PONE-D-21-06171

Simple Scoring Tool to Estimate Risk of Hospitalization and Mortality in Ambulatory and Emergency Department Patients with COVID-19

PLOS ONE

Dear Dr. Webb,

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.

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Carlo Torti

Academic Editor

PLOS ONE

Additional Editor Comments:

Unfortunately, your work lacks external validation and comparison with known and validated risk scores. For these reasons, it is not suitable for publication as it appears now.

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3. In the Methods section, please provide additional information regarding the methods used to systematically guide the scoring tool development.

4.  Thank you for stating the following in the Competing Interests section:

"IP reports salary support through a grant from the National Institutes of Health (U.S.A). SB reports salary support from the U.S. NIH, Centers for Disease Control and the Department of Defense; he also reports receiving support for chairing a data and safety monitoring board for a respiratory failure trial sponsored by Hamilton, effort paid to Intermountain for steering committee work for Faron Pharmaceuticals and Sedana Pharmaceuticals for ARDS work, support from Janssen for Influenza research, and royalties for books on religion and ethics from Oxford University Press/Brigham Young University. BW reports partial salary support from a U.S. Federal grant from AHRQ.  ES receives partial salary support through grants from the Centers for Disease Control.

At the time of submission, Intermountain Healthcare and the University of Utah have participated in COVID-19 trials sponsored by: Abbvie, Genentech, Gilead, Regeneron, Roche, and the U.S. National Institutes of Health ACTIV and PETAL clinical trials networks; several authors (BW, IP, JB, SB, ES) were site investigators on these trials but received no direct or indirect remuneration for their effort.  ES, BJW, SMB and MS are members of the Utah crisis standards of care scarce medication committee."

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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: No

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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: No

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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 propose a new model capable of stratifying the risk of hospitalization and mortality in patients with COVID-19 outpatient or who access the emergency department.

The strengths of the score are:

1) the sample size and, consequently, the number of the score validation population;

2) the simplicity of the score, as it uses anamnestic and non-laboratory data.

Nonetheless, several issues need to be addressed by the authors:

1) Like all scores, it requires external validation, as the data is drawn from what is observed. For example, a state's health system, whether public or private, certainly influences health care towards the weakest and poorest social classes. This data can have repercussions on the results of the score. It is no coincidence that belonging to a more impoverished community represents a risk factor (OR 1.8, CI95% 1.5-2.2, p-value <0.0001).

2) A second observation regards the category of immunosuppressed patients. First of all, this label includes a multitude of different patients (recipient of a solid organ or hematopoietic stem cell transplant, on chemotherapy, biologic or other immunosuppressive agents targeting B or T cell activity, chronic corticosteroids at a prednisone-equivalent dose of 20 mg per day or more significant for more than 30 days, human immunodeficiency virus complicated by acquired immunodeficiency syndrome (AIDS), heritable immunodeficiency). It is hard to think that an HIV patient is similar to an immunodeficient patient because transplanted. Also, because the data in the literature show that some immunosuppressive states could even be protective. Furthermore, terminal metastatic patients not eligible for treatment have been excluded, and, consequently, we have no data on this population, which also falls into the category of patients considered "fragile". Being 6 months old doesn't make COVID infection any less dramatic. So, I would suggest breaking the "immunosuppression" label into its components and analyzed individually.

3) Finally, I have an objection to the usefulness of introducing a new score without making a comparison with those already present. For example, it would be nice to compare the data obtained against a known and validated score like the Charlson comorbidity index, which is similar to that proposed.

Reviewer #2: Simple Scoring Tool to Estimate Risk of Hospitalization and Mortality in Ambulatory and Emergency Department Patients with COVID-19

Title: Appropriate.

Abstract: Appropriate and informative.

Key words: Short 5 keywords are need; Hospitalization, Scoring, Cohort.

Introduction: Appropriate and informative.

Aim of work: Appropriate and informative.

Methodology: Appropriate and informative. IRB Approval/ Number is needed.

Results: Calibration of the final multivariate logistic regression model (The Hosmer–Lemeshow test) is needed.

The Discrimination of the final multivariate logistic regression model should be assessed by the area under the receiver operator characteristic (ROC) curve.

Discussion: Appropriate, however I expected more comparisons with recent studies on the same topic.

References: Please use Vancouver’s Style in all references.

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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

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Simple Scoring Tool to Estimate Risk of Hospitalization and Mortality in Ambulatory and Emergency Department Patients with COVID-19

PONE-D-21-06171R1

Dear Dr. Webb,

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,

Carlo Torti

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

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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

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

Reviewer #1: 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

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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 #1: 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: The Authors have completely addressed my concerns. The manuscript is significantly improved respect to the initial version. I have not further questions.

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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