Peer Review History

Original SubmissionJune 14, 2021
Decision Letter - Dong Keon Yon, Editor
Transfer Alert

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PONE-D-21-19497An Adaptive, Asymptomatic SARS-CoV-2 Workforce Screening Program Providing Real-Time, Actionable Monitoring of the COVID-19 Pandemic.PLOS ONE

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PLOS ONE

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“SSC, PGT, and RJW are partially supported by the National Institutes of Health, under CEIRS contract no. HHSN272201400006C, SSC under CIVIC contract no.75N93019C00052 and PGT under R01 AI121832. The described work was partially supported by the American Lebanese Syrian Associated Charities (ALSAC).”

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7. One of the noted authors is a group or consortium [L Kercher TP Fabrizio J Franks P Freiden B Sharp, RC Mettelman A Springer M Mori SR Dennis Y Sun Y Su V Rajagopal J Massey PE Mead MP Gann Z Gu J Brazelton de Cardenas B Mathieson K Lahmon S Suganda]. In addition to naming the author group, please list the individual authors and affiliations within this group in the acknowledgments section of your manuscript. Please also indicate clearly a lead author for this group along with a contact email address.

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Additional Editor Comments:

I am sorry for the delay response of your paper due to the absence of an your assigning editor. Do the revision quickly please.

[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: No

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?

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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: An Adaptive, Asymptomatic SARS-CoV-2 Workforce Screening Program

Editorial comments

• Lines 65-66: Local and regional containment strategies are important to allow safe reopening of the country [10]. Which country? Or do you mean countries?

• Line 66: …. …regional containment strategies are important to allow safe reopening of the country [10]. Line 66: SARCoV-2 has been described in fully vaccinated individuals. There is a jump from one idea to the next. There is a need for connector between these two sentences.

• Line 70: SARS-CoV-2 PCR-based.

• Line 71: turnaround times aimed at asymptomatic

• Line 154: ….CoV 2 PCR testp positive….

• Line 164: “One in two”, may be half?

General comments

• According to Line 7, the aim of this paper is to “describe a sustained and adaptable SARS-CoV-2 PCR based testing program with rapid turnaround aimed at asymptomatic workforce members, as part of a multilayered institutional COVID-19 mitigation strategy at a pediatric specialty hospital that treats immunocompromised patients”. This is not a sufficient aim for a paper. For the paper to be impactful, it should not only describe but also critically assess or analyze the program.

• The methods section, as currently presented, does not describe the methods used in the paper or study. Rather, the section describes the Asymptomatic SARS-CoV-2 Workforce Screening Program as part of a wider Covid-19 management program. Therefore, the section should correctly be given the heading Program description. On the contrary, the results section presents various statistical measures as part of the evaluation of the program. The methods used in the calculation of the statistical parameters and the overall analysis or evaluation of the program should be presented in the methods section. How were asymptomatic workers identified, how were vaccinated employees identified? How was sequencing conducted? How was follow-up conducted?

• The paper has some time-to-event data in form of “median time from second vaccine dose to positive SARS CoV-2 PCR test. How was this assessed? Was a survival analysis conducted

• Why are demographic data only provided for vaccinated employees?

• Is it possible to tabulate some of the information provided in the results section?

• In the results section, vaccination results are presented by name or type of vaccine. Is it not necessary to discuss the results by type of vaccine.

Reviewer #2: This is excellent paper. I read it with great interest and I have no further comments.

#1. Update your paper's reference on the latest date.

#2. Please discuss about the vaccination program (booster or and so on) breifly.

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Reviewer #1: Yes: Wells Utembe

Reviewer #2: No

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Attachments
Attachment
Submitted filename: An Adaptive, Asymptomatic SARS-CoV-2 Workforce Screening Program.docx
Revision 1

April 9, 2022

Re: Response to reviewer comments received March 21st , 2022, for manuscript PONE-D-21-19497: “An Adaptive, Asymptomatic SARS-CoV-2 Workforce Screening Program Providing Real-Time, Actionable Monitoring of the COVID-19 Pandemic.”

We thank the reviewers and editors for their time and insightful comments (noted in italics). Please find below a point-by-point response.

Editorial comments

Lines 65-66: Local and regional containment strategies are important to allow safe reopening of the country [10]. Which country? Or do you mean countries?

Response: We meant countries. This has been corrected.

Line 66: …. …regional containment strategies are important to allow safe reopening of the country [10]. Line 66: SARCoV-2 has been described in fully vaccinated individuals. There is a jump from one idea to the next. There is a need for connector between these two sentences.

Response: This section has been edited as follows:

“Testing played a significant role in pandemic containment during the height of the pandemic, through phases of sporadic cases or clusters, even as overall transmission has declined, especially in areas with uneven geographic vaccine coverage [9]. Specifically, the establishment of asymptomatic testing programs to mitigate COVID-19 have been used in both healthcare and not healthcare settings. While SARS-CoV-2 has been described in fully vaccinated individuals [2, 10-13], the role and value of asymptomatic testing in this group is not well described, although, the US CDC has recommended halting this workplace practice [14]. In addition to widespread available testing, local and regional containment strategies are important to allow safe reopening of countries [15].”

Line 70: SARS-CoV-2 PCR-based.

Response: This has been corrected.

Line 71: turnaround times aimed at asymptomatic

Response: This has been corrected.

Line 154: ….CoV 2 PCR testp positive….

Response: This has been corrected.

Line 164: “One in two”, may be half?

Response: This has been modified.

General comments

According to Line 7, the aim of this paper is to “describe a sustained and adaptable SARS-CoV-2 PCR based testing program with rapid turnaround aimed at asymptomatic workforce members, as part of a multilayered institutional COVID-19 mitigation strategy at a pediatric specialty hospital that treats immunocompromised patients”. This is not a sufficient aim for a paper. For the paper to be impactful, it should not only describe but also critically assess or analyze the program.

Response: We have more than described the program. We have shown the feasibility of an asymptomatic SARS-CoV-2 workforce screening program, its impact on detection of asymptomatic infections and resultant potential days of transmission averted underscoring its values as an important component of a multifaceted risk mitigation strategy and its iterative adaption based on the pulse of the pandemic. The last paragraph of the introduction now reads:

“We describe a sustained and adaptable SARS-CoV-2 PCR-based screening program with rapid turnaround times, as part of a multilayered institutional COVID-19 mitigation strategy at a pediatric specialty hospital that treats immunocompromised patients and characterize the course of asymptomatic infections. We show the impact of the program in terms of number of asymptomatic infections detected and potential days of transmission, averted. This program spanned the initiation of a vaccination campaign allowing for the detection of SARS-CoV-2 in 16 asymptomatic, fully vaccinated employees and demonstrates a robust and flexible testing paradigm as a critical component of a multifaceted approach to disease control that can be deployed in future potential outbreaks.”

The methods section, as currently presented, does not describe the methods used in the paper or study. Rather, the section describes the Asymptomatic SARS-CoV-2 Workforce Screening Program as part of a wider Covid-19 management program. Therefore, the section should correctly be given the heading Program description. On the contrary, the results section presents various statistical measures as part of the evaluation of the program. The methods used in the calculation of the statistical parameters and the overall analysis or evaluation of the program should be presented in the methods section.

Response: A methods section has been included with this information and the content describing the program was moved to a section titled “Program description” as suggested by the reviewer.

How were asymptomatic workers identified, how were vaccinated employees identified?

Response: Initially, we had trained screeners asking for symptoms upon employees entering the restricted access points to campus. Eventually, an app was developed, and most employees adopted the use of the app to self-screen for symptoms daily. In addition, Occupational Health would ask presence or absence of symptoms in those who tested positive for SARS-CoV-2.

How was sequencing conducted?

Response: A methods section has been included with information related to SARS-CoV-2 PCR testing and sequencing.

How was follow-up conducted?

Response: The following sentence was added in the Program description:

“Follow up of all employees testing positive for SARS-CoV-2 was performed through weekly phone calls during the isolation period until employee met CDC criteria to return to work.”

The paper has some time-to-event data in form of “median time from second vaccine dose to positive SARS CoV-2 PCR test. How was this assessed? Was a survival analysis conducted?

Response: A formal survival analysis was not done given the relatively small number of events. Data shown is using descriptive statistics.

Why are demographic data only provided for vaccinated employees?

Response: The following table has been added including information on unvaccinated employees.

Asymptomatic screening

N=414 Symptomatic/ Post exposure testing*

N=406

Unvaccinated

N=398 Vaccinated

N=16 Unvaccinated

N=401 Vaccinated

N=5

Age (median, range) 41.5 (18.75-72.26) 55.74 (25.51- 65.62) 40.39 (18.06-71.53) 43.33 (28.65 ~ 53.46)

Gender

Female

Male

242 (60.8%) 8 (50%) 283 (70.57%) 4 (80%)

156 (39.2%) 8 (50%) 118 (29.43%) 1 (20%)

Race

Black

White

Asian

Hispanic

Others

189 (47.73%) 4 (25%) 104 (26.53%) 1 (20%)

162 (40.91%) 12 (75%) 243 (61.99%) 3 (60%)

16 (4.04%) 0 10 (2.55%) 0

17 (4.29%) 0 24 (6.12%) 0

12 (3.03%) 0 11 (2.81%) 1 (20%)

Days from second vaccine dose (median, range) NA 53 (14-94) NA 78 (63-92)

Type of Vaccine

Pfizer-BioNTech

Moderna

NA 15 (93.75%) NA 5 (100%)

NA 1 (6.25%) NA 0

*Includes testing due to onset of symptoms consistent with COVID-19 or after exposure to someone with COVID-19

Is it possible to tabulate some of the information provided in the results section?

Response: A table has been added with the requested demographic information.

In the results section, vaccination results are presented by name or type of vaccine. Is it not necessary to discuss the results by type of vaccine?

Response: We appreciate reviewer’s comment. All SARS-CoV-2 cases in fully vaccinated employees described in the manuscript were among employees who received an mRNA vaccine, with only one receiving Moderna. The main reason is that Pfizer-BioNTech was the vaccine that was widely available to our institution and does not reflect any differences related to vaccine effectiveness.

Attachments
Attachment
Submitted filename: Response to reviewers.docx
Decision Letter - Dong Keon Yon, Editor

An Adaptive, Asymptomatic SARS-CoV-2 Workforce Screening Program Providing Real-Time, Actionable Monitoring of the COVID-19 Pandemic.

PONE-D-21-19497R1

Dear Dr. Hijano,

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,

Dong Keon Yon, MD, FACAAI

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Congratulation on your mesmerizing paper.

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

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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

**********

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

Reviewer #1: 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 #1: Yes

**********

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

**********

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 paper can now be accepted as the authors have restructured the paper and addressed all my concerns.

**********

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: No

Formally Accepted
Acceptance Letter - Dong Keon Yon, Editor

PONE-D-21-19497R1

An adaptive, asymptomatic SARS-CoV-2 workforce screening program providing real-time, actionable monitoring of the COVID-19 pandemic.

Dear Dr. Hijano:

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.

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Dong Keon Yon

Academic Editor

PLOS ONE

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