PONE-D-21-09294

Estimating the impact of interventions against COVID-19: from lockdown to vaccination

PLOS ONE

Dear Dr. Thompson,

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.

Based on the reviewers' comments, I recommend that you make substantial revisions to your manuscript. This should include improving the description of the model environment and how the agents interact in it. Please also be clear on how the sensitivity analysis was carried out and in reporting the outcome of this analysis. Then resubmit your improved version of the manuscript after making the revisions as advised in this letter.

Please submit your revised manuscript by Jun 19 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Martin Chtolongo Simuunza, PhD

Academic Editor

PLOS ONE

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[This project was funded by a grant from the COVID-19 Fast-Track program of the Fonds National de la Recherche Luxembourg (www.fnr.lu). The grant number is COVID-19/2020-2/14858807/ABMLUX, with the grant being awarded to Dr. J. Thompson. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.].   

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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

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

Reviewer #1: No

Reviewer #2: No

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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: No

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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

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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: The author presented a sophisticated, detailed agent-based model of Covid-19 transmission in Luxembourg. It evaluated a number of interventions to control the spread of Covid-19 in the community and compared the outcomes with other published models in the discussions. The study covered an important topic and included the verification and validation which help build confidence in the model. The inclusion of ODD protocol for the model help reading and understanding the model descriptions easier and more efficient and make it easier to replicate.

There are a number of issues that I would like the authors to clarify:

1. The paper discussed the sensitivity of the number of dead to the distribution of care homes, and the sensitivity of our model with respect to the probability of being asymptomatic and the transmission probability.

Which parameters is each model outcome sensitive to?

Which approach did the authors use to perform sensitivity analysis (e.g. univariate, multivariate, or probabilistic)?

I suggest the authors to include a table that summarizes the values of model parameters in the baseline scenario and the distributions used in sensitivity analysis.

2. How was the vaccine efficacy implemented in the model not very clear?

- Did the authors refer to the vaccine efficacy in this paper as efficacy against confirmed Covid-19 case or efficacy against transmission?

- What state variables of agents were affected if they are vaccinated? (Did the vaccinated agents have their state of infection changed from Susceptible to Recovered/Immune at the probability p1 and p2?)

- How did vaccination affect the transmission if susceptible vaccinated individuals come into contact with infected individuals and their disease progression if infected?

3. The number of simulations (ten) performed for each scenario seem quite small for a highly stochastic model like this model. I appreciate the extensive runtime for this high-resolution agent-based model. However, how did you decide that 10 simulations were sufficient to capture the true behaviours of the system? Would reducing the resolution and increasing the number of simulations produce outcomes with less uncertainty?

4. I appreciate that it is a very sophisticated and detailed model. However, would the purposes of the study be achieved with a simpler model such as a stochastic compartment model or an ABM with simpler structure? The authors mentioned that some of their results were similar to results from other studies which using simpler models. In this case, what would be the justification for building a more complex model?

Reviewer #2: The paper presents a detailed agent-based model that simulates COVID-19 pandemic dynamics over a small country, drawing very interesting results. The proposed system has agents with a high level of detail of the human interactions and routines, a great diversity of spatial locations and their intrinsic impacts, and it is very customizable. The methodology includes a consistent estimation of the parameters and used the classic SEIR model as a baseline, showing higher accurate inferential performance. However, some improvements must be made before its publishing.

The overall text is well written but sometimes exaggerates in length, and many paragraphs could be replaced by a diagram, a table, etc, reducing the length of the text and yet improving the readability of the results.

There is a problem with the location and quality of the images in the review text that harmed the reading and understanding of the text. All images appeared at the end of the text, which is inopportune. I suggest fixing this issue for the next review rounds.

In the State of Art section I think is missing a lot of recent machine learning and ABM models. This section can be improved with a deeper revision of recent research of agent-based epidemiological simulation of COVD19.

In the Methods section, the authors focused on the semantic meaning of the system components, which is perfectly understandable given the scope of the research. However, a little bit more details about the software implementation could improve the text and help the readers interested in implement or even employ the model. On the other hand, some descriptions of the model behavior (e. g. the school and classes descriptions) could be abbreviated.

Or you simply share the link of the source code or you should remove from the text the promise of opening the code in the future.

The authors let it clear in the text that the ABM has a network structure. But the Locations subsection gives the impression that the software is grid-oriented. How explicitly occur the relationships between the locations and the agents? How are they represented? Along with the text, the authors recovered the notion of a network model but in a fashion hard to understand. A good example is a car using by the agents. There will be a unique car location shared by all agents? I think that including a Network Diagram in this section, showing a small sample of the agents and their interactions will help the readers to understand better how your model works.

The ODD protocol in Appendix has an interesting high-level description of the whole system. However, I still miss some logical diagrams of the software structure and architecture (maybe a UML package diagram, or a component diagram ?)

In Model Evaluation and Validation, much of these paragraphs can be simplified or synthesized using mathematical formulas or replaced by a table with the parameters and their sources.

The results are very interesting but are spread in text and should be synthesized in a table, with the results of the proposed model and the SEIR model side by side, together with a statistical significance test of the difference between them.

Finally, I think this research is very interesting and opportune and their insights are very important and worth publishing after improving the paper.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-21-09294R1Estimating the impact of interventions against COVID-19: from lockdown to vaccinationPLOS ONE

Dear Dr. Thompson,

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.

The reviewers recommends that you make minor revisions to your manuscripts, including further  justification of the modelling method used . Please attend to all of them and resubmit the revised one as advised in this manuscript.

Please submit your revised manuscript by Dec 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: 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,

Martin Chtolongo Simuunza, PhD

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.

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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 #1: (No Response)

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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 #1: Yes

**********

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

Reviewer #1: 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 #1: 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 #1: 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 #1: Some further comments following the authors' responses:

1/ Regarding the vaccination efficacy, the authors only consider the all-or-nothing scenario that appears not to be the case for COVID-19 vaccines. Expermiments that consider the efficacy in terms of both infection and transmission would be more useful.

2/ I found the justification on the appropriateness of agent-based models compared with other types of stochastic compartment models still not persuasive. If the intention of the model is to compare the relative effectiveness between interventions and the authors predict that the conclusions are not highly sensitive to parameter changes, how would adding more heterogeneities into the model would result in significant differences in output. Also, if a sophisicated analysis is out of reach due to the long runtime of the model, adding more heterogeneties means adding more uncertainty into the model without being able to manage such uncertainty. This soulds like a disadvangtage of ABM.

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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 #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.

Estimating the impact of interventions against COVID-19: from lockdown to vaccination

PONE-D-21-09294R2

Dear Dr. Thompson,

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,

Martin Chtolongo Simuunza, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #1: All comments have been addressed

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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 #1: Yes

**********

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

Reviewer #1: 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 #1: 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 #1: 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 #1: I am satisfied with the revised version of the papers as the authors have addressed all of my concerns.

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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 #1: No