PWAT-D-23-00083

Using Detrending to Assess SARS-CoV-2 Wastewater Loads as a Leading Indicator of Fluctuations in COVID-19 Cases at Fine Temporal Scales: Correlations Across Twenty Sewersheds in North Carolina

PLOS Water

Dear Dr. Christensen,

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Vikram Kapoor, Ph. D.

Academic Editor

PLOS Water

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Comments to the Author

1. Does this manuscript meet PLOS Water’s publication criteria? Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe methodologically and ethically rigorous research with conclusions that are appropriately drawn 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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Reviewer #1: Yes

Reviewer #2: Yes

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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 article by Hoffman K and Holcomb D, et al., describes a thorough process by which they optimized smoothing models for COVID-19 wastewater surveillance in North Carolina. While there are numerous manuscripts discussing the lead-time for wastewater data compared to clinical data, there aren’t as many comparing the smoothing models used to improve data interpretation. I have some minor suggestions for revisions before the manuscript is ready for publication.

Line-by-line comments

• Lines 57-59: there is also some research that suggests minorities in America had higher per-capita test rates compared to white Americans, but they often had worse disease outcomes than white Americans (see Kaiser Family Foundation report). It was unexpected based on the historical marginalization, think about how behaviors and beliefs about the pandemic might have upended what was expected about the per-capita testing rate by race.

• Table 1: were all sites sampled 2x/week? Suggest adding this information to the table if not or re-stating sample frequency here

• Line 168: say the LOD here

• Line 258-259: move the “Figures 1c and 1d” reference to line 258 after “detrended cases” and cite 1a and 1b at the end of the sentence, was confusing to read which was referring to which in the figures

• Line 262: explain the pairwise correspondence in the context of the R values

• Line 265: are detrended residual data anywhere? In supplementa?

• Line 274: might consider explaining Spearman’s rho a bit to the reader, can’t guarantee all readers are familiar with this

• Line 276: what is the maximum correlation value?

• Figure 1c: should the y-axis title include residual? Took me a while to figure out I wasn’t just looking at the same data from 1a with a different scale, also in general negative residuals are a bit difficult to interpret, might consider explaining this a bit

• Line 311: ML, do you mean mega liter? Clarify this, a common flow metric is MGD = million gallons per day, might be confusing for some US readers

• Lines 311-312: what about daily average flow? Capacity is not the same as what they process on average

• Line 364: which of the five sewersheds are these? Is it in a figure? Table?

• Lines 472-473: can you update these metrics for 2023?

• Line 478: I’m not totally convinced that 8 weeks is considered a fine scale, compared to the whole pandemic period yes but 8 weeks is 15% of the year

• Lines 490-501: clarify that it is unknown if these public health interventions helped, more program evaluation is needed in general for these types of Public Health actions

General comments

• Unsure why italics are used throughout to put emphasis on certain words, suggest removing

• Make sure to cite the supplemental information, I found myself wondering where certain plots were (line 346) only to realize they were in the supplemental.

• Suggest making a table with the descriptive data included in “Wastewater Loads and COVID-19 Incidence Across All Sites” section, would be helpful to see all data by WWTP and then overall w/ some type of description of spread of data (95% CI, IQR, std dev, etc.)

• Digital quality of most of the figures isn’t great after downloading, suggest increasing DPI for publication so they’re less blurry

• I’m interested to see how these lead times compare to non-detrended data, are there improvements? Is it just less noisy and that’s why its better? A more thorough discussion about why this is improved upon just normal trend analysis is warranted, especially since it requires quite a bit of computational work

Reviewer #2: Wastewater-based epidemiology (WBE) is an upcoming filed, which contributed significantly to the understanding of virus transmission during the pandemic. Several studies have used viral titers in wastewater to predict the trajectory of the pandemic. WBE is thus an important tool, which needs to be refined for future applications in public health.

The study is a good example of applied WBE. The authors have used detrending time series and analyzed the lead or lag times in the temporal changes in wastewater viral titers and clinical case numbers. Statistical support was demonstrated in most cases suggesting the reliability of such techniques in predicting the spatiotemporal distribution of viral transmission in cities with wastewater treatment plants. The authors make a strong case for the use of such analyses in refining the methods used to interpret data generated using wastewater.

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Reviewer #1: No

Reviewer #2: No

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Using Detrending to Assess SARS-CoV-2 Wastewater Loads as a Leading Indicator of Fluctuations in COVID-19 Cases at Fine Temporal Scales: Correlations Across Twenty Sewersheds in North Carolina

PWAT-D-23-00083R1

Dear Ms. Christensen,

We are pleased to inform you that your manuscript 'Using Detrending to Assess SARS-CoV-2 Wastewater Loads as a Leading Indicator of Fluctuations in COVID-19 Cases at Fine Temporal Scales: Correlations Across Twenty Sewersheds in North Carolina' has been provisionally accepted for publication in PLOS Water.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Water.

Best regards,

Vikram Kapoor, Ph. D.

Academic Editor

PLOS Water

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Reviewer Comments (if any, and for reference):