Peer Review History

Original SubmissionMarch 26, 2024
Decision Letter - Giuseppe Di Martino, Editor

PONE-D-24-10892High-frequency PCR-testing as a powerful approach for SARS-CoV-2 surveillance in the field of critical infrastructure: a longitudinal, retrospective study in a German tertiary care hospitalPLOS ONE

Dear Dr. Fischer,

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Giuseppe Di Martino

Academic Editor

PLOS ONE

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Additional Editor Comments:

The paper is well written and clearly presented.

Major observations:

- In Methods section Authors should describe how data was presented and how analysis was conducted;

- Abput reinfections, Authors should report the incidence and in discussion section Authors should compare this result with published literature;

- Authors should also discuss how vaccination campaign impacted the surveillance.

- I suggest also to discuss the vaccination efficacy

[Note: HTML markup is below. Please do not edit.]

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: Partly

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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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: Overall, I believe that this is a well conducted study and a well written manuscript, which deserves to be published in the peer-reviewed evidence-based literature. As such, I have recommended that it be published with a couple of minor revisions.

I would greatly appreciate if the authors could please address the following concerns:

1. Most importantly, unless I am mistaken, I believe that your conclusion statement should read as "High-frequency PCR-testing is a powerful tool concerning SARS-CoV-2 surveillance in the field of critical infrastructure. In addition, our data show that SARS-CoV-2 RNA is detectable for longer in elderly individuals compared to younger ones" as opposed to "...for longer in younger individuals compared to elderly." After all, Figure 6 clearly shows that older individuals had lower CT values (higher viral loads) for a greater number of days than younger ones, and this phenomenon is also mentioned in your Discussion section.

2. Please fix the following minor grammatical error and clarify the following:

-"high-frequency PCR-testing" in place of "high-frequent PCR-testing" - in the Abstract section.

-"November 18, 2020" in place of "November 18th" for timing of when testing became mandatory - in the Results section.

Reviewer #2: The manuscript is meticulously crafted and well-organized, drawing from a sizable dataset of approximately 285,000 oral swab samples collected from 3,421 healthcare workers. It explores the impact of frequent PCR testing for SARS-CoV-2 surveillance during the COVID-19 pandemic. The statistical methods employed are robust and thoroughly documented, ensuring the reliability of the findings. The manuscript effectively communicates complex findings in an accessible manner, providing clear explanations for the study's choices and enhancing the overall clarity of the presentation.

The manuscript effectively utilizes a large dataset to address a critical issue in healthcare. While it is statistically robust and well-written, its retrospective design and setting-specific conclusions may limit its broader applicability. A more thorough discussion of potential biases, including the impact of external factors (e.g., changes in public health policies or vaccine uptake) on the results, would strengthen the manuscript.

The study cites 3,421 healthcare workers, while the Heart and Diabetes Center (HDZ) has around 2,500 employees. Could you clarify if the study included additional staff members beyond the healthcare workers, or if there might be another explanation for the difference in these figures?

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Reviewer #1: No

Reviewer #2: Yes: Lawrence Annison

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Revision 1

Response to reviewers

Additional Editor Comments:

The paper is well written and clearly presented.

Major observations:

- In Methods section Authors should describe how data was presented and how analysis was conducted;

Thanks, we added the information, that we used GraphPad Prism 10.1.2 for the visualization and statistical analysis of the data.

- About reinfections, Authors should report the incidence and in discussion section Authors should compare this result with published literature;

Thanks for this valuable comment. We reported the incidence within the “result” section (Fig. 4) and already compared our values with published literature. Based on your comment, we now calculated two different reinfection-incidences and supplemented Fig. 4 in this regard: the incidence per tested individual (Fig. 4, left Y-axis) and the incidence per total employees (Fig. 4, right Y-axis). Due to the low rate of secondary- and third reinfections, the latter was only considered for the “1st reinfection cohort”.

- Authors should also discuss how vaccination campaign impacted the surveillance.

We have now discussed this aspect in the last section of the discussion.

- I suggest also to discuss the vaccination efficacy

We have now also discussed this aspect in the last section of the discussion.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

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: Overall, I believe that this is a well conducted study and a well written manuscript, which deserves to be published in the peer-reviewed evidence-based literature. As such, I have recommended that it be published with a couple of minor revisions.

I would greatly appreciate if the authors could please address the following concerns:

1. Most importantly, unless I am mistaken, I believe that your conclusion statement should read as "High-frequency PCR-testing is a powerful tool concerning SARS-CoV-2 surveillance in the field of critical infrastructure. In addition, our data show that SARS-CoV-2 RNA is detectable for longer in elderly individuals compared to younger ones" as opposed to "...for longer in younger individuals compared to elderly." After all, Figure 6 clearly shows that older individuals had lower CT values (higher viral loads) for a greater number of days than younger ones, and this phenomenon is also mentioned in your Discussion section.

Thank you very much for this important suggestion. We have changed the sentence.

2. Please fix the following minor grammatical error and clarify the following:

-"high-frequency PCR-testing" in place of "high-frequent PCR-testing" - in the Abstract section.

-"November 18, 2020" in place of "November 18th" for timing of when testing became mandatory - in the Results section.

Thank you for your comments, we have made the changes.

Reviewer #2: The manuscript is meticulously crafted and well-organized, drawing from a sizable dataset of approximately 285,000 oral swab samples collected from 3,421 healthcare workers. It explores the impact of frequent PCR testing for SARS-CoV-2 surveillance during the COVID-19 pandemic. The statistical methods employed are robust and thoroughly documented, ensuring the reliability of the findings. The manuscript effectively communicates complex findings in an accessible manner, providing clear explanations for the study's choices and enhancing the overall clarity of the presentation.

The manuscript effectively utilizes a large dataset to address a critical issue in healthcare. While it is statistically robust and well-written, its retrospective design and setting-specific conclusions may limit its broader applicability. A more thorough discussion of potential biases, including the impact of external factors (e.g., changes in public health policies or vaccine uptake) on the results, would strengthen the manuscript.

Thanks a lot for your advice. We have expanded the discussion to include these aspects.

The study cites 3,421 healthcare workers, while the Heart and Diabetes Center (HDZ) has around 2,500 employees. Could you clarify if the study included additional staff members beyond the healthcare workers, or if there might be another explanation for the difference in these figures?

Thanks for this important demand. The general number of employees at our hospital is around 2,500. The difference between individuals screened by PCR and employees is explainable by a regular staff turnover of employees per month accumulating over the 2.5 year period. We added this aspect to the manuscript.

Attachments
Attachment
Submitted filename: Response to reviewers.docx
Decision Letter - Giuseppe Di Martino, Editor

High-frequency PCR-testing as a powerful approach for SARS-CoV-2 surveillance in the field of critical infrastructure: a longitudinal, retrospective study in a German tertiary care hospital

PONE-D-24-10892R1

Dear Dr. Bastian Fischer,

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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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. 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.

Kind regards,

Giuseppe Di Martino

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: (No Response)

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

Reviewer #2: (No Response)

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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 #2: (No Response)

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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: (No Response)

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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 #2: (No Response)

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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: Yes: LAWRENCE ANNISON

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Formally Accepted
Acceptance Letter - Giuseppe Di Martino, Editor

PONE-D-24-10892R1

PLOS ONE

Dear Dr. Fischer,

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

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Giuseppe Di Martino

Academic Editor

PLOS ONE

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