End-stage kidney disease and COVID-19 in an urban safety-net hospital in Boston, Massachusetts

Mohamed Hassan Kamel; Hassan Mahmoud; Aileen Zhen; Jing Liu; Catherine G. Bielick; Anahita Mostaghim; Nina Lin; Vipul Chitalia; Titilayo Ilori; Sushrut S. Waikar; Ashish Upadhyay

doi:10.1371/journal.pone.0252679

Peer Review History

Original SubmissionMarch 22, 2021
15 Apr 2021 Decision Letter - Bhagwan Dass, Editor PONE-D-21-09457 End-stage kidney disease and COVID-19 in an urban safety-net hospital in Boston, Massachusetts PLOS ONE Dear Dr. Upadhyay, 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 May 30 2021 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. 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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 Thank you for providing the date(s) when patient medical information was initially recorded. Please also include the date(s) on which your research team accessed the databases/records to obtain the retrospective data used in your study. Please list the exclusion criteria used for selecting patients in your methods section. In your ethics statement in the Methods section and in the online submission form, please provide additional information about the data used in your retrospective study. Thank you for stating that "Data was analyzed anonymously and participant consent was not required." Please clarify whether all data were fully anonymized before you accessed them. 5. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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. [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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ****** 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 ****** 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 ****** 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: You are correct in pointing out the limitation of your study given the small sample size of the ESKD cohort. I would revise your conclusions and discussion. You data, Table 4, suggests that when you control for co-morbid conditions such as diabetes, hypertension and CHF, ESKD is not an independent risk factor for a poor outcome. In addition, in my experience, ESKD patients tend to have higher ferritin levels (as an inflammatory marker) in general so the higher levels on admission may be difficult to interpret though the greater rise in ferritin along with other inflammatory markers in the ESKD cohort with poorer outcomes makes sense. Reviewer #2: Smaller cohort likely responsible for not being able to show higher mortality in ESKD patients compared to non-ESKD patients with COVID19 as seen in similar studies with larger cohort, otherwise, good data collection. ****** 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: Yes:** Anthony M. Valeri, MD Reviewer #2: 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. 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Revision 1
7 May 2021 Author Response Response to the reviewers We want to thank the academic editor and reviewers for their careful consideration of our manuscript titled “End-stage kidney disease and COVID-19 in an urban safety-net hospital in Boston, Massachusetts” PONE-D-21-09457. We appreciate the constructive feedback for clarification and improvement. Please find our responses to the comments below: Responses to comments by the Academic Editor: 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 Response: We have reviewed the style requirements and have made necessary changes to the manuscript. 2. Thank you for providing the date(s) when patient medical information was initially recorded. Please also include the date(s) on which your research team accessed the databases/records to obtain the retrospective data used in your study. Response: Thank you for your comment. All activities associated with our project were approved by the Boston University Medical Campus Institutional Review Board with waiver of informed consent to access non-anonymized patient data. Patient medical records from Boston Medical Center were accessed from May to July 2020. The sentence at the end of the second paragraph of the methods section has been amended to include the above dates. 3. Please list the exclusion criteria used for selecting patients in your methods section. Response: Thank you for your comment. Our study included data on 759 adults with a confirmed diagnosis of COVID-19 admitted to Boston Medical Center from Mary 4, 2020 to April 30, 2020. We excluded children under the age of 18 and kidney transplant recipients not receiving chronic maintenance dialysis treatments. We have added a sentence in the second paragraph of the methods section to clarify our exclusion criteria. 4. In your ethics statement in the Methods section and in the online submission form, please provide additional information about the data used in your retrospective study. Thank you for stating that "Data was analyzed anonymously and participant consent was not required." Please clarify whether all data were fully anonymized before you accessed them. Response: After obtaining the waiver of informed consent from the Institutional Review Board, demographic and clinical information were extracted directly from the electronic health records us. Health records were not anonymized prior to our access. Relevant data were entered in the database that did not include patient’s name. Data was then subsequently anonymously analyzed. We added three sentences in the section on “Data collection” to clarify the above points. 5. 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. Response: We have reviewed our reference list. No retracted paper has been included as a reference and we have not changed the reference list. Responses to comments by Reviewer 1- Anthony M. Valeri MD: Reviewer #1: You are correct in pointing out the limitation of your study given the small sample size of the ESKD cohort. I would revise your conclusions and discussion. You data, Table 4, suggests that when you control for co-morbid conditions such as diabetes, hypertension and CHF, ESKD is not an independent risk factor for a poor outcome. In addition, in my experience, ESKD patients tend to have higher ferritin levels (as an inflammatory marker) in general so the higher levels on admission may be difficult to interpret though the greater rise in ferritin along with other inflammatory markers in the ESKD cohort with poorer outcomes makes sense. Response: We want to thank Dr. Valeri for his comments. To address the reviewer’s comments, we have made following changes to the manuscript: a. In the conclusion section of the abstract, we have changed the sentence “The odds ratio of death was higher in ESKD patients, and consistent with the reports from other cohorts.” to “The odds ratio point estimate for death was higher in ESKD patients, but the difference did not reach statistical significance.” b. In the first paragraph of the discussion and conclusions section, we have clarified that our observation of a higher mortality in ESKD patients, while comparable in magnitude to the earlier report from New York, did not reach statistical significance. c. We agree with the reviewer that it is difficult to solely interpret higher admission ferritin level in patients with ESKD. Therefore, we have changed the sentence in the 4th paragraph of the discussion and conclusions section from, “The high ferritin seen in ESKD patients may be related to the difference in immune response between ESKD and non-ESKD patients.” to “While some degree of ferritin elevation may be expected in patients with ESKD due to their higher inflammation at baseline, the 6-fold higher admission value and the higher magnitude of in-hospital rise in ferritin observed in patients with ESKD may be related to the difference in immune response between ESKD and non-ESKD patients.” Responses to comments by Reviewer 2: Reviewer #2: Smaller cohort likely responsible for not being able to show higher mortality in ESKD patients compared to non-ESKD patients with COVID19 as seen in similar studies with larger cohort, otherwise, good data collection. Response: We want to thank the reviewer for the comment. We have acknowledged the limitation of our small sample size for the mortality outcome. However, unlike other published cohorts that have only examined admission laboratory parameters, we have examined the changes in laboratory makers of disease severity and inflammation during hospital stay, allowing for more robust comparisons of disease activity for both ESKD and non-ESKD groups. In addition, the examination of the trajectory of laboratory makers also enabled us to provide hypothesis-generating insight into COVID-19 disease biology in ESKD patients. Attachments Attachment Submitted filename: Response to the reviewers.docx https://doi.org/10.1371/journal.pone.0252679.r002
20 May 2021 Decision Letter - Bhagwan Dass, Editor End-stage kidney disease and COVID-19 in an urban safety-net hospital in Boston, Massachusetts PONE-D-21-09457R1 Dear Dr. Upadhyay, 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, Bhagwan Dass, MD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0252679.r003
Formally Accepted
26 May 2021 Acceptance Letter - Bhagwan Dass, Editor PONE-D-21-09457R1 End-stage kidney disease and COVID-19 in an urban safety- net hospital in Boston, Massachusetts Dear Dr. Upadhyay: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Bhagwan Dass Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0252679.r004

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