PONE-D-20-10148

Comparison of participant-collected nasal and staff-collected oropharyngeal specimens for human ribonuclease P detection with RT-PCR during a community-based study

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: 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: No

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: This paper discusses the quality of specimens collected via nasal swabs across multiple axes (participant versus staff collected, delay between specimen collection and testing). Results are very pertinent to influenza as well as other respiratory infection outbreaks.

Overall the study is very clearly described and systematically performed in this paper. There are very minor suggestions:

*Would be helpful to specify the criteria for ARI (line 70)

*Some description regarding what is involved/differences in the anterior vs midturbindate swab collection would be helpful for the non-clinical reader. Consider adding text or a figure if available.

*Would putting the nasal and OP swabs in the same medium conflate results at all? (line 78)

Several pertinent references to previous work are included. Consider citing this paper which shows concordant results in general, but also differs in terms of if the patient self-reports/decides to swab

Goff, Jennifer, et al. "Surveillance of acute respiratory infections using community-submitted symptoms and specimens for molecular diagnostic testing." PLoS currents 7 (2015).

*Some reasoning around the Ct threshold of 38 would be helpful to include

*Paragraph starting at line 125, consider including that differences are statistically significant where appropriate

Note: I am concerned about the data sharing. A broad response was given that all data from the Oregon study will be shared, as well as a comment that "some restrictions may apply". It would be helpful to clarify what the restrictions would be and why. Also, to clarify how long after study completion the data will be made available.

Reviewer #2: This study reports the results of an analysis of specimen quality from self-collected mid-turbinate or nasal swab specimens compared to staff collected oropharyngeal specimens for respiratory virus identification. The manuscript is well written. The methods could be more thoroughly explained, especially with regard to statistical comparisons. I think additional tables/figures would help with the presentation of data and the interpretation of the results. I have additional suggestions by manuscript section, listed below:

Methods

How were confidence intervals calculated? Bootstrap estimates? Were CIs the only statistical means by which differences were tested?

Results

I think some further explanation of the sampling would be helpful or even the study population in general. How many household contacts were swabbed etc? For example: Based on the reported numbers in the results, I assume that there were 376 ARI cases reported in school aged children who were swabbed and then enrolled in the follow up study, it then appears that 712 household members collected two follow up swabs, presumably this includes some households (or individual members) who were only able to collect one specimen. Additionally, the original 376 school aged children are part of the group with self-collected specimens. The same questions would apply to year two. Further there could be clustering of specimen quality by household. So it would be good to have a table or flow chart with the number of school-aged ARI cases that triggered collection, the number of households and household contacts, and the number of complete sets of specimens collected.

Figures

I would separate figures into Ct values and adequacy rather than including both on the same plot. Perhaps make separate panels for each comparison. I also was confused by place Year 1 and Year 2 next to each other in the Figure 1 plot, when the comparison of interest is between

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Reviewer #1: No

Reviewer #2: No

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Comparison of participant-collected nasal and staff-collected oropharyngeal specimens for human ribonuclease P detection with RT-PCR during a community-based study

PONE-D-20-10148R1

Dear Dr. Arnold,

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,

Jeffrey Shaman

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 #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 #2: Yes

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

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 #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 #2: Yes

**********

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 #2: The authors have responded to all critiques from both of the reviewers in an appropriate manner. No further changes are needed.

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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 #2: No