The clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantation

Paula M. Peçanha-Pietrobom; Giuseppe Gianini Figueirêdo Leite; James Hunter; Paulo R. Abrão Ferreira; Marcelo N. Burattini; Nancy Bellei; Jaquelina Sonoe Ota-Arakaki; Reinaldo Salomao

doi:10.1371/journal.pone.0258987

Peer Review History

Original SubmissionMay 13, 2021
2 Aug 2021 Decision Letter - Chiara Lazzeri, Editor PONE-D-21-15896 Clinical course of COVID-19 patients – with and without kidney transplantation – admitted at the hospital with moderate disease is mirrored by hematologic routine laboratory tests and deeply influenced by transplant history PLOS ONE Dear Dr. Salomao, 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 Sep 16 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. 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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. 2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information. Additional Editor Comments (if provided): [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? 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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: No ****** 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 made a great effort to support their thesis. They have great credit for following their population prospectively. However, the blood chemistry parameters they consider are also the first to change over the course of any infection and inflammation. There is no doubt that these changes are part of the course of COVID disease, but their ability to predict outcome is rather weak, correlation with the specific pathology under consideration should be improved. I suggest to the authors to improve the study design, not limiting themselves only to describing but trying to correlate what was observed to the specific pathology in a stronger and more unambiguous way. I also suggest that we organize the discussion better to make it more linear and less confusing. Better to stick to the description of the results and their interpretation more concisely. Reviewer #2: Could benefit from minor sytlistic/language revision for clarity sake. The findings of persistent elevation in NLR correlating with mortality is not unsurprising and did not change management, but the data may still be valuable for risk profiling. ****** 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 [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". 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Revision 1
18 Sep 2021 Author Response We thank the referees’ comments, which are responded point by point below. 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: Partly Response: we have reviewed the manuscript and hope to have improved its quality and presentation. Reviewer #2: Yes 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: 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 4. Is the manuscript presented in an intelligible fashion and written in standard English? Reviewer #1: Yes Reviewer #2: No Response: we have reviewed the manuscript and hope to have improved its quality and presentation. 5. Review Comments to the Author Reviewer #1: The authors made a great effort to support their thesis. They have great credit for following their population prospectively. However, the blood chemistry parameters they consider are also the first to change over the course of any infection and inflammation. There is no doubt that these changes are part of the course of COVID disease, but their ability to predict outcome is rather weak, correlation with the specific pathology under consideration should be improved. I suggest to the authors to improve the study design, not limiting themselves only to describing but trying to correlate what was observed to the specific pathology in a stronger and more unambiguous way. I also suggest that we organize the discussion better to make it more linear and less confusing. Better to stick to the description of the results and their interpretation more concisely. Response: Thank you for your comments. We have completely revised the manuscript, focusing on the cohort description and the main results obtained. To make the message clearer, we modified the tables that were in the main text and those presented as supplementary. For some comparisons (as in supplementary table 1) we changed the statistical approach to compare between patients deteriorating to critical illness and those with clinical recovery, and among the first ones between those surviving and not surviving. Furthermore, we added a Principal Components Analysis (PCA) in order to identify the set of variables that most correlates with outcomes. Results are presented focusing on the routine hematologic changes and clinical outcomes; the issue of kidney transplant recipients (KTR) COVID-19 patients is presented more concisely. The discussion was reorganized, as suggested. It is more concise (original version – 2167 words; revised version – 1489 words) and focused on the results. The quality of figures is also improved. The file “text marked with tracks” highlight part of these changes. Part of the texts that were removed could not be marked. We hope to have improved the quality of the manuscript and attended your expectations. Reviewer #2: Could benefit from minor sytlistic/language revision for clarity sake. The findings of persistent elevation in NLR correlating with mortality is not unsurprising and did not change management, but the data may still be valuable for risk profiling. Response: We thank you for the comments. Please, see the above response to the reviewer 1. The text was reviewed, it is more focused, concise and, hopefully, also clear. We hope to have improved the quality of the manuscript and attended your expectations. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0258987.r002
11 Oct 2021 Decision Letter - Chiara Lazzeri, Editor The clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantation. PONE-D-21-15896R1 Dear Dr. Salomao, 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, Chiara Lazzeri Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0258987.r003
Formally Accepted
4 Nov 2021 Acceptance Letter - Chiara Lazzeri, Editor PONE-D-21-15896R1 The clinical course of hospitalized moderately ill COVID-19 patients is mirrored by routine hematologic tests and influenced by renal transplantation. Dear Dr. Salomao: 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. Chiara Lazzeri Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0258987.r004

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