PONE-D-23-34297Analysis of prognostic factors in critically ill patients with COVID-19PLOS ONE

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Benjamin M. Liu, MBBS, PhD, D(ABMM), MB(ASCP)

Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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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: No

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

Reviewer #1: Yes

Reviewer #2: No

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: 1. There are some good review articles summarizing research status quo on risk factors etc IL-6. But this manuscript failed to cite these papers. The pathogenesis of SARS-CoV-2 in cytokine storm and ARDS as well as challenges of testing and interpretating these biomarkers should be discussed based on the following 2 references.

Role of Host Immune and Inflammatory Responses in COVID-19 Cases with Underlying Primary Immunodeficiency: A Review. J Interferon Cytokine Res. 2020 Dec;40(12):549-554. doi: 10.1089/jir.2020.0210. PMID: 33337932; PMCID: PMC7757688.

Clinical significance of measuring serum cytokine levels as inflammatory biomarkers in adult and pediatric COVID-19 cases: A review. Cytokine. 2021 Jun;142:155478. doi: 10.1016/j.cyto.2021.155478. Epub 2021 Feb 23. PMID: 33667962; PMCID: PMC7901304.

2. The authors should add more information on the methods of detecting SARS-CoV-2 and the biomarkers and other indexes under investigation.

3. Are statistical analysis two tailed or one tailed?

Reviewer #2: Summary of the research: The study aims to predict the mortality in critically ill COVID - 19 patients. The authors have meticulously collected data of 201 patients admitted in the ICU. It has been concluded that APACHE II scores , prone positioning and neuromuscular blocking agents are associated with ICU mortality among COVID-19 patients. The manuscript has been written in an intelligible fashion.

Major issues:

Issue 1: Statistical analysis

The protocol used to select the variables for uni-variate and multivariate regression analysis has not been clearly defined. The authors can perhaps refer to the reference 9 cited in the manuscript for improving the statistical analysis especially the regression analyses and also the analysis of the continuous variables.

1a. The authors have concluded that APACHE II score, emerged as significant predictor in multivariate analysis. But in table 1, the mean APACHE II score in the survivor and non survivor group and all the cases appear similar (28.8 (7.9%), 29.4 (8.2%), 29.1(8.0%)). So the conclusion regarding the APACHE II score being a predictor is not statistically sound.

1b. The authors have discussed that the duration of the mechanical ventilation (MV) is inversely related to the mortality risk. Here the duration is not specified. If we look at the table 1, the means in the survivor and non survivor group and all the cases again appear to be the same (11.2 (9.1%), 11.2 (8.8%) and 11.2 (9%)). So what does this conclusion mean?

Minor issue

There is an incomplete sentence where the reference 19 is cited.

The data may perhaps reveal better patterns if more sound regression analysis is conducted. Looking forward to the improved version of the data analysis and hence better conclusions in the manuscript.

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Reviewer #1: No

Reviewer #2: Yes: Dr Prasanna N Bhat

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Analysis of prognostic factors in critically ill patients with COVID-19

PONE-D-23-34297R1

Dear Dr. Czaban,

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.

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Kind regards,

Benjamin M. Liu, MBBS, PhD, D(ABMM), MB(ASCP)

Academic Editor

PLOS ONE

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