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PONE-D-22-05387Characterizing changes in behaviors associated with chemical exposures during the COVID-19 pandemicPLOS ONE

Dear Dr. Herbstman,

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" Research reported in this publication was supported by the Environmental influences on Child Health Outcomes (ECHO) program, Office of The Director,

National Institutes of Health, under Award Numbers U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319 (PRO Core), and UH3OD023290 (Columbia University, New York, New York: Perera FP, Herbstman JB); UH3OD023275 (Dartmouth College, Hanover, New Hampshire: Karagas MR); UH3OD023272 (University of Illinois, Urbana: Schantz SL, University of California, San Francisco: Woodruff T, University of California, Berkeley, Morello-Frosch, R); UH3OD023271 (University of Washington, Seattle: Karr C, Sathyanarayana S); and UH3OD023313 (Memorial Hospital of Rhode Island,Pawtucket: Deoni S, D’Sa VA; Brown University, Providence,RI: Braun J)"

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" Research reported in this publication was supported by the Environmental influences on Child Health Outcomes (ECHO) program, Office of The Director, National Institutes of Health, under Award Numbers U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319 (PRO Core), and UH3OD023290 (Columbia University, New York, New York: Perera FP, Herbstman JB); UH3OD023275 (Dartmouth College, Hanover, New Hampshire: Karagas MR); UH3OD023272 (University of Illinois, Urbana: Schantz SL, University of California, San Francisco: Woodruff T, University of California, Berkeley, Morello-Frosch, R); UH3OD023271 (University of Washington, Seattle: Karr C, Sathyanarayana S); and UH3OD023313 (Memorial Hospital of Rhode Island, Pawtucket: Deoni S, D’Sa VA; Brown University, Providence,RI: Braun J)."

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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

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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

Reviewer #3: 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: This cross-sectional survey of behavior-change related to environmental exposure among 1535 members of the ECHO-wide Cohort identified patterns of behavior change among cohort members during the COVID-19 pandemic that could have altered their environmental exposures, particularly through altered diet and the use of cleaners and personal grooming products. This study examines a novel research question related to the COVID-19 pandemic. It is exhaustive in terms of assessing a wide range of potential behavior changes and testing all potential predictors of behavior. It is too bad that it does not yet have information on how much behaviors changed (A lot? A little? Enough to make a difference to health-relevant exposures?) or, as the author’s point out, any direct assessment of chemical exposures. But there are plans to gather such information. In its current form this manuscript provides preliminary evidence of a potentially important trend in environmental exposures among the US population over the past 2 years, one which could motivate further studies / be of use to researchers interested in environmental exposures who might hope to leverage the natural experiment of the pandemic. I note a number of issues that, if addressed, could improve the manuscript.

Major comment

A key limitation of this study is that its wider utility likely hinges on its potential to generalize to the larger US. However 67% of respondents were from New Hampshire and the respondents were largely white, well-educated, and free of covid infection. What I believe is currently missing is a breakdown of what percent of respondents were from each of the 9 cohorts / states (this could be added to Table 1) and some discussion of to what extent we can generalize these findings beyond this particular sample of participants. The potential for wide geographic coverage in this study could be a significant strength - but is this sample generally representative of any populations?

Relatedly, I struggled at times as a reader to identify the clear utility of this study in its current form for the wider field (and not just the ECHO-wide Cohort researchers who plan to follow-up with a panel of urinary biomarkers). Why not just wait for the biomarkers to create a more complete research product? I suspect that the goal is to provide evidence of a potential national trend in behavior change so that other researchers need not wait for the next level of evidence before investigating further. But this was not stated explicitly. I say this because I think that the authors could spend more time throughout the manuscript better enumerating the motivations behind the study and the ultimate implications (in the abstract and introduction in particular). The idea that “prevention strategies and campaigns that limit environmental exposures, support stress reduction, and facilitate behavioral change may lead to the largest health benefits in the context of a pandemic” struck me as speculative and overly broad / non-specific to this particular manuscript’s findings, which are that participants reported changing their behavior during the pandemic, with participants reporting more stress also more likely to report behavior change. To me the big selling point is that this study identifies the exposures for which the pandemic may likely be a useful natural experiment - but perhaps there are other implications I am missing as well.

Minor comments

Minor comments are provided on lines or sections below. A number of typos throughout hindered readability.

Abstract

- Rationale for the study was not clearly articulated before the methods were described. (e.g., Objectives).

- Line 21 - ECHO-wide Cohort is mentioned but not described. A few brief words here would aid the reader unfamiliar with ECHO and provide necessary context for the study.

- Line 30 - “increased COVID-related stress” suggests longitudinal change over time. Suggest replacing with “greater COVID-related stress” unless the comparison was dichotomous (stress vs. no stress), in which case the language should reflect that instead.

- Line 32 - suggest stating “less chemical exposure”

Line 83 - I believe the causal evidence is overstated. Suggest changing text to “psychosocial stress may interact…”

Line 92. Please describe the ECHO-wide Cohort.

Line 94 - typo “?”

Line 127 - the manual acronym is DSM-5, not DSM-V. Suggest spelling out in the first instance.

Line 129 - Further context on the DSM-5 definition of traumatic events may be useful here, as the definition is narrow and it is possible that many of the respondents may not have been truly exposed to a traumatic event (particularly given the low COVID-infection rates reported). The DSM-5 definition of a traumatic event requires “actual or threatened death, serious injury, or sexual violence.”

Line 172 - what is NOVA?

Line 401 - typo “that reduce”

Table 2

- I think it is confusing to place “processed food” in both the “less than” and “more than” columns. I suggest picking the question that is of most interest and dropping the other use. Same comment for Figure 1.

- Table 2 also makes clear the large number of tests conducted. I appreciate that these predictors of behavior change tests are not the primary study tests, however the readers may be more confident in the findings if the authors note which associations remain significant after some form of correction for multiple testing (e.g., FDR).

Figure 1 - Figure 1’s title may mislead the casual reader into concluding that the y-axis describes how much a particular behavior has increased or declined on average for respondents when, as I understand it, the figure instead displays the the percent of respondents who reported doing less or more of something. I suggest amending the title or adding a footnote that makes it clear the “percent” on the y-axis is the “percent of respondents reporting less frequent or more frequent behavior”.

Figure 2 makes a clear and compelling case for behavior change increasing alongside stress symptoms. Well done. I suggest moving the effect estimates on the right side so that they overlap less with the confidence intervals for the 3+ More Processed Food category.

Authors note that they “cannot discern from our study whether stress leads to behavior change, whether

behavior change leads to stress or whether they occurred concurrently.” The authors may also wish to consider that having the same individual rate their stress and their behavior change may result in inflated estimates of an association owing to single-method, single-reporter bias (e.g., owing to participant reporting style, personality, etc.). Having third party or objective measures of one of these variables may give better estimates of the true association.

Reviewer #2: This is an interesting analysis on an important topic; and there is a lot of interesting data that were collected and analyzed. At the same time, there is concern regarding the way the study and results are presented: the manuscript is highly focused on the fact that the behavior changes during the pandemic likely relate to changes in environmental exposure and health risk - most of the text in the abstract, introduction, and discussion are focused on this point. However, no data were collected directly about environmental exposures, which means that the major talking points of the manuscript are speculative, rather than based on data presented. The data collected include whether behaviors increased/decreased and stress. This is still important and interesting; foccusing more on the data/results that were observed in this specific study is recommended. Additional comments are below.

*Abstract: Overall, the abstract seems to be fairly general. The amount of background could be shortened. The main finding here is that increased stress is correlated with more behavior change; but the majority of the abstract focuses on something that wasn’t measured – the impact of this on environmental exposures. In this light the conclusions of the abstract do not seem to directly derive from the results of this study.

*Abstract. Key specific, numeric, results should be included.

*Line 29: What is meant by “common predictors”?

* Line 121: The authors state that data collection is ongoing; what is the rationale for publishing the results now before the remainder of the data are collected?

*Methods/CEE Survey: Was this survey pilot tested or otherwise assessed for quality?

*Methods/Acute Stress Survey: It appears that the authors have already published about development of the acute stress survey; however, it would be good to explicitly state whether these adaptations were validated in the text here as well.

*Line 153-4: It’s very reasonable to think behaviors changed as the pandemic progressed; but what was the reason to make a comparison based on just early vs. late and was there a reason for selection of March 1, 2021 as the cutoff date?

*Line158-9: “Our analyses focused on outcomes that varied” It’s not clear what is intended by this statement. Also, in this section it seems that you only selected outcomes where none of the participants responded that they had no change. Although I see the explanation further down in the paragraph, this section is confusing and could be clarified.

* Line 197: the percent missing for marital status is fairly high; would this affect the accuracy of the imputation?

* Results: How do the demographics of those who are included in this analysis correspond to the overall ECHO cohort?

* Line 367: I wouldn’t refer to the fact that you are “speculating” about changes in environmental exposure as a strength of the study.

* Line 389: I don’t understand why a survey response rate couldn’t be calculated based on the number of people offered the survey and the number who completed it.

* Line 392: what is meant by a “virtual” cohort study? Also, can this really be called national when the responses are dominated by rural women from NH?

Reviewer #3: Line 39-42: Recent research indicates that air pollution has returned to pre-pandemic levels as recently as February 2021 – please adjust to reflect these data or change the wording to reflect that they have rebounded.

Line 121-125: The study is primarily coming from New Hampshire, which is a very racially homogenous (93% are white alone) state and low in overall population, comparatively speaking. This is an impressive study – as such, what is your rationale for reporting premature results from mostly NH alone, given the substantial generalizability issues and potential for bias? I worry that in trying to tease out racial effects, you’re instead looking at a very small group that could be experiencing heightened stress already because of being an extreme minority, as one example.

Line 147-155: Are you saying here that you are comparing impacts from early COVID outbreaks to later stage COVID (e.g., post vaccine)? If so, it may benefit you to explicitly mention this, as there are many disparate factors that can impact these results.

Line 181-185: It seems like stress and eating behaviors are a bidirectional relationship. Do you have some method to help control for this?

Line 211-214: This is a small percentage of participants who are pregnant. My impression was that this was an area of interest, as pre and perinatal outcomes are highlighted as very important in the introduction.

Line 209-223: I am reminded of the many other stressors that were extremely likely co-occur during this same time in these states; namely, there has been a good deal of research identifying that political stress is matched alongside pandemic stress, with pandemic stress decreasing slightly over time while political stress remained static. There are major differences here by race, ethnicity, and occupation. Do you have any way of controlling for other stressors? Do the COVID questions specifically inquire about stress related to the outbreak of COVID?

Line 255-265: Are these significant? If so, please specify.

Line 267-278: Please specify which relationships are not significant.

Line 276-278: Fascinating.

Line 283-287: These factors seem like they would be highly correlated. Is there a risk of collinearity here?

Line 280-293: I am confused by the decision to use percentages and p values separately and struggle to track what relationships are significant and to what magnitude, both in size of difference and significance. This undermines the strength of the paper.

Line 330-335: I am confused by this paragraph. Please try and clarify the message.

Line 337-344: Could this not be because of the sample sizes? I don’t think it’s fair to assume that these results can be used to anticipate subpopulations who are more likely to be exposed to a variety of chemicals, especially in the context of the complaints I have raised above.

Line 346-354: This is a great paragraph.

Line 362-368: While I do agree with most of this, this is not a diverse population in terms of geography, race, or ethnicity. This statement should be removed.

Line 370-389: I appreciate the candor by which the authors reflect on the limitations of the study. However, I feel it is a major flaw that you cannot truly account for COVID-19 related stress alone. My understanding of the paper is that you are assessing for stress during COVID-19, but not directly measuring stress as a result of COVID-19 alone. Is this a fair assessment? If so, I think this should be discussed in this section.

Line 391-403: I think the authors next step should be to analyze this same relationship in a complete population, rather than the limited scope identified in this paper.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Characterizing changes in behaviors associated with chemical exposures during the COVID-19 pandemic

PONE-D-22-05387R1

Dear Dr. Herbstman,

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,

Aaron Specht

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 #3: 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 #3: Partly

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

Reviewer #1: Yes

Reviewer #3: 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 #3: 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 #3: 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 satisfied with the authors' responses and manuscript changes in response to my comments on the first round of peer review. I commend the authors on a thorough revision and a manuscript that will be of interest to many readers.

Reviewer #3: Thank you for addressing the comments! This is a great paper. I do disagree with some statements; notably, the somewhat misleading decision to describe the population as diverse given its clear homogeneity. I also feel that the authors should wait until they have completed data collection before publishing. However, in its current form this draft is suitable for publication and I support it moving forward. Excellent work!

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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: Aaron Reuben

Reviewer #3: Yes: Christian Hoover

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