PONE-D-20-19154

ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS

PLOS ONE

Dear Dr. Baykal,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The data presented are interesting. However, the manuscript has several major flaws which require careful attention. All of these are outlined in the comments to the authors. I recommend the authors to fully address these comments.

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We look forward to receiving your revised manuscript.

Kind regards,

Nades Palaniyar, MSc., PhD.

Academic Editor

PLOS ONE

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2. Please include a copy of Table 1 which you refer to in your text on page 6.

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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: Partly

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

Reviewer #1: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: 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: No

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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: Recent research clearly demonstrates that a delicate balance exists between protective immune responses that effectively clear SARS-CoV-2 infections with mild symptoms, versus overly exuberant immune responses that are likely to worsen disease outcome. Thus, understanding the nature of immune responses elicited by SARS-CoV-2 infection remains an important area of study. In this manuscript, Akgun et al. perform proteomic analysis of nasopharyngeal swabs from SARS-CoV-2 positive and negative patients. The authors report an enrichment in proteins associated with neutrophil degranulation/NETosis. The data itself is interesting however, the manuscript is poorly written and lacks several important details (including a critical data Table). These issues should be carefully addressed to improve the manuscript.

Major Comments:

1. The authors must provide more information about the participants in this study. This should include demographics (age, sex, etc.) as well as data pertaining to when swabs were taken (relative to onset of symptoms for example) and ideally, clinical severity. Were the SARS-CoV-2-negative participants healthy, or did they have some other ailment?

2. Table 1 (noted on line 134) appears to be missing from the manuscript file. This table contains the central data of the manuscript and its absence makes reviewing very difficult.

3. Supplementary tables should be called out in the text.

4. The discussion is too long and unfocused. For example, the authors spend considerable space discussing the role of NETosis in autoimmunity, which is completely tangential and should be removed. Instead, the authors should focus specifically on how their data fits in with reported characteristics of SARS-CoV-2 infections - specifically the role of neutrophils/NETs.

5. The discussion lacks balance. The authors seem to favor the hypothesis that their protein signature (or neutrophil degranulation/NETosis in general) is problematic, but provide not evidence to support that notion. It is certainly possible that dysregulated neutrophil responses could be pathogenic, but a balanced response might also be protective. Since the results presented by the authors is entirely descriptive, they should endeavor to provide a more balanced discussion of their interpretation.

6. The title of the manuscript is misleading. The authors should a difference between the proteomic profiles of infected vs. uninfected individuals. Thus, the fact that pathways are "altered" compared to SARS-CoV-2 negative participants is not surprising. A more descriptive title would be more appropriate. For example "Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients"

Minor comments:

1. The manuscript needs to be thoroughly edited for English language/grammar.

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Reviewer #1: No

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Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients

PONE-D-20-19154R1

Dear Dr. Baykal,

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,

Nades Palaniyar, MSc., PhD.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments: