PONE-D-21-33433Outcomes of COVID‐19 infection in patients with hematological malignancies​- A multicenter analysis from PakistanPLOS ONE

Dear Dr. Zaki,

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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Sinan Kardeş, M.D.

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: No

Reviewer #2: Partly

Reviewer #3: Partly

Reviewer #4: Partly

Reviewer #5: Partly

Reviewer #6: Partly

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

Reviewer #1: I Don't Know

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

Reviewer #5: No

Reviewer #6: 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: Yes

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

Reviewer #6: 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: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: Yes

Reviewer #5: Yes

Reviewer #6: No

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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 investigated the outcome of patients with hematological malignancies and Covid-19 infection in a multicenter retrospective cohort in Pakistan. I agree with the authors, that more research in the management of patients with severe immune-suppression and Covid-19 infection is urgently needed.

The collected data in this study are scarce and do not allow any new conclusion.

Unfortunately, this study does not provide any new insights in the field of Covid-19 infection in patients with hematological malignancies.

Reviewer #2: The current study describes 107 patients with COVID-19 and HM retrospectively collected from Pakistan (multicenter). I suggest the following changes to the manuscript:

- Needs extensive English editing.

- What is the rationale for not starting the inclusion criteria from the day of the epidemic start and choosing almost a year after this to start?

- Include the methodology (test details) of the COVID-19 diagnosis.

- The methodology section lacks important details (definitions [disease, variables, outcomes, severity classifications] and detail the statistical analysis.

- Add details of COVID-19 severity and severity classification.

- I suggest including a univariable and a multivariable analysis on the mortality and including important predictors in these analyses.

Reviewer #3: In the manuscript, PONE-D-21-33433, Zaki et al reported the COVID-19 infection outcomes of 107 patients with history of hematological malignancies that were presented at the Oncology Department of 5 tertiary care hospitals in Pakistan from February 2020 to August 2020. The authors summarized the overall clinical outcome, the patient characteristics, clinical presentations, treatments administered, and mortality rate stratified by age, type of malignancy and oncological treatment status for COVID19 in patients with hematological malignancy.

Specific concerns:

1. The authors concluded that their data supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection. However, there is no matched control cases in this study to compare with.

2. No statistical significance (P value) was assessed in the mortality rate analyses.

3. The calculation of mortality rate in Table 2 is wrong, which is the reason why the mortality rate in each group is lower than the overall mortality rate of the study cohort (28%). For example, when stratified for age, the authors said the mortality rate was 7.4%, 5.6% and 10.2% in the age groups 10-30 years, 31-50 years, and 51-70 years respectively. However, the true death rate should be 19.5% (8/41), 17.6 (6/34), and 37.9% (11/29), respectively.

4. Table 1 should be divided into multiple tables.

5. It might be better to present the data in Table 2 by one or more figures.

6. There are sporadic grammar errors throughout the manuscript.

Reviewer #4: Peer-review report

Title: “Outcomes of COVID‐19 infection in patients with hematological malignancies- A multicenter analysis from Pakistan”

Manuscript number: PONE-D-21-33433

Reviewer comment

- Thank you for inviting me to review this paper. I congratulate the authors for writing this research article. Based on their study, the authors describe the outcome of COVID-19 infection in patients with hematological malignancy. However, the document needs revision in the methodology and analysis section before considering the paper for publication.

Abstract

- Please expand the term COVID-19 and SARS-CoV-2

- In the method part, explain how the data is and analyzed and presented

- Replace …‘from February 2020 to August 2020’ with … from February to August 2020’.

- Please spell out numbers when they occur at the beginning of a sentence.

- The authors said that mortality rate is high in patients aged 50 and above without putting any statistical indicator (e.g. p-value). Accordingly, the information seems invalid.

- The conclusion of the study support the knowledge in the existing literature, but it seems relevant to add recommendation. //

Introduction

-explained fairly.

Method

Needs major revision considering the following points

- Clear description of the study setting, study populations, eligibility criteria (inclusion and exclusion criteria), data collection procedure, operational definition (if applicable), and ethical approval of the study (even a little is stated in the declaration section).

- In the statistical analysis part, why the authors preferred to use median over mean? Do the authors check the distribution of the data?

- Similarly, the chi-square test is performed. However, it is unclear where they put the report of this test in the result part.

- With the existing data on your hand, you can consider identifying the factor (s) associated with the COVID-19 outcome (optional).

Result

-Revise based on previous comment on the analysis part. You have to put the chi-square (optional) and the p-value in the stratification of mortality table.

Discussion

-Be consistent on the use of the word COVID-19. You have written as covid 19, COVID-19,...

-Expand the term ASH

- At the end of the discussion part please give a separate sub-heading and label as ‘conclusion’. In this part you can put your conclusion and recommendation (s).

- Revise the lists of abbreviation

Reviewer #5: In this study, Zaki et al, carried out a multicenter, retrospective, cohort study including 107 patients (aged ≥14 years) with diagnosis of hematological malignancy admitted to 5 tertiary care hospitals with laboratory-confirmed and symptomatic COVID-19.

As the authors rightly point out, the value of the study lies in being the first multicenter analysis from Pakistan and aimed at investigating outcome of patients with hematological malignancies and COVID-19 in a context with limited health care resources.

The outcomes in COVID- 19 cancer patients is a topic of great interest, and for this reason, a deeper characterization of the study population is recommended. In particular, the author should specify:

- the duration of follow-up

- the criteria used to define the severity of COVID-19 at admission

- patients with progressive disease, remission or in active therapy

Although in this study, the overall mortality mirrors data from studies carried out in other countries, suggesting a high risk for severe COVID-19 infection and mortality also in these patients, the author should discuss results comparing data with:

- mortality estimates for COVID-19 in the general population, possibly according to sex and stratified for age

- mortality estimates for pre-covid cohort with hematological malignancies, possibly stratified according to sex, age, type of hematological malignancy.

In order to make data analysis clearer to readers, characteristics of the study population should be reported in a table, with information on age/age groups, sex, comorbidities, type of hematological malignancy, disease status and therapy, COVID-19 severity, referred for all patients, survivors and non-survivors. And the results should be discussed accordingly. In particular, the features of the cohort study can be compared according to COVID-19 severity and outcome

Although the sample size makes this study not sufficiently robust to assess events and risk factors that can predict death in this clinical setting, a deeper statistical analysis evaluating association with overall survival of variable such as age, sex, comorbidity, type and status of neoplasia, etc., would help to objectively characterize these patients

Reviewer #6: The article captures data from the real world but has certain limitations, some of which have been highlighted. The comparative mortality and hospitalization statistics in the general population without hematological malignancies should be mentioned for the reader to make a fair comparison. The English should be brushed up. Have edited some of the errors in the attached pdf, but there are more.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes: Zhijun Duan

Reviewer #4: No

Reviewer #5: No

Reviewer #6: Yes: Prantar Chakrabarti

[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.]

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Attachments

Attachment

Submitted filename: PONE-D-21-33433_reviewer.pdf

PONE-D-21-33433R1Outcomes of COVID‐19 infection in patients with hematological malignancies​- A multicenter analysis from PakistanPLOS ONE

Dear Dr. Zaki,

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.

Please submit your revised manuscript by Apr 23 2022 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Sinan Kardeş, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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: (No Response)

Reviewer #3: All comments have been addressed

Reviewer #4: All comments have been addressed

Reviewer #5: 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 #3: Yes

Reviewer #4: Yes

Reviewer #5: Partly

**********

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

Reviewer #1: Yes

Reviewer #3: Yes

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 #1: 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 #1: No

Reviewer #3: No

Reviewer #4: No

Reviewer #5: No

**********

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 of the manuscript "Outcomes of COVID‐19 infection in patients with hematological malignancies​- A multicenter analysis from Pakistan“ have partially addressed previous comments. The manuscript still needs intensive language editing.

Reviewer #3: The authors have addressed most of the concerns from the 1st-round review, and this reviewer is satisfied with the improved quality of the revised manuscript. However, the English language skill still needs to be improved.

Reviewer #4: Dear /sir, most of the comments given were addressed correctly. I have a few suggestions to improve the readability of this manuscript before publication is commenced. My concerns are:-

- Please expand the term COVID-19 and SARS-CoV-2 at the beginning of the abstract page 3 line 3

- Replace …‘from February 2020 to August 2020’ with … from February to August 2020’ page 3 line 11.

- The information included in the operational definition must be cited with appropriate literature/s.

- Authors should check for typos and grammatical errors throughout the manuscript which need to be edited after careful reading.

Reviewer #5: I sugest the authors to keep the first 3 paragraph of Baseline characteristics, taking care to integrate the information added in the revised version to avoid repetitions

The comparative mortality and hospitalization statistics in the general population should be mentioned for the reader to

make a fair comparison.

English should be improved

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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 #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.

Outcomes of COVID‐19 infection in patients with hematological malignancies​- A multicenter analysis from Pakistan

PONE-D-21-33433R2

Dear Dr. Zaki,

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,

Sinan Kardeş, 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 #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 #3: Yes

Reviewer #4: Yes

Reviewer #5: Yes

**********

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

Reviewer #3: Yes

Reviewer #4: Yes

Reviewer #5: N/A

**********

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 #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 #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 #3: (No Response)

Reviewer #4: (No Response)

Reviewer #5: The authors of the manuscript "Outcomes of COVID‐19 infection in patients with hematological malignancies- A multicenter analysis from Pakistan“ have addressed previous comments.

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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 #3: No

Reviewer #4: No

Reviewer #5: No