PONE-D-22-35551Assessment of antibody dynamics and neutralizing activity using serological assay after SARS-CoV-2 infection and vaccinationPLOS ONE

Dear Dr. Tabe,

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Etsuro Ito

Academic Editor

PLOS ONE

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https://www.nature.com/articles/s41598-022-19073-z?code=86adafd0-3d6f-4c5a-a73e-8355546cc298&error=cookies_not_supported

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“This research was partially supported by Japan Agency for Medical Research and Development under Grant Number JP20fk0108472 to TN and by Japan Society for the Promotion of Science Grants-in Aid for Scientific Research under Grant Number 22K15675 to ST.”

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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: 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: [General Comments]

The authors showed that antibody dynamics and neutralizing activity following COVID-19 vaccination/ infection among patients, HCWs. Although the study poluation and back ground seems unique, there're some points to be revised. And the manuscript is redundunt with too many figures. Simplify is also required.

[Specific Comments]

1. Introduction

The PECO of the study is unclear. 'Investigate the serological kinetics' seems to be vague.

2. Method

Line 105; Should clalify the number of community acquired/ nosocomial COVID-19 case.

Line 106; Should describe the breakdown of HCWs (i.e. Nurses N= , doctors N=, Lab technician N= ...)

3. Result

The first half of result is overlapped with table1. Table 1 should be deleted. Or simplify the manuscript including quotation of Table1.

For Figure 2A, Plot of each group (S and M) should combined.

For Figure 2B, Plot of each group (S and M) should combined.

Number of the categolized study population shoud be noted on the figure. (i.e. number of the subject in N-IgG pisitive & COVID-19 Medical History positive in Figure 3A.)

Most of figure legends are overlapped with each figures. Delete overlapped description in the manuscript.

4. Discussion

The authors add the thought, or plan, of potential for clinical use in real world according to the result of the study.

Reviewer #2: PONE-D-22-35551_reviewer

This is an important study to compare the three different antibody analysis methods and their kinetics among COVID-19 cases and HCWs after 2-dose vaccination, using authentic virus neutralization assay as a reference. Please consider to revise the manuscript, based on the comments listed below.

Major comments

Abstract

L 47-49: Does this sentence mean that “low titer of” anti-S IgG or sVNT causes breakthrough infection? The meaning is a little bit difficult to understand.

Overall, please consider to revise the abstract accordant with the revision of the main text, tables and figures.

Introduction

The aim of this study is not matched with the conclusion. Please revise in accordance with the other contents of the manuscript.

Material and Methods

L 109-110: Immunosuppressive agents are commonly used to treat COVID-19 itself. Does this study exclude COVID-19 patients treated with immunosuppressive agents such as corticosteroid or other biologic agents? Or are the patients using immunosuppressive agents for their underlying diseases before contracting COVID-19 excluded ?

It is unclear how the authors collected the history of contracting COVID-19 from the HCWs and how they identified infection with delta variant or other variants.

L120: Please describe the detailed material and methods of the long-term evaluation study.

L170: The meaning of “When experiments involved more than two groups” is difficult to understand.

L175: What is the longitudinal analysis? Is it same as “long-term evaluation study”? Please clarify the meaning.

Results

Overall, description about the methods seems mixed in the Result part. For example, L182-183, L214-221, L240-245.

L269-272: As pointed out in the Material and Methods part, please clarify the methods to identify the past history of COVID-19 of HCWs and type of variants, and revise the description if necessary.

Discussion

L294-296: Relatedness with the former sentences in L292-294 is a little bit confusing. Do the authors intend to say the authentic virus neutralization activity increases more slowly/weakly than anti-S antibody and/or sVNT?

L328: the distribution of age in the Groups should be written in the Result part.

L331-333: The conclusion is not matched with the aim of the study described at the end of the Introduction part (investigation or serologic kinetics).

The authors conclude that usefulness of titers of anti-S IgG and sVNT as surrogate markers of neutralizing capacity is limited, But as an experiment, concordance of titers of anti-S IgG and sVNT with authentic neutralization assay seems acceptable, even though some cases show discrepancy. Do the authors intend to describe the insufficiency of the three markers to predict the ability to prevent infection?

Minor comments

L114: SpO2 should be written with small "2".

L133: AU/ml should be written as AU/mL.

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Reviewer #1: No

Reviewer #2: No

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Assessment of antibody dynamics and neutralizing activity using serological assay after SARS-CoV-2 infection and vaccination

PONE-D-22-35551R1

Dear Dr. Tabe,

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,

Etsuro Ito, Ph.D.

Academic Editor

PLOS ONE

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

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

Reviewer #1: Yes

Reviewer #2: 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 #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 #1: Yes

Reviewer #2: 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: The authors revised well according to the recommendations. The authors should conduct similar investigations.

Reviewer #2: The authors revised the manuscript following the previous suggestions and comments appropriately, and made the manuscript more clearly understandable.

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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: Yuji Hirai

Reviewer #2: No

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