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PONE-D-21-09664

Improved outcomes over time for adult COVID-19 patients with acute respiratory distress syndrome or acute respiratory failure

PLOS ONE

Dear Dr. Yeates,

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PLOS ONE

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[I have read the journal's policy and the authors of this manuscript have the following competing interests:

Alpesh Amin reported serving as PI or co-I of clinical trials sponsored by NIH/NIAID, NeuroRx Pharma, Pulmotect, Blade Therpeutics, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, OctaPharma, Fulcrum Therapeutics, Alexion. He has served as speaker and/or consultant for BMS, Pfizer, BI, Portola, Sunovion, Mylan, Salix, Alexion, AstraZeneca, Novartis, Nabriva, Paratek, Bayer, Tetraphase, Achogen LaJolla, Millenium, HeartRite, Aseptiscope, Sprightly.

Ninh Nguyen reported serving as a speaker for Olympus and Endogastric Solutions.].

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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

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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: The authors describe outcomes over the first six months of the pandemic for adult COVID-19 patients in the US who developed acute respiratory distress syndrome or acute respiratory failure. This study describes the outcomes of a large cohort with COVID-19 ARDS or ARF and the subsequent decrease in cost, mechanical ventilation, and mortality over the first 6 months of the pandemic in the US. This is interesting and valuable to see the result in gradual reductions of mortality rates and costs with improvement treatment strategies and skills because no other research like this has been performed.

Are there any other factors that decreased the case mortality rate other than the improvement of medical technology? Reducing the burden on medical staff may be one of the factors that lowered the case mortality rate.

Is it possible to find out how many COVID-19 patients of all inpatients? If the authors knew the proportion of COVID-19 patients admitted to the facilities, the authors could infer how much burden has been placed on the medical facilities.

Reviewer #2: Eric O Yeates, et al. claims that mortality, cost, and the rate of mechanical ventilation of patients of COVID-19 with ARDS or ARF during March-May 2020 were significantly decreased compared with those during June-July 2020 in the USA. I am one of clinicians who have treated hundreds of hospitalized patients with COVID-19 in the country other than the US. The author’s statement is compatible with my clinical impression in my country. I agree with the most of their opinion. They focused on the patients with COVID-19 who experienced ARF or ARDS. Data focusing on the population are novel and interesting. However, there are a lot of limitations in the research, as they mention. Discussion mostly consisted of their assumption because they did not directly analyze the association between each factor (respiratory strategies, corticosteroid, or anti-viral medications) and the outcome. They only compared trends of March-May to those of June-July. It is the biggest limitation.

Major comments

1. As I pointed out, the author did not directly analyze the association between each factor and the outcome, such as mortality, ventilation-rate and the cost. It is the biggest limitation. So, they should mention as one of the study limitations.

2. Page 8 Line 131, I think that mortality rates in patients not requiring mechanical ventilation were similar over time, although the statistical significance was not shown. None-statistical significance dose not mean the similar. For example, I think that mortality in March (12.1%) is not similar to that in July (4.5%). Please revise the sentence.

3. Page 8 Line 147 to Line148, the authors should include corticosteroid into one of novel therapeutics. Corticosteroid is the most effective therapeutic agent against COVID-19. It has strong evidence.

Minor comments

1. Page 4 line 48, I think that the COVID-19 virus is correct medical jargon. SARS-CoV-2 is appropriate.

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Reviewer #1: No

Reviewer #2: No

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Improved outcomes over time for adult COVID-19 patients with acute respiratory distress syndrome or acute respiratory failure

PONE-D-21-09664R1

Dear Dr. Yeates,

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,

Robert Jeenchen Chen, MD, MPH

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 #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

**********

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

Reviewer #1: Yes

Reviewer #2: 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

Reviewer #2: 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

Reviewer #2: 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: (No Response)

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 #1: No

Reviewer #2: No