PONE-D-21-14064

Modeling non-pharmaceutical interventions in the COVID-19 pandemic with survey-based simulations

PLOS ONE

Dear Dr. Kaffai,

Thank you for submitting your manuscript to PLOS ONE. Your paper has been carefully reviewed and was considered positively, overall. However, some aspects need further consideration and should be integrated with additional content. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

In particular, two are the aspects that need particular attention:

1. Model description: Reviewer #3 has noted that the model should be described more precisely and with further details in order to be completely clear to the reader. We invite authors to expand the description.
2. Figure explanation and discussion: All reviewers have noted that figures are not completely clear, either in the discussion or in the caption. We invite authors to revise all figures, their captions, and the discussion of their content according to the comments of all reviewers.
3. References: Pay specific attention to the following Journal Requirements, pointing to a possible problem with references to retracted articles. References should be carefully checked before resubmission, each one should have a clear rationale for being cited. All changes in the references should be reported in the rebuttal letter to inform the reviewers. 

Minor comments have been also provided and require attention as well.

Overall, the paper has merits and is close to the quality needed for publication, which justifies the minor revision status. This however does not imply that the revision could be limited to few superficial fixes. All comments raised by the reviewers and the journal's editors should be specifically addressed, each one needs a comment explaining how the authors decided to proceed, and edits in the manuscript should be appropriate to the comment raised.  

Please submit your revised manuscript by Sep 26 2021 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: http://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,

Marco Cremonini, Ph.D.

University of Milan

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. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

"Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

3. Please note that in order to use the direct billing option the corresponding author must be affiliated with the chosen institute. Please either amend your manuscript to change the affiliation or corresponding author, or email us at plosone@plos.org with a request to remove this option.

4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ.

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 (if provided):

[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: Yes

Reviewer #3: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: N/A

**********

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: In this manuscript, the authors model the effects of non-pharmaceutical interventions to investigate the spread of COVID-19 for some states in Germany, using an agent-based model with a heterogeneous population based on survey data from the German Socio-Economic Panel. From the results of the simulations, they found that some scenarios, as quarantine and home-office, are the most effective measures to reduce COVID-19 cases. They also investigate and evaluate the effect of some NPIs on the number of COVID-19 cases in the risk group (age > 60 years). The research is interesting and presents a model that can be useful to assist in decision-making regarding COVID-19, a current health problem of great concern. The manuscript is well written, the methodology is sufficiently detailed and, the conclusions are supported by the results found. I consider that the article is scientifically sound and suitable for publication in PLOS ONE. I have a few comments nonetheless:

1. It is clear from the text that Figure 1 is the cumulative number of COVID-19 cases, but maybe the authors can make this clear in the caption or y-axis of the figure to avoid doubts. Does Figure 2 represent accumulated cases as well?

2. Perhaps the authors can explore the results of Figure 4 a little further. Are the differences in the behavior of the curves in the four states linked to demographic variation? Could the finding "the scenarios in which schools re-open and pre-pandemic home office rates are attained lead to the lowest proportion among the elderly risk-group" be influenced by the fact that the model does not consider contacts with relatives or friends (as children transmitting to their grandparents, for example)? (I understand that this would be reduced in the case of severe isolation measures, but it is an important point if the model is used in places where children live or stay with older relatives, as in some underdeveloped countries).

3. In the caption of Figure 4, the title says "Number of infected agents" while the legend says "share of cases". I suggest that authors standardize the name so that "number" is not confused with the absolute number. Also, perhaps the authors could consider presenting the percentages infected for each age group, not only for >=60 (maybe in a supplementary table with the final infected number or percentage), but this is just a suggestion.

4. Perhaps the authors might consider changing the yellow color in Figs 2 and 4, which can be difficult to see depending on the readers’ screen.

5. On page 6, line 302, if I am not mistaken, it seems like “Figures 5-9 in SI” means Figures S1-S5.

Reviewer #2: In this paper, “Modeling non-pharmaceutical interventions in the COVID-19 pandemic with survey-based simulations”, the authors aim to develop an agent-based model concerning the “what-if” fundamental question in implementing the NPIs’ during the COVID-19 pandemic.

The topic is interesting and the document is well presented. While the results trends are illustrative enough in the figures, I suggest to add a table which contains the standard deviation, mean and CI for each intervention removal's configuration. These tables, particularly for figure 3 and 4, make the comparison among baseline and other configurations more clear.

From my point of view the submitted paper is suitable for publication in PLOS ONE in the presented form.

Reviewer #3: The paper presents an application of the Agent-based modeling approach to study the efficacy of Non-pharmaceutical interventions (NPIs) following the outbreak of Covid-19. The authors consider a basic SEIR model and couple it with survey data to build a model where they can effectively track and modify the daily routines of the agents.

The approach adopted in the paper is novel and is a promising avenue of further research in agent-based models. While agent-based models have had success as diagnostic tools and have been able to provide great insight into many systems of interest, convincing applications that integrate real-world micro-level data have been few and far between. By basing their model on data from surveys on the behavior and routines of the people from 4 provinces of Germany, the paper is extremely important towards ABMs becoming more widespread as a modeling paradigm.

Having said that, the paper in question does suffer from a certain number of deficiencies, which undermine the message and the importance of the work. Let me begin by some general comments before providing specific comments:

1. A major shortcoming of the paper is that it isn't clear what the model actually is. Care should be taken to provide a detailed schematic of the various parts of the dynamical model and the different sections of the population considered along with a more detailed description of the NPIs.

2. Furthermore, reading the figures is a bit difficult since the baseline scenario is not the baseline "no-intervention" scenario (as one would intuitively expect) but with all NPIs in place. it could be better to relabel the individual curves so that "no-quarantine" becomes the baseline "no-intervention" scenario.

3. The authors provide a link to the repository where the code for the model is available. While laudable, it is difficult to know where and how to begin using the code since a complete Readme file has not been provided. Given the ever-growing importance of computer simulations, especially in ABMs, it is important that end-users be provided with all the necessary information to be able to run and explore the results of the model. Since the computer code is an integral part of the research underlying this paper, it is important that the authors take the time to address this point.

Moving on to specifics:

1. Lines 193-194: Are there any parameter configurations, other than those presented in the paper that lead to similar results? If so, how dissimilar are these parameter configurations as compared to those presented in the paper?

2. Line 218: What economic sectors are the authors referring to here?

3. Line 219: There seems to be an apparent contradiction here: While establishing home office worker proportions to pre-pandemic times leads to a marked increase in the number of cases, it is strange to see that people working "normal hours" (and thus presuambly going to work) doesn't increase case numbers. Why is this the case?

4. Fig 4: Why is it that the "no quarantine" scenario also leads to the share of cases in the "at-risk" population to reach levels similar to those of "open schools" and "normal home office"?

5. Fig 4: Caption in the body of the paper reads "Number of infected agents" while the figure itself plots the "share of the at-risk population".

Finally, at many points in the paper, the authors state the results of the simulations without providing any explanation as to what the probable causes could be. These are detailed below:

1. Line 216: Why is it the case that quarantine is a less important NPI in the two smaller states?

2. Lines 228-229: The authors write that the consequences of opening up all educational institutions are very different than if only one type of educational institution is opened? Why is this the case? Perhaps the survey data should be able to throw some light on the question.

3. Line 247: Why is it the case that the opening up of universities seems to play only a small role in the total number of cases?

A few typographical errors

1. In the abstract, line number 5 "researcher" should read "researchers".

2. Line 12: "decision-maker" should read "decision-makers".

3. Every instance when a quotation mark has been used must be corrected, for instance in lines 35 and 85.

**********

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

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.

Modeling non-pharmaceutical interventions in the COVID-19 pandemic with survey-based simulations

PONE-D-21-14064R1

Dear Dr. Kaffai,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Marco Cremonini, Ph.D.

University of Milan, Italy

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: