PONE-D-20-23829

Comorbidity and Clinical Factors Associated with COVID-19 Critical Illness and Mortality at a Large Public Hospital in New York City in the Early Phase of the Pandemic (March-April 2020)

PLOS ONE

Dear Dr. Thomas Daniel Filardo,

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.

==============================

ACADEMIC EDITOR: The reviewers have raised a number of points which we believe major modifications are necessary to improve the manuscript, taking into account the reviewers' remarks. Please consider and address each of the comments raised by the reviewers before resubmitting the manuscript. This letter should not be construed as implying acceptance, as a revised version will be subject to re-review.

==============================

Please submit your revised manuscript by Oct 16 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Wisit Cheungpasitporn, MD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please include the date(s) on which you accessed the databases or records to obtain the data used in your study.

3. For studies involving humans categorized by race/ethnicity, age, disease/disabilities, religion, sex/gender, sexual orientation, or other socially constructed groupings, authors should:

1) Explicitly describe their methods of categorizing human populations,

2) Define categories in as much detail as the study protocol allows,

3) Justify their choices of definitions and categories,

4) Explain whether (and if so, how) they controlled for confounding variables such as socioeconomic status, nutrition, environmental exposures, or similar factors in their analysis, and

5) Update outmoded terms and potentially stigmatizing labels to more current, acceptable terminology.

Examples: “Caucasian” should be changed to “white” or “of [Western] European descent” (as appropriate); “XXX victims” should be changed to “patients with XXX.

[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: Yes

Reviewer #2: Yes

Reviewer #3: Partly

Reviewer #4: Partly

Reviewer #5: Yes

**********

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

Reviewer #1: No

Reviewer #2: I Don't Know

Reviewer #3: No

Reviewer #4: I Don't Know

Reviewer #5: Yes

**********

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

Reviewer #3: Yes

Reviewer #4: No

Reviewer #5: Yes

**********

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

Reviewer #4: Yes

Reviewer #5: Yes

**********

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: 1. * Table 1: means for skewed continuous variables (labs) need to be compared using a non-parametric test, such as the Kruskal-Wallis test, not a between-group t-test, which assumes normal distributions.

2. * The authors state “... altered mental status was more common in patients requiring ICU admission (9.6% vs 5.2%, p = 0.16) ..“ When a difference is not significant, the proper way to report it would be something like “ ...altered mental status did not differ significantly between those who did vs did not require ICU admission (9.6% vs 5.2%, p = 0.16). When the p value is > .05 and < 0.10, it may be acceptable to report a difference ‘with a trend level of significance’.

3. It is confusing to have “Supplemental Oxygen” in the table headings in Tables 1 and 2. I would suggesting removing this so it is clear the columns refer to ICU and no-ICU.

4. * Interactions are mentioned in the Method section and are shown in Table 5, but are never discussed in the Results or Discussion.

Reviewer #2: Persons with dementia seem more sensitive to certain types of immune challenge and show higher mortality. Are you able to do any further analysis of the dementia group to suggest reasons for their susceptibility to death from Covid-19?

Given the rapid developments in Covid-19 treatment could the authors make additional comments on the treatment regimes or recent relevant studies.

Reviewer #3: The manuscript entitled ‘Comorbidity and Clinical Factors Associated with COVID-19 Critical Illness and Mortality at a Large Public Hospital in New York City in the Early Phase of the Pandemic (March-April 2020)’ with the aim to assess demographics, comorbid conditions, and clinical factors associated with critical illness and mortality among patients diagnosed with COVID-19 at a public hospital in New York City (NYC) during the first month of the COVID-19 outbreak.

This is an interesting study but the manuscript can be further improved in terms of presentation.

Comments

Abstracts

n= to be inserted for the number of subjects i.e n=127

Methods

Data

For the ‘team of students’, who are the students to be clearly stated.

Data analysis

All statistical tests used in the results section to be clearly stated in statistical analyses section. More information to be provided after this statement ‘testing effect modification by sex, age and comorbidity at the 0.15 level’. The acceptance level of statistical significant to be stated.

Results

Table 1, n= to be employed to indicate total sample. X^2 to be replaced with the actual ‘chi square' symbol.

n(%), N(%) to be placed in the first row. Individual symbol % for individual figures to be omitted. Statistical tests to be clearly denoted in table footnote.

Table 1, under Admission Laboratory Tests, n to be placed after the variable name and not after median (IQR) values (Likewise with Supplemental Table 1). The categorical variables and the continuous variable to be clearly separated with space and indicated with their respective p value. Row alignment for CRP to be improved. Symbol >= to be replaced with symbol ≥ (likewise in Supplemental Table 1). In Supplemental Table 2 <= to be replaced with ≤)

Table 2 & 3 n(%) N(%) to be placed in the first row. Symbol % for individual figure to be omitted. Likewise with Supplemental Table 1 & Supplemental Table 2.

Table 2, NRB to be placed after Oxygen-Non-Rebreather.

Treatment

The sentence ‘The majority of patients received hydroxychloroquine (82.4%)’ to be revised and match the variable name in Table 2. HQ and any HCQ to be clearly defined/denoted in table footnote.

Hospital outcomes

Table 3, footnote X^2 to be replaced with symbol ‘chi square' .

Table 3 to be cited after ‘ In critically ill patients …. P=0.045)

Clinical Presentation

For ‘Mean NEWS score was higher for patients admitted to the ICU (7.0 vs 5.9, p<0.01)’, median was reported in Table 1.

Table 4 & 5, small n to be used to indicate individual sample size. N for overall total.

Table 5, the description for superscript 2,3,4 in the footnote requires fine tuning.

Symbol colon : for the sub title to be omitted.

Some references were not conformed to the journal format.

Tables formatting to follow journal format.

Reviewer #4: Review for PLoS ONE

Aug 17, 2020

Title: Comorbidity and Clinical Factors Associated with COVID-19 Critical Illness and Mortality at a Large Public Hospital in New York City in the Early Phase of the Pandemic (March-April 2020)

This paper presents a study to describe patients admitted to NYC Health + Hospitals / Bellevue Hospital Center, in NYC, with COVID-19 in the month following the hospital’s first diagnosed case. Authors focused on comorbidities, clinical characteristics, and outcomes for patients admitted to ICU and non-ICU settings. However, there are questions that limit my enthusiasm of the paper, as outlined below.

1. Data Analysis:

a. Authors considered IQR, median, frequency, t-test and chi-squared tests, while they weren’t introduced at data analysis section. Please explain the descriptive statistics (for both continuous and categorical variables) along with the association tests that were applied across manuscript including t-test and chi-squared test. (Numbers 1 and 7 of caption of Table 1 need to be transferred to the data analysis with more details.)

b. Why authors considered parametric t-test compared with non-parametric methods? Is it based on known or unknown variance? Please justify this part since for the parametric t-test, the normality distribution needs to be assessed before applying t-test.

c. As an example, Table shows the association between race and requiring supplemental Oxygen. How authors consider the chi-squared test for such analysis with few observations or even zero values? Please adjust such analysis by applying an appropriate statistical analysis (such as Fisher’s exact test) and add to the data analysis section as well.

d. What is the statistical significant threshold for the statistical analyses across manuscript? Please add to the manuscript.

e. Statistically, the logistic regression model is fitted not estimated. But we can consider the logistic regression model to estimate the OR and/or RR. In addition, bivariate analyses or bivariable analyses? Please clarify this part at data analysis section.

2. Results:

a. For NEWS score, authors considered mean or median? Page 13, authors mentioned mean, so please be consistent across manuscript to report descriptive statistics.

b. Table 1, not easy to follow. For example for symptom duration or NEWS, it’s supposed to have (median, IQR), but what are those numbers after the IQR values? If they represent the total observations then please modify the table and re-do the Table in better way.

c. Table 1, for the CRP (admission lab test), please report all required values.

d. Please define “other” group in race as a caption or across the manuscript.

e. Why authors report cirrhosis (medical history), while it doesn’t show any observation/data?

f. Table 3: not easy to follow the association analysis for outcomes. Please add the P values (in the caption) to the Table and make it easier to follow. In addition, apply the previous comments regarding the chi-square test.

g. For the sum of the percentage of contingency table, it should be always 100%. So please modify the Table and exclude those two patients. In addition, the sum of the supplemental Oxygen, ICU is 135 not 136? Please modify Table 3 not easy to follow.

h. For the adjusted logistic model, how the authors decide which variables or covariates need to be included in the model to adjust the fitted model?

Reviewer #5: Thank you for the opportunity to review the well reported manuscript.

In general, the data analyses were appropriately performed and reported. Minor amendments with a recheck on percentage calculations throughout all tables were needed for a quality presentation. Detailed comments that focused mainly on the data analysis can be found from the attachment.

**********

6. 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

Reviewer #3: No

Reviewer #4: No

Reviewer #5: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Attachments

Attachment

Submitted filename: comments_08172020.docx

Attachment

Submitted filename: PONE-D-20-23829_reviewer comments.pdf

Comorbidity and Clinical Factors Associated with COVID-19 Critical Illness and Mortality at a Large Public Hospital in New York City in the Early Phase of the Pandemic (March-April 2020)

PONE-D-20-23829R1

Dear Dr. Filardo,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Wisit Cheungpasitporn, MD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I reviewed the revised manuscript and the response to reviewers' comments. Revised Manuscript is well written. All comments have been addressed and thus accepted for publication

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

Reviewer #4: All comments have been addressed

Reviewer #5: All comments have been addressed

**********

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: Partly

Reviewer #4: Yes

Reviewer #5: Yes

**********

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

Reviewer #2: I Don't Know

Reviewer #3: No

Reviewer #4: Yes

Reviewer #5: 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 #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: 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 #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: 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 #2: Thank you for your hard work and the thought given in the revision. Hopefully this will contribute to the wider body of research on Covid-19

Reviewer #3: The authors have put in great effort to address the comments

For Fisher's Exact Test, 1 or 2 tailed test to be stated.

Reviewer #4: All comments have been addressed. Thank you!

Minor comment, please make sure to use right name for Fisher's exact test across the manuscript (Please check caption Table 3). Please note that for enough sample, it is appropriate to consider the Chi-squared test. However for small sample size, the Fisher's exact test is the appropriate one.

Reviewer #5: All comments have been fully addressed and hence the manuscript has been accepted by me for publication.

**********

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: Rodney P Jones

Reviewer #3: No

Reviewer #4: No

Reviewer #5: No