PONE-D-21-01356

Multilevel modeling of county-level excessive alcohol use, rurality, and COVID-19 case fatality rates in the US

PLOS ONE

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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: No

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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: Summary:

This study wanted to determine if county COVID-19 case fatality rate could be predicted by the 9-level grouping of alcohol use (low, medium, high) and rurality (low, medium, high) levels, while controlling for state, and other health factors (such as smoking, age, diabetes, etc.). They found that, contrary to their exploratory hypothesis, there were lower case fatality rates in higher alcohol-using and more rural counties than the baseline (low alcohol, low rural).

This manuscript is well-written and covers a relevant topic. Furthermore, the model design is well-founded and had appropriate controls and justification. Finally, the results were very interesting, as they were the opposite of what is expected and had a nice bevy of detail. The major weakness of the manuscript was an incorrect assertion in the discussion/conclusion about the burden of COVID-19 which was not supported by any results. A related weakness is the call-to-action statement, which was in no way justified by the results.

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Specific Areas of Improvement:

Abstract:

Major:

Page 2, Line 23-27: Your conclusion has a call-to-action that includes alcohol prevention/treatment in the pandemic response plan. While mitigating alcohol abuse is a good in of itself, increasing efforts based on the pandemic is not supported by your results. Counties with higher alcohol levels had lower case fatality rates. You shouldn’t include such a call-to-action unless you can convincingly demonstrate why, despite the contrary results, that such a response is warranted, and I don’t see how you could.

Minor:

Page 2, Lines 15-17: consider adding ‘while controlling for confounding factors’ to the model description.

Page 2, Line 21: p-values should have consistent significant digits (I typically see 3-4 as the preferred number in other manuscripts).

Introduction:

Major:

none

Minor:

none

Methods:

Major:

none

Minor:

Page 5, Line 5: For the COVID-19 deaths, you used only the most recent 3 months. Is there a reason why? That time period, while likely a reasonable approach, should be justified.

Results:

Major:

none

Minor:

Page 12, Lines 2-4, 5: As noted in the abstract, the p-values should have consistent significant digits.

Figures and Tables:

Major:

none

Minor:

Table 2: The header for the binge drinking column is much longer than the other headers. Perhaps shorten the header for binge drinking and give the additional information into the table description [example for revised header: Excess drinking (%)].

Table 3: For the second column header, change the B to β to match the format from the text portion of the results. For the p-value column, again set the p-values to consistent significant digits.

Discussion:

Major:

Page 14, Lines 4-7: You write that the burden of higher case fatality rates lay predominately in mid alcohol use/mid rural and high alcohol use/high rural counties. This is not what the results show. High alcohol use/high rural counties had the lowest case fatality rates, while mid alcohol use/mid rural had lower rates (though not significant) to the referent (low alcohol/low rural). These two sentences need to be revised to reflect what the results found.

Page 14, Lines 19-23; Page 15, Lines 1-7: You write that alcohol consumption during self-isolation poses a substantial public health challenge. However, none of your results provide any evidence for this claim. The three categories of counties with high alcohol had the lowest case fatality rates (1.48%, 1.25%, and 1.20%, from Table 1). Furthermore, even looking at the top 10 highest and lowest alcohol abuse counties, the average case fatality rates are far lower in in the highest (0.646%) compared to the lowest (2.308%) (values calculated by averaging the case-fatality-rate values in Table 2). As noted in the abstract, while mitigating alcohol abuse is a good in of itself, increasing efforts based on the pandemic is not supported by your results. This whole section needs to be dropped or revised to justify such action despite contrary results (which I do not see how you could).

Page 15, Lines 21-22; Page 16, Line 1: This sentence needs to be corrected in the same way as the Page 14, Lines 4-7.

Page 16, Lines 3-5: This call-to-action sentence, like the section of Page 14, Lines 19-23; Page 15, Lines 1-7, has no support from your results. It should not be included.

Minor:

Page 14, Line 5: the word ‘lied’ should be ‘lay’

Page 15, Line 8: The biggest potential limitation is that this is an ecological study (i.e., the data was aggregated at the county level, so individual metrics were not available). You cannot know if the population that made up the cases and deaths have the same demographics as the other variables (rurality, alcohol use, etc.). While this may well be an obvious statement, it is good to mention it since you’ve included a section on potential limitations.

Page 15, Line 20: For your conclusion, because of the following the facts: 1) the results were contrary to expectations, 2) it was an ecological study, and 3) you’re trying to give alcohol prevention recommendations, it may be a good idea to outline a future experiment that would test the link between mortality and alcohol use on an individual level.

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Specific Areas of Achievement:

Abstract:

Objective, methods, and results sections were clear and concise, presenting the reader with an understandable summary of your project.

Introduction:

Page 4, Lines 20-23: The statement of the project and the hypothesis are good additions.

Methods:

Page 7, Lines 10-23; Page 8, Lines 1-3: the description of the model building and selection was very clear and well justified. I thoroughly enjoyed reading this section.

Results:

Short and to the point. It conveyed the major results while letting the details reside in the appropriate figures and graphs.

Figures and Tables:

Figure 1 was particularly well made. Tables were clear and informative.

Discussion:

While the call-to-action was no appropriate for the results found, I do like the attempt to translate results into action.

Reviewer #2: This paper explored the relationship between county-level excessive alcohol consumption, rurality and COVID-19 case-fatality rate using multilevel beta regression analyses. The authors make a compelling argument for the pathway through which a higher prevalence of excessive alcohol consumption may affect COVID-19 fatality. They also make a compelling argument in the discussion section about potential reasons for the reversed associations between the outcome and focal predictor. The paper is methodologically sound. However, as indicated in the feedback below, some of the discussion and conclusion points are in contrast to the results shown in the tables. Minor revisions are suggested.

Tables.

Table 1. For ease of readability, the authors should consider providing summary statistics in table 1 for only the covariates (second part of table 1) and having the first part showing case-fatality rates for values of the focal predictor as a separate table.

Table 3. The low alcohol mid rurality coefficient is reported as 0.00, the coefficient should be rounded to a non-zero value. Same applies to “percentage of a county’s adult population with a BMI of 30 or higher” covariate and several standard errors.

Discussion.

Page 14 line 4-6 “We found that the burden of higher case fatality rates lied predominately in mid alcohol use/mid rural and high alcohol use/high rural counties.” However, table 3 shows that the mid alcohol /mid rural was not statistically significant and also did not have the largest effect size (the mid alcohol/high rural and high alcohol/mid rural were significant).

Page 15 line 2 “Given indications that alcohol use is associated with higher COVID-19 mortality in some areas,…” this is in contrast to the index study finding and the authors do not provide any citation to support the statement.

Page 15 line 21-page 16 line 1 “our findings demonstrate disparate COVID-19 fatality burdens in some counties, in particular counties with mid/high excessive alcohol use and counties with mid/high levels of rurality.” This again is not supported by the study findings. Table 1 and table 2 indicate that the case fatality burden is more for the low alcohol/low rural counties.

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Reviewer #1: Yes: Mark R Williamson

Reviewer #2: No

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Attachments

Attachment

Submitted filename: Comments_PLOSone_03.24.2021.pdf

Multilevel modeling of county-level excessive alcohol use, rurality, and COVID-19 case fatality rates in the US

PONE-D-21-01356R1

Dear Dr. Pro,

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,

Antonio Palazón-Bru, 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 #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: (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: Yes

Reviewer #2: (No Response)

**********

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: Revised version looks good. A strength of this manuscript is the clarity of statistical analysis and the use of a single variable to capture both alcohol usage and rurality into categories.

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: Yes: Mark R Williamson

Reviewer #2: No