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PONE-D-20-29820

Modeling the evolution of COVID-19

PLOS ONE

Dear Dr. Koutsou,

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 carefully follow the recommendations of both reviewers. The criticism of reviewer #1 is very strong, but you should try to overcome it by a detailed discussion in the text of the paper on all raised questions.

Please submit your revised manuscript by Mar 13 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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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.

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We look forward to receiving your revised manuscript.

Kind regards,

Vygintas Gontis, Ph.D.

Academic Editor

PLOS ONE

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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: No

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: Yes

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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: Please see file in attachment.

Reviewer #2: In the paper under review, the authors give a detailed study of two models: first is the

modification of classical deterministic SIR model for epidemics in the case when the transition rates between the corresponding compartments are incorporated. Second model is a particle model, in which the disease is transmitted through particle collisions and infection rates are varied by adjusting the particle velocities. Both models are applied to Cyprus data.

It is needless to say that there are thousands of papers and approaches for COVID modelling and, clearly, it is almost impossible to choose which is the right one. The authors decided to choose the simple models with a minimal number of parameters, what is rather well motivated in the case of small countries such as Cyprus. However, in general, the long-term COVID forecasting based on a mathematical model (especially deterministic SIR-type) is very questionable (see [1], [2]), especially

when making the assumptions of the model.

In the context of many COVID modelling approaches, the subject and results of the paper are interesting enough, the paper is well written and I recommend it for publishing in the journal. Below, please find

a list of comments.

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Reviewer #1: No

Reviewer #2: No

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Attachments

Attachment

Submitted filename: report_PONE-D-20-29820.pdf

Attachment

Submitted filename: ahiks.pdf

PONE-D-20-29820R1

Modeling the evolution of COVID-19 via compartmental and particle-based approaches: application to the Cyprus case

PLOS ONE

Dear Dr. Koutsou,

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.

Your revised version of the manuscript is almost acceptable for publication. Nevertheless, you should carefully take into account the recommendations of the reviewer after the second reading of your manuscript. 

Please submit your revised manuscript by May 15 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,

Vygintas Gontis, Ph.D.

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: Partly

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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 would like to thank the authors for their resubmission.

The authors have partially addressed my main concerns.

However, their replies and, more importantly, the changes they have made to the manuscript are not yet enough to grant publication. I will detail below what remains to be clarified. If the authors manage to convincingly address the following points I would be happy to recommend publication of their manuscript.

MAIN COMMENTS

(1)

Limitations to the forecasting potential of the model.

In my previous report this was the main criticism to the manuscript. The authors have partially addressed it but mostly in their reply. They must state the limitations more clearly and make them more evident in the manuscript.

For instance, concerning the statement:

“This study also demonstrates the success of these models when relatively small numbers of cases are involved and for which statistical models yield results with very large uncertainties.” I find it difficult to claim the modeling was successful. The authors must state that the predictions are reliable only for short period of times and only if the future evolution of infection rates and testing rates is specified in detail.

I still find the long-term predictions shown in the plots to be too far fetched and potentially misleading if employed for policy-making.

In order to give an intuitive measure of how restrictive the limitations of the models are, the authors should show, together with the predictions, the actual development of the confirmed case. This additional information would give a clear representation of how severe the limitations are and make it easier to appreciate that the value of these kinds of models is mostly on short term predictions.

The actual time evolution of the confirmed cases must be shown in all panels of Figure 4, 5 and 6.

If the plots become difficult to read because of the difference in magnitude between predictions and reality the authors can provide additional figures. However, I strongly recommend that in each figure both predictions and confirmed cases are always shown.

(2)

The authors state “We stress that additional scenarios can be analyzed to reflect new different circumstances as they evolve e.g. an increase of cases from incoming people, etc. The strengths of the models is that they can be

adjusted to new measures and human behavior by adjusting the reproduction number. We include an addendum with an example of how these measures can be included using data that have become available after submission of this work.”

I would recommend adding a statement to stress that this is not completely trivial and that it can become difficult to interpret what the new evolutions of the reproduction number mean. For instance, is there a possible interpretation for these 7 step-like changes that are used for fitting the additional data? How would one account for smooth changes in the reproductive number such as the ones usually due to seasonality?

The authors must comment on this in the manuscript

(3)

The authors state “We find our fits are robust to small changes r0 and r1 as long as their ratio is maintained and excluding extrema such as …” It would be good to see a more quantitative assessment of this statement, perhaps plotting what changes in the predictions using different choices of r0 and r1.

(4) The additional plots provided by the authors in reply to my former question (4) and parts of the authors’ reply should be included in the manuscript. This would make it easier to quantify their statements

(5) The reply to my former question (7) contains useful information, it should be added in the main text. Also, more importantly, the plots should not cut the values of scenario A for the compartmental model. The use of insets may help the author provide all the necessary information.

OTHER COMMENTS

(1) The authors introduced a remark that is useful to better appreciate the value of the their two, complementary, modeling approaches. However, the new statement “This leads to confidence on the model forecasts on one hand, but also allows us to attribute different errors to the predictions, since the particle model exhibits stochastic errors, related to how the pandemic was seeded within the population, while the compartmental model exhibits modeling uncertainty, based on the uncertainties of the fitted parameters." requires some clarification.

It seems like the stochastic models require parameter fitting as well. It would be more precise to say that their uncertainty is due both to stochasticity and uncertainty in parameters.

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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.

Modeling the evolution of COVID-19 via compartmental and particle-based approaches: application to the Cyprus case

PONE-D-20-29820R2

Dear Dr. Koutsou,

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.

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Kind regards,

Vygintas Gontis, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: