see in figure S5, that the effectiveness of LAAB-PrEP has only a small impact on whether it’s use is cost-effective. This is presumably because the majority of the benefit is down to behaviour change (reduced disutility of shielding) and the direct protective effect against Covid-19 does not actually matter much. In extremis it would seem that much of the benefit could theoretically be achieve by placebo at no cost. In practice presumably individuals would not stop shielding without having good evidence of at least some effectiveness from LAAB-PrEP. Is there any empirical evidence on which the link between risk reduction and shielding behaviour that could be used to inform this link?

**********

Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: None

Reviewer #2: Yes

**********

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.]-->-->Figure resubmission: -->--> -->-->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. If there are other versions of figure files still present in your submission file inventory at resubmission, please replace them with the PACE-processed versions.-->-->Reproducibility: -->--> -->-->To enhance the reproducibility of your results, we recommend that authors of applicable studies deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols-->

PCOMPBIOL-D-24-00735R2

Features influencing the health and economic impact of preventing COVID-19 in immunocompromised individuals

PLOS Computational Biology

Dear Dr. Chen,

Thank you for submitting your manuscript to PLOS Computational Biology. After careful consideration, we feel that it has merit but does not fully meet PLOS Computational Biology'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 within 30 days Jun 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 ploscompbiol@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pcompbiol/ 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 editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. This file does not need to include responses to formatting updates and technical items listed in the 'Journal Requirements' section below.

* 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, competing interests statement, or data availability statement, please make these updates within the submission form at the time of resubmission. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

We look forward to receiving your revised manuscript.

Kind regards,

Joseph T. Wu

Academic Editor

PLOS Computational Biology

Virginia Pitzer

Editor-in-Chief

PLOS Computational Biology

Additional Editor Comments (if provided):

Journal Requirements:

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

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Authors:

Please note here if the review is uploaded as an attachment.

Reviewer #2: The authors have addressed the majority of my comments. There is one of my comments from the last review that the authors have not addressed or commented on.

1. In the previous review I wrote that

"The authors mention the NICE highly specialised technologies programme as a potential justification for using a £100,000 per QALY cost-effectiveness threshold. However, this programme is limited to very rare conditions with prevalence below 1 in 50,000 people and an eligible population of 300 – 500 people. From the INFORM study that has been used to guide the authors modelling assumptions, there are roughly 2 million people in England who met the immunocompromised definition. I continue to believe that this threshold does not provide a helpful indication of the potential cost-effectiveness of the proposed application of LAAB-PrEP in the England."

The authors have not addressed this in their response. In my opinion the best option would be to remove this threshold from the figures because for the general reader I think it creates a misleading impression of the likelihood of cost-effectiveness. However, if the authors wish the retain the use of this threshold then I suggest that my point above about the very small population that could potentially be eligible under this scheme is made explicit in both the main text and the figure captions where the threshold is presented.

**********

Have the authors made all data and (if applicable) computational code underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data and code 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 and code 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 or code —e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

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.]

Figure resubmission:

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. If there are other versions of figure files still present in your submission file inventory at resubmission, please replace them with the PACE-processed versions.

Reproducibility:

To enhance the reproducibility of your results, we recommend that authors of applicable studies deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Dear Dr. Chen,

We are pleased to inform you that your manuscript 'Features influencing the health and economic impact of preventing COVID-19 in immunocompromised individuals' has been provisionally accepted for publication in PLOS Computational Biology.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests.

Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated.

IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript.

Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS.

Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Computational Biology. 

Best regards,

Joseph T. Wu

Academic Editor

PLOS Computational Biology

Virginia Pitzer

Editor-in-Chief

PLOS Computational Biology

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