Dear Ms Nguyen,

Thank you very much for submitting your manuscript "Hybrid simulation modelling networks of heterogeneous care homes and the inter-facility spread of covid-19 by sharing staff" 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,

Claudio José Struchiner, M.D., Sc.D.

Associate Editor

PLOS Computational Biology

Virginia Pitzer

Deputy Editor-in-Chief

PLOS Computational Biology

***********************

Reviewer's Responses to Questions

Comments to the Authors:

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

Reviewer #1: This paper develops a model of the spread of covid infections in care homes and it explores a number of relevant scenarios related to staffing, with particular interest to the use of bank staff. This is a topical issue with the potential to inform decisions in staffing of care homes and it is worthy of publication. The paper is well designed and written and the models well implemented. Some suggestions for further improvement are listed below:

1. The paper discusses the use of hybrid simulation in the introduction. At this point the justification of using a hybrid model does not work very well. It refers to the use of hybrid modelling, but it is not clear for the reader why hybrid simulation is suitable. It would be better if the authors explain in the introduction the problem and the key aspect that the model needs to represent. The justification of the use of hybrid modelling could be discussed in the materials and methods section.

2. It seems like the problem is the lack of staff in care homes, which is only indirectly referred to in the paper. It would be useful to make this clearer from the beginning and in the abstract also.

3. What is the aim of the model? It would be useful to include in the methods section the aim and questions that the model aims to answer.

4. Results section - Impact of different usage levels of bank/agency staff. It would be useful to indicate whether there is a statistically significant difference in the RR of infection or outbreak between the different scenarios tested.

5. There are two sections on validation - Confidence building (Verification and validation) and Validation results. Consider merging.

6. There are some typos in the manuscript that need attention. For example line 80 – understaffed instead of understaffing. Please check the manuscript carefully.

Overall, i think this is very interesting work and worthy of publications. I look forward to seeing the revised manuscript.

Reviewer #2: This is a rather comprehensive study with complex modelling consideration on the disease transmission in a heterogeneously mixed system. I have the following concerns. The major one is that this manuscript seems to lack a real-world dataset to support the modelling outcomes.

. in table S1-5, the F*xi term in the transmission path seems strange to me. what is the meaning of (1 - F*xi)? And what is the intuition behind this term? Besides, it seems the physical unit does not hold consistently. The unit of all ‘flow’ should be ‘# of individuals’, right?

. should it be normal (0,1)? Normal(1,0) means just constant 1.

. is there any fitting conducted in this study? If yes, how is the fitting conducted? So far, I did not see the fitting results.

. please discuss the limitations of this study.

Reviewer #3: Please see the attachment.

Reviewer #4: See attached.

**********

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: Yes

Reviewer #2: No: I did not find code or data open-accessed.

Reviewer #3: Yes

Reviewer #4: No: Most of the simulations are conducted in a packed software AnyLogic so it's hard to verify the results, though the authors share the setting of the model.

**********

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

Reviewer #3: No

Reviewer #4: 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.

Data Requirements:

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: Review Report.pdf

Attachment

Submitted filename: Review_Reports___PCOMPBIOL_D_21_01703.pdf

Dear Ms Nguyen,

We are pleased to inform you that your manuscript 'Hybrid simulation modelling networks of heterogeneous care homes and the inter-facility spread of covid-19 by sharing staff' 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,

Claudio José Struchiner, M.D., Sc.D.

Associate Editor

PLOS Computational Biology

Virginia Pitzer

Deputy Editor-in-Chief

PLOS Computational Biology

***********************************************************

Reviewer's Responses to Questions

Comments to the Authors:

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

Reviewer #4: The authors addressed all my concerns well, and I recommend the manuscript for publication.

**********

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 #4: No: 

**********

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 #4: No