PONE-D-20-34437

Effect of timing of implementation of containment measures on Covid-19 epidemic. The case of Italy.

PLOS ONE

Dear Dr. Timelli,

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Academic Editor

PLOS ONE

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2. In your Methods section, please give the sources for the following information:

i)    COVID-19 cases

ii)    ICU bed occupancy

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Reviewers' comments:

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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: The authors present a study that shows the impact of the timing of implementation of non-pharmaceutical containment measures (NPMs) on Covid-19 epidemic. They focus on the italian national lockdown, which started on March 11th 2020 and ended on May 4th 2020. The impact of NPMs on healthcare system has been evaluated in 21 italian local administrations (19 regions+2 autonomous provinces). Three indices have been used in order to assess this impact: cumulative incidence (CI), intensive care units occupancy (percentage on the total amount of ICUs), mortality rate. Timing of implementation of NPMs has been calculated as the number of days between the date on which each region reached a CI equal to 1.0 per 100k inhabitants, and the date of National Lockdown (it has been called delay). In the following lines some comments about the manuscript are reported:

1) The impact of the delay on healthcare system in terms of ICU occupancy and mortality rates is not sufficiently assessed. Two scatterplots (as Fig. 3) should be added: one between delay and highest ICU occupancy, the other one between delay and mortality rates (at May 11th). Related correlations should also be reported.

2) Looking at the data on Table 2, correlation between delay and mortality rate is about 0.7, which is close to the correlation between delay and CI. On the other hand, correlation between delay and highest percentage of ICU occupancy is lower (0.38). This probably means that the percentage of ICU occupancy is not the right statistic, and it should be replaced by the number of ICU beds occupied per 100k inhabitants, if these data are available. Percentage in fact is heavily affected by the total amount ICU beds, which is more closely linked to the quality level of the healthcare system than the spread of the epidemic.

3) NPMs effectiveness can be seen after 10 – 31 days (Fig. 1, 2 and 4), regardless of the delay in their implementation. The authors should put a little bit more emphasis on this result, in the abstract and in the Results section.

4) Figure 2 has a very low pixel resolution, it is almost unreadable. Moreover, daily cases have too many fluctuations: it would be better to replace them with weekly averages or moving averages.

5) References are ok.

Reviewer #2: This interesting paper explores how the timing of implementation of NPMs (or NPIs) impacted the cumulative incidence, ICU bed occupancy and mortality related to COVID-19 in Italy. I found the work clear and sufficiently explicative, providing support to modelling studies that suggested that the timing of implementation of control measures is critical to achieving effective control of the epidemic.

Among the strengths, I would mention the clarity of the aims and among the limitations, I would certainly agree that the quality of the data, aggregated, did not allow for in-depth analysis such as age and sex standardization.

The manuscript is very linear and coherent. Moreover, it is technically sound, and the data support the conclusions. Moreover, general conclusions are acceptable and in line with recent literature reports. I particularly appreciated the mention of the data coming from the Italian sero-survey and the report on excess mortality in the limitations section, as it gives a realistic picture of the reality of the pandemic in Italy while acknowledging the struggle of gathering complete data on new cases and deaths.

I believe the statistical analysis has been performed appropriately and rigorously. However, I would add a few details in the Methods/statistical analysis section, both technical, such as the retrospective nature of the study, and on aspects such as the specific software used to perform the analysis,

In Table 1 I would better explain the case-based measures, which do not seem clear.

The authors made all data underlying the findings in their manuscript fully available.

The manuscript is presented in an intelligible fashion and written in standard English, however, I would proofread it as a few sentences might be less clear if some typos are not corrected (e.g. figure 3 “shows a scatterplot by Region of the relationship of CI two months later the date of lockdown”, I believe it should be 2 months “after”), as well as some past tense forms or the s for the third person form of some verbs.

The aims, the discussion and the conclusions are coherent and sound, and ultimately support the adoption of early containment measures in order to counteract the epidemic surge and control its magnitude.

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Reviewer #1: No

Reviewer #2: No

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Effect of timing of implementation of containment measures on Covid-19 epidemic. The case of the first wave in Italy.

PONE-D-20-34437R1

Dear Dr. Timelli,

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,

Simone Lolli

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I am happy to inform you that now the paper is ready for publication. The previously raised issues were addressed by the authors.

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: (No Response)

Reviewer #2: (No Response)

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

Reviewer #1: (No Response)

Reviewer #2: (No Response)

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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 #1: (No Response)

Reviewer #2: (No Response)

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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: (No Response)

Reviewer #2: (No Response)

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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 #1: (No Response)

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