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PONE-D-20-19492

The Effectiveness of Public Health Interventions Against COVID-19: Lessons from Singapore Experience.

PLOS ONE

Dear Dr. Ansah,

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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: Yes

Reviewer #2: Partly

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

Reviewer #1: Yes

Reviewer #2: I Don't Know

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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 authors study the effectiveness of different interventions in the context of COVID-19 spread in Singapore. They distinguish between containment and mitigation, and use a modified SIR model to show the difference in total infections, peak load and number of deaths. One of the main contributions of the study is also an estimate of total COVID-19 infections (diagnosed and undiagnosed).

In addition to modeling contributions, the article also summarizes the early COVID-19 response in Singapore (e.g., Figure 1), and is a useful historical record. Though dated, the work in this paper is quite useful in highlighting the importance of timely and appropriate response to the pandemic.

Clarifications/Suggestions:

- One of the modifications to SIR model involves differentiating between the detected and undetected individuals. They also account for different infection stages. In terms of description, stating that 'symptomatic infected individuals were disaggregated into two infection stages' seems ambiguous. I think it is cleaner to state that the latent stage is shared by asymptomatic and symptomatic branches.

- Since a lot of the article hinges on the distinction between containment and mitigation, it would be good to add citations to align with the literature. For instance (https://jamanetwork.com/journals/jama/fullarticle/2764956) and (https://jamanetwork.com/journals/jama/fullarticle/2763187) are useful to mention.

- The authors report projected cases by end of current epidemic cycle, however no specific date is mentioned. Likewise, the peak timings are reported in terms of simulation days, than calendar time. It would be helpful if they could use actual months/dates.

- perceived and actual case fatality rate -> case fatality rate and infection fatality rate?

- In Background of Abstract, should it be 'we estimate the actual COVID-19 infections', given that confirmed case counts are publicly available.

- pg. 7 line 82 - Should be Figures 2 and 3.

- It would be good to provide an equation for \\beta given it implicitly captures the infectious population (is the proportion of total population?).

- The authors state the models were validated using case data until June 7th 2020. Would be useful to show these curves in Figure 5, along with the simulated curves (these are in S3, but useful in main paper to show the model fit).

- Though there are multiple parameters listed for the undiagnosed to diagnosed transition, none of them capture the detection probability. Is the fraction of detected infections just a function of the transition rates, or are there any assumptions about the testing protocol?

- How are the uncertainty bounds for the results obtained? Are these same as the +/-25% for selected parameters (the bounds in S8 seem to be much higher)? Which parameters were varied this way?

- The authors state that uninhibited spread would have lead to ~80% of the population infected. This is much higher than the compared scenarios, where the highest is around 4.5%. Is this based on R0=2 and remaining parameters unchanged? What about some of the diagnosis and isolation parameters?

Reviewer #2: 

General comment

The paper "The Effectiveness of Public Health Interventions Against COVID-19: Lessons from Singapore Experience" aims at carring out a counterfactual analysis on the spread of COVID-19 infections in Singapore under different scenarios.

The paper is interesting, well organised and well written for the most part, however several methodological details should be produced and clarified in order to make the anayisis transparent and reproducible, and ultimately, make the reader able to judge on its validity. To this end, data and source code that generated estimates and simulations should be shared with reviewers at least. In the rest of this document, I enumerate the main issues that should be tackled. In the last section, some typos are reported, however a general revision of the manuscript is needed.

In conclusion, I think that the paper is worth of publication in PLOS ONE once the following major questions and issues are addressed.

Major issues

1. [sect. "Methods"] It should be clearly stated what amendments authors made to the SIR or the SIDARTHE model, they should be clearly motivated, and their implications discussed.

2. [pp. 8-9] All equations should be carefully revised. Unlike reference models such as SIR or SIDARTHE, and unlike what stated in the paper (line 111), none of equations (1)-(14) is a differential equation. Moreover, I suggest authors to revise the mathematical notation by including only latin and greek characters: this would improve the readability of the paper. In any case, superscript-like characters such as the superscript turned m and the superscript delta (which are phonetic symbols) should be definitely avoided, as they may be confused with exponents.

3. The meaning and the role of parameters yat (Ѣ) and phi (Φ) in the model is not clear to me. For example, why only a portion yat of diagnosed people is quarantined? Moreover, parameter phi is meant to be "onset to isolation delay" throughout all the paper (except on page 9 where it is defined, and the definitions of phi and yet are switched), however it is not clear to me what term "onset" refers to, expecially if I examine the diagram in Figure 3.

4. [p. 11] It should be clearly explained how "endogenous" parameters are determined, and how calibration is performed.

5. [sect. "Simulated Interventions"] Differences and shared aspects of the scenarios should emerge more clearly, so as to make them more comparable. If choices on the parameters and conditions which distinguish each scenario are justified (when possible), this would definitely improve the validity of the analysis.

6. Authors state that they performed sensitivity analysis, however no comments to the results are provided neither in the manuscript not in the supplementary material.

7. It is not clear how confidence intervals in section "Results" are computed, as the model authors describe is deterministic.

8. On page 14, authors claim that they “explored the impact of (a) immunity on the scenarios explored, and (b) what would have happened if Singapore allowed the virus to dake it natural course without intevention approach”, however no results are provided either in the manuscript of in the supplementary material. Moreover they do not explain how they modified the model (and set the parameters) in order to relax the immunisation hypothesis.

Minor issues

1. Figures S1 and S2 of the Supplementary Material are missing. All the supplementary file should be revised, as there are several figures which are not completely readable, wherease captions and title graphs do not adequately clarify what information is plotted.

2. Second and third items on page 9 would be more easy-to-read if parameters were reported (also ?) along with definitions.

Some typos and other minor details

1. [p. 3, sect. "Why this study was done?", point 1, 3rd line] A quotation mark is missing for keyword "2019 nCoV".

2. [p. 3, sect. "Why this study was done?", point 3] Last sentence says "The list of 30 papers included are provided in the appendix". If authors refer to Appendix S10 of the supplementary material, they could explicitly cite the reference label "S10". Moreover, Appendix S10 actually consists of 31 instead of 30 references.

3. [line 8] Please, specify the date adverb "currently" refers to.

4. [line 82] I think that figures authors refer to are those with numbers 2 and 3.

5. [page 8] Equation number (11) has not been used.

6. [equation 13] Right parenthesis is missing.

7. [line 146] Remove comma after "alpha".

8. [line 154] "denotes" should be "denote", and a space is missing before "kappa".

9. [line 163] "deMotes" should be "denote".

10. [line 213] "will diagnosed" should be "will be diagnosed".

11. [line 220] "...these parameters influence..." should be "...these parameters influences...".

12. [line 260] "it natural course" should be "its natural course".

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Reviewer #1: No

Reviewer #2: No

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The Effectiveness of Public Health Interventions Against COVID-19: Lessons from the Singapore Experience.

PONE-D-20-19492R1

Dear Dr. Ansah,

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,

Kannan Navaneetham, 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 #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 #2: Yes

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

Reviewer #2: Yes

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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 #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 #2: Yes

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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 #2: I am satisfied with the authors' answers and revision of the manuscript, which may be accepted for publication.

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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 #2: No