PONE-D-23-37811Analyzing the worldwide progression of COVID-19 cases and deaths using nonlinear mixed-effects modelPLOS 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: Yes

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: I have read this paper. The authors have analyzed the progression of COVID-19 cases and deaths until January 2022 in 156 countries using a nonlinear mixed-effect model based on the SIR framework. Given the major changes in mortality from infection, risk of re-infection and social responses, the analysis was limited to the period before the emergence of the Omicron variant. The impact of infection prevention measures in

various countries was assessed, with a specific focus on estimating the effectiveness of lockdowns, where the effect was assumed to change over time. By accounting for excess mortality, our analysis allowed the estimation of unreported cases and deaths, and thus providing a more comprehensive understanding of the impact of pandemic. In the analysis, we identified gross domestic product (GDP), proportion of people aged 65 years or older, latitude of the capital city on transmissibility of infection, and city population and cardiovascular death rate on mortality rate as significant influencing factors. Furthermore, the differences in transmissibility and mortality rates by variants and the effect of vaccination on the mortality rate were assessed. The transmissibility has increased by odds ratios of 1.2 to 1.4 in Beta, Gamma, and Delta variants; mortality rate has increased by odds ratios of 1.7, 2.2, and 1.4 in Beta, Gamma, and Delta variants, respectively; and vaccination decreased the mortality rate by odds ratios of 0.4 and 0.1 in Delta and other variants, respectively.

The idea of the manuscript is interesting and it can be considered further for a place of publication in Plos One. However, I haver the following queries for the authors:

1. Can authors provide more details on the specific nonlinear mixed-effect model based on the SIR framework that you employed?

2. What led to the decision to limit the analysis to the period before the emergence of the Omicron variant, and how might this choice influence the generalizability of your findings?

3. Elaborate on how the assumption of changing effectiveness of lockdowns over time was incorporated into the model and its implications on the study outcomes.

4. Could you explain in more detail how excess mortality was accounted for in your analysis and how it contributed to estimating unreported cases and deaths?

5. How were social responses, such as public compliance with preventive measures, integrated into the model, and how might these factors impact the validity of your results?

6. Provide further insights into how GDP, proportion of people aged 65 or older, latitude, city population, and cardiovascular death rate were identified as significant influencing factors on mortality rates.

7. Can you elaborate on how the odds ratios for transmissibility and mortality rates were derived for Beta, Gamma, and Delta variants, and how these results align with existing literature?

8. Clarify the methodology used to assess the impact of vaccination on mortality rates, and discuss any potential confounding variables that might influence these results.

9. Provide additional context on the relatively high odds ratio for mortality in the Delta variant compared to other variants, and discuss the potential implications for public health strategies.

10. Detail the sources of data used in your analysis, including information on the reliability and representativeness of the datasets for the countries considered.

11. Can you conduct sensitivity analyses or validation studies to assess the robustness of your statistical methods, especially considering the complexity of the model?

12. Explicitly discuss the assumptions made in the model and their potential impact on the results, addressing any limitations or uncertainties associated with these assumptions.

13. Explore the temporal and regional variability in the effectiveness of infection prevention measures and discuss how these variations might influence your overall findings.

14. Address potential biases in your study, such as reporting biases or selection biases, and discuss their implications for the interpretation of your results.

15. In the conclusion, provide a more detailed discussion on the practical implications of your findings for policymakers and public health practitioners, including recommendations for future interventions.

16. Check the suggested papers: https://doi.org/10.1016/j.chaos.2020.110032; https://doi.org/10.1002/oca.2748.

Reviewer #2: The findings of the research have the potential to get published. However, the manuscript in its current form needs minor revision. Following suggestions should be incorporated while preparing the revised version of the manuscript.

1. It is suggested to write a paragraph on death due to oxygen shortage in hospitals, in the introduction.

2. Is there any source that provides the data of another health issue post-COVID-19?

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Reviewer #1: Yes: Andrew Omame

Reviewer #2: No

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Analyzing the worldwide progression of COVID-19 cases and deaths using nonlinear mixed-effects model

PONE-D-23-37811R1

Dear Dr. Hiroki Koshimichi,

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,

Mohammad Nayeem Hasan

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Comments from PLOS Editorial Office: We note that one or more reviewers has recommended that you cite specific previously published works in an earlier round of revision. As always, we recommend that you please review and evaluate the requested works to determine whether they are relevant and should be cited. It is not a requirement to cite these works and you may remove them before the manuscript proceeds to publication. We appreciate your attention to this request.

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

Reviewer #2: 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

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: Yes

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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

Reviewer #2: 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: All my queries have been addressed and the paper can now be accepted for publication in this journal.

Reviewer #2: (No Response)

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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

Reviewer #2: No

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