PONE-D-21-27196Remdesivir in combination with dexamethasone for patients hospitalized with COVID-19: a retrospective multicenter studyPLOS ONE

Dear Dr. Gressens,

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Muhammad Adrish, MD, MBA, FCCP, FCCM

Academic Editor

PLOS ONE

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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: Yes

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: No

Reviewer #2: No

Reviewer #3: 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

Reviewer #3: 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: Thanks for sending the paper for review. This is a well written draft. My specific comments are:

Line 42: Abstract: You can describe how you performed propensity score matching as you can add another 49 words.

Line 44-51: Methods: Please mention somewhere that you analyzed and presented data of 180 matched patients

Line 100: Informed consent can be taken from the relatives of the patients; I am not sure whether we could use data without any kind of consent. Please clarify this

Looking forward to a revised version.

Reviewer #2: Gressens et al report here the effect of the combination of dexamethasone + remdesivir compared to dexamethasone alone in hospitalized French patients with COVID-19 pneumonia. The authors state that in hospitalized patients with COVID-19 pneumonia receiving low-flow oxygen the addition of remdesivir to dexamethasone was not associated with shorter hospitalization or lower in-hospital mortality but may have reduced the combined outcome of death and transfer to the ICU.

The manuscript is enticing because it brings new light to the positive effect of remdesivir on COVID-19 infection. Results on this topic have been contradictory so far.

This reviewer can raise some points needing clarification by the authors.

Major points

1.Why different mortality outcomes were selected in this study: In-hospital death, in-hospital death and/or transfer to the ICU, in-hospital death and/or endotracheal intubation (Page 9, lines 134-140)

2.”In-hospital death rates were 8.9% and 20%, with and without remdesivir (p=0.06)!. This is a not-significant trend (p>0.05). perhaps due to the low number of patients included in the study (Page 16, line 275). This not-significant comparison might be confusing for the reader and perhaps it might be deleted from the abstract

Minor points

1. Could you actualize the worlwide COVID-19 information to November 2021? (Page 5, lines 59-60)

2. Could you explain further the expression “matched without replacement, using a caliper of 0.10 the standard deviation of the propensity…” (Page 19, lines 159-160). It is rather confusing in this form.

3. Could you change “endotracheal intubation (ETI)” to “mechanical ventilation”?

4. Could you change “OMS scale” to “WHO scale” in Table 1?

Reviewer #3: The manuscript by Gressens et al is concise and well-written. Although several retrospective studies of the same kind have been published this study adds another dataset to the our understanding of the potential benefits of remdesivir treatment.

Minor: The authors should mention the pinetree study in the discussion section.

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Reviewer #1: Yes: Mahbub-Ul Alam

Reviewer #2: No

Reviewer #3: No

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Remdesivir in combination with dexamethasone for patients hospitalized with COVID-19: a retrospective multicenter study

PONE-D-21-27196R1

Dear Dr. Gressens,

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,

Maria Elena Flacco, M.D.

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

Reviewer #3: 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: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #2: I am pleased with the revised version of this manuscript. The authors have answered all the queries raised by me and by the other reviewers . In my opinion this manuscript now it might be accepted in PLOS ONE

Reviewer #3: Comments have been adressed. No additional comments. The manuscript is well written and concise. The manuscript merits publication.

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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: VICTOR ASENSI

Reviewer #3: No