PONE-D-22-26146The impact of COVID-19 vaccination in the US: averted burden of SARS-COV-2-related cases, hospitalizations and deathsPLOS ONE

Dear Dr. Yamana,

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.

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Comments were kindly provided by two reviewers. I concur with Reviewer 1's suggestion that the authors clarify whether the indirect effects of vaccination were considered in the present study. If not, I would incline that authors can discuss any potential impact on the proposed result. Furthermore, please add a detailed method and validation of the proposed model for naive readers.

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Please submit your revised manuscript by Dec 08 2022 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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"TKY, MG, SP and JS are employees of Columbia University, which received funding from Pfizer in connection with the development of this study and of this manuscript.  JS and Columbia University disclose partial ownership of SK Analytics. JS discloses consulting for BNI. MDF, FJA, MMM, and FK are employees of Pfizer and may hold stock or stock options. DS was employed at Pfizer at the time this work was conducted and he may own stock or stock options."

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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: Partly

Reviewer #2: Partly

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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: 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: Vaccination programs contributed to preventing the number of infected with SARS-CoV-2, hospitalizations and deaths related to COVID-19 worldwide. Quantifying the averted those burdens is crucial to evaluate the impact of the vaccination and decision-making at the time. Using the meta-population model, the authors tried to estimate the numbers of prevented SARS-CoV-2-related cases, hospitalizations and deaths attributable to vaccination in the US. Because the authors applied the model previously published in a few scientific journals, I believe the model could be robust even in the current context of the manuscript. However, I have some comments on the manuscript, so I would like the authors to consider them carefully.

In terms of the characteristics of the effectiveness of the vaccination, could the authors clarify it? The effectiveness would be divided into two: direct and indirect. I presume that the authors estimated the direct effect of vaccination because they did not take into account the reduction of the transmission rate of vaccinated people. I would be grateful if the authors discussed such effectiveness using the cited references (e.g., Israel’s study explored the direct effect but not the indirect one).

Please provide the fitted baseline scenarios for counties or states; otherwise, it is difficult to judge the scientific validation of the calibrated mode.

I would recommend that the authors provide information on the model even though the model was previously well described elsewhere. For example, how did the authors cooperate vaccination into the model? Unfortunately, I could not understand how they were considered even though I read the Supplementary Material. Please share the equation.

I agree with the advantages of the meta-population model that could capture the various characteristics of county or state-specific. However, some measures, e.g., CHR and CFR, are very important to consider the discrepancy between age groups. Therefore, please validate the usage of averages of such measures by showing the comparison between observed values and estimates of the hospitalizations and deaths from baseline scenarios, for example.

I do not understand why the authors calculated averted hospitalization costs. Please provide more insights obtained from the analyses in the discussion.

In the result, the authors showed that 74.1% were susceptible on 14 December 2020. It would be great if the authors compared this value and observed one, possibly from serological surveys, in order to validate the baseline model.

Please provide results shown in Table 1 for each county or state as tables or figures (cumulative) in the result or Supplementary Material.

Although the authors mentioned some results (i.e. averted cases, hospitalizations and deaths) estimated from previously published studies, there are no mentions of the methodology differences. For the direct effect of the vaccination, averted cases and hospitalizations can be calculated by the difference in incidences between unvaccinated and vaccinated. Why did the authors use the meta-population model? If the interactions between counties or states, why do not explore the insights (e.g. difference between states) further? Those points need to be described more in the manuscript.

Reviewer #2: This paper aims at caracterizing the averted covid-19 burden from vaccination in the first 6 months of the campaign in the US. It's a short paper, to the point, with a simple application of an already developed model. While the paper is suitable for publication in PLoS One, I think there are some barriers to have it published as it is.

Mainly, a lot of details are lacking in understanding the paper. Mainly the methods are not described fully (but available from other papers), and some diagnosis figures (posterior predictive checks or equivalent, vaccination baseline scenario model fit ...) are missing.

Some other remarks:

One question: why model at county scale but only present results at national or state-scale ?

« We modeled the vaccine as producing direct effects only » but with susceptible depletion, aren’t some indirect effects also taken into account in this model ?

A lot of simplifying assumptions are made but the discussion does not detail enough their possible impact on concusion (especially focusing only on the first six month without omicron, not using an age-stratified model, no discussion on delayed vs averted death, )

"All 3 scenarios show that vaccination benefits were limited during the early months of vaccine rollout" This might an artifact from the age-prioritization of covid-19 no ?

What makes the model finding so different from other modeling studies cited in the conclusion ?.

The paper is not standalone:

"and its [the model] full details are described in Pei & Shaman [4]."

"Parameter values for μ, Z, D and θ are assigned according to the values inferred in Pei and Shaman [4]."

Figure S1 is refered nowhere in the main text nor in the SI text.

So with the addition that the code is not shared yet, nor are figures of model fits, so it's really hard to provide a proper review of the paper. Especially as this study is sponsored by Pfizer, there should be a strong justification of the conclusions from the methods, which I cannot judge due to the lack of insight.

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Reviewer #1: No

Reviewer #2: No

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PONE-D-22-26146R1The impact of COVID-19 vaccination in the US: averted burden of SARS-COV-2-related cases, hospitalizations and deathsPLOS ONE

Dear Dr. Yamana,

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 submit your revised manuscript by Apr 10 2023 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,

Sung-mok Jung

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.

Additional Editor Comments (if provided):

The manuscript has been well revised overall. However, I concur with Reviewer 1's comment regarding potential biases in CFR and CHR. Such naively calculated CFR and CHR may have been underestimated if the time delay from infection (or confirmation) to death (or hospitalization) was not fully taken into consideration, especially if the epidemic size exponentially increased in the corresponding period. Thus, I would like to strongly recommend that authors reestimate the CFR and CHR while taking the time delay distribution into consideration.

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)

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: Partly

Reviewer #2: Yes

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

Reviewer #1: Yes

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 #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

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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: I am concerned about CHR and CFR. When the authors estimated CFR as dividing cumulative deaths reported between Aug 1 to Dec 14 2020 by cumulative cases infected during the same period, it may lead to an underestimate due to the right censoring issue of reported deaths (reporting delay between infection and death), especially in the case the magnitude of infections is large in the late period.

Reviewer #2: Thanks for including the code and for making the paper standalone. I appreciated the comments added in the description.

I do not have any comment that would require another review. Just two things, not mandatory

- l106: . "We modeled the vaccine as providing 90% effectiveness against infection"

I think "and transmission" should be added there to make sure there isn't any misunderstanding. (perhaps that could be also mentionned in discussion).

- fig S2: any tentatitive explanation of why Rt is higher in winter than in summer would be welcome. I do think this figures should be in the main text (with another pannel being vaccines uptake ?).

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Reviewer #1: No

Reviewer #2: No

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The impact of COVID-19 vaccination in the US: averted burden of SARS-COV-2-related cases, hospitalizations and deaths

PONE-D-22-26146R2

Dear Dr. Yamana,

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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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,

Sung-mok Jung

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I appreciate the authors’ effort in integrating all the comments in the manuscript. The manuscript has been well-revised, and in my opinion, it is now ready for acceptance. However, if the authors could clarify how exactly the reporting delay was considered in the calculation of CFR and CHR (e.g., assuming identical delays across all cases or back-projecting the epidemic curve with the distribution), that would be more helpful for naïve readers to follow. Again, congratulations!

Reviewers' comments: