Peer Review History

Original SubmissionAugust 9, 2021
Decision Letter - Gheyath K. Nasrallah, Editor

PONE-D-21-25774SARS-CoV-2 Seroepidemiology in ChildrenPLOS ONE

Dear Dr. Hourigan,

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Gheyath K. Nasrallah

Academic Editor

PLOS ONE

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“The Virginia Department of Health provided funding for this study. The Virginia Department of Health, in conjunction with the authors of this manuscript, were involved in study design, the writing of the report and the decision to submit the paper for publication. The Virginia Department of Health were not involved in collection, analysis or interpretation of the data.  Research reported in this publication was also supported in part by the National Institute of Child Health and Human Development under Award Number K23HD099240 (Hourigan). Research reported in this publication was also supported in part via a subcontract from the parent award by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR003015 (Hunter, Sun, Bruce). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health”

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“The Virginia Department of Health provided funding for this study. The Virginia Department of Health, in conjunction with the authors of this manuscript, were involved in study design, the writing of the report and the decision to submit the paper for publication. The Virginia Department of Health were not involved in collection, analysis or interpretation of the data.  Research reported in this publication was also supported in part by the National Institute of Child Health and Human Development under Award Number K23HD099240 (Hourigan). Research reported in this publication was also supported in part via a subcontract from the parent award by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR003015 (Hunter, Sun, Bruce). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

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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

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Reviewer #1: The authors performed seroepidemiologic evaluation of SARS-CoV-2 in children in a major metropolitan region of the US. Three FDA approved serology tests were used to assess seroprevalence, Vitros as a primary assay, followed by Orthogonal testing with Siemens and Architect. The observed seroprevalence was higher than what is reported in the literature, I have questions in this regard:

1- Vitros (ortho clinical assay) measures the total antibody to the full spike protein, do you think that the use of Vitros as a primary assay for screening overestimated the seroprevalence in children? as you mentioned in the discussion line 291 “these lower titers levels may represent cross-reactivity to conserved epitopes in benign seasonal human coronavirus” which I agree with. I suggest you cite this paper to support your findings (JCI Insight. 2021;6(4):e144499. https://doi.org/10.1172/jci. insight.144499.).

Reviewer #2: The manuscript by Suchitra K Hourigan and colleagues, titled “SARS-CoV-2 Seroepidemiology in Children"presents a study and test performance data from SARS-CoV-2 spike protein levels in children and adolescents ≤19 years. The work was well-researched, and the authors mined good techniques to evaluate the performance of the assays in detecting SARS-CoV-2 antibodies. There are minor comment:

1#Since the samples were taken in the period July-Octobar 2020. It would be good to plot this months to see which month was most effected to link this date to occasion holidays or schools.

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Reviewer #1: No

Reviewer #2: No

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Revision 1

Response to Reviewers comments

Reviewer #1: The authors performed seroepidemiologic evaluation of SARS-CoV-2 in children in a major metropolitan region of the US. Three FDA approved serology tests were used to assess seroprevalence, Vitros as a primary assay, followed by Orthogonal testing with Siemens and Architect. The observed seroprevalence was higher than what is reported in the literature, I have questions in this regard:

1- Vitros (ortho clinical assay) measures the total antibody to the full spike protein, do you think that the use of Vitros as a primary assay for screening overestimated the seroprevalence in children? as you mentioned in the discussion line 291 “these lower titers levels may represent cross-reactivity to conserved epitopes in benign seasonal human coronavirus” which I agree with. I suggest you cite this paper to support your findings (JCI Insight. 2021;6(4):e144499. https://doi.org/10.1172/jci. insight.144499.).

Thank you for taking the time to review out manuscript. We are in agreement with your insightful comment. We have expanded line 291 to now read “ Future consideration should be given to redefining the lower limit of detection for full spike protein antibody assays as it is possible that these lower titer levels may represent cross-reactivity to conserved epitopes in benign seasonal human coronaviruses [10, 31], with the Ortho Clinical assay overestimating the seroprevalence in children; however it is not possible to confirm this in our study cohort.” and cited the additional paper you recommended (31).

Reviewer #2: The manuscript by Suchitra K Hourigan and colleagues, titled “SARS-CoV-2 Seroepidemiology in Children"presents a study and test performance data from SARS-CoV-2 spike protein levels in children and adolescents ≤19 years. The work was well-researched, and the authors mined good techniques to evaluate the performance of the assays in detecting SARS-CoV-2 antibodies. There are minor comment:

1#Since the samples were taken in the period July-Octobar 2020. It would be good to plot this months to see which month was most effected to link this date to occasion holidays or schools.

Thank you for taking the time to review out manuscript. This is an interesting point which we looked in to further. The positivity rate by month is as follows

July: 0% (0/2)

August: 8.49% (46/542)

September: 10.03% (29/289)

October: 6.34% (13/205)

There was no statistically significant difference in rates by month and therefore we did not think it was worthwhile having a separate figure for this. However, we have added the following to the text, line 222 “There was no significant difference in positivity rate by month in which the study was conducted.”

Attachments
Attachment
Submitted filename: Response to reviewers.docx
Decision Letter - Gheyath K. Nasrallah, Editor

A cross-sectional investigation of SARS-CoV-2 seroprevalence and associated risk factors in children and adolescents in the United States

PONE-D-21-25774R1

Dear Dr. Suchitra K Hourigan

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.

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Kind regards,

Gheyath K. Nasrallah

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Gheyath K. Nasrallah, Editor

PONE-D-21-25774R1

A cross-sectional investigation of SARS-CoV-2 seroprevalence and associated risk factors in children and adolescents in the United States

Dear Dr. Hourigan:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Gheyath K. Nasrallah

Academic Editor

PLOS ONE

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