Dysregulated plasma lipid mediator profiles in critically ill COVID-19 patients

Francesco Palmas; Jennifer Clarke; Romain A. Colas; Esteban A. Gomez; Aoife Keogh; Maria Boylan; Natalie McEvoy; Oliver J. McElvaney; Oisin McElvaney; Razi Alalqam; Noel G. McElvaney; Gerard F. Curley; Jesmond Dalli

doi:10.1371/journal.pone.0256226

Peer Review History

Original SubmissionMarch 17, 2021
8 Jun 2021 Decision Letter - Fulvio D'Acquisto, Editor PONE-D-21-08835 Dysregulated Plasma Lipid Mediator Profiles in Critically Ill COVID-19 Patients PLOS ONE Dear Dr. Dalli, 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 Jul 23 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 Additional Editor Comments: 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.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: 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? 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: This is a well-written and well-organized submission that describes a role for lipid mediators, particularly special proresolving mediators (SPMs) in the pathogenesis of SARS CoV2 infection, and the potential of using these mediators for prediction of disease outcome. The data are clear and well-presented and the conclusions of the study well-supported. The only aspect that could be improved is the description of the trial design itself in the methods. It would make the paper much clearer if the experimental design was described in some detail. Reviewer #2: This is an outstanding scientific research report from an internationally recognized group of investigators. They report on the levels of specialized pro-resolving and pro-inflammatory lipid mediators in two groups of subjects with Covid-19: critically ill (admitted to ICU) and severe disease (hospitalized but not in ICU) using state-of-the-art liquid chromatography mass spectrometry. They found that plasma concentrations of both pro-inflammatory and pro-resolving lipid mediators were lower in critically ill patients compared to those with severe disease. Levels were lowest in those who died. Their findings establish a link between plasma lipid mediators, disease severity and survival in Covid-19. The findings have important implications for etiology of severe versus critically ill patients with Covid-19 and treatment. I have only a few minor comments: line 260: "liked" should be "linked" line 284: "the" should be "they" line 285: Sentence starting with "while" is not a complete sentence line 307: macrophage should be pleural line 308: deleted "note" Table 2: I believe this is for critically ill rather than severe patients. Severe is noted in the header. line 566: 'ration' should be "ratio" Table S1: It appears that the header "moderate" should be "severe" and the heading severe should be critically ill. ****** 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". 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. https://doi.org/10.1371/journal.pone.0256226.r001
Revision 1
27 Jul 2021 Author Response Reviewer #1: This is a well-written and well-organized submission that describes a role for lipid mediators, particularly special proresolving mediators (SPMs) in the pathogenesis of SARS CoV2 infection, and the potential of using these mediators for prediction of disease outcome. The data are clear and well-presented and the conclusions of the study well-supported. The only aspect that could be improved is the description of the trial design itself in the methods. It would make the paper much clearer if the experimental design was described in some detail. We would like to thank the reviewer for their positive comments. We agree with your comments about the study design and a more comprehensive description of the study methods has now been added. We have also amended a numerical error in the WHO scores, which was noticed upon review. Reviewer #2: This is an outstanding scientific research report from an internationally recognized group of investigators. They report on the levels of specialized pro-resolving and pro-inflammatory lipid mediators in two groups of subjects with Covid-19: critically ill (admitted to ICU) and severe disease (hospitalized but not in ICU) using state-of-the-art liquid chromatography mass spectrometry. They found that plasma concentrations of both pro-inflammatory and pro-resolving lipid mediators were lower in critically ill patients compared to those with severe disease. Levels were lowest in those who died. Their findings establish a link between plasma lipid mediators, disease severity and survival in Covid-19. The findings have important implications for etiology of severe versus critically ill patients with Covid-19 and treatment. I have only a few minor comments: line 260: "liked" should be "linked" line 284: "the" should be "they" line 285: Sentence starting with "while" is not a complete sentence line 307: macrophage should be pleural line 308: deleted "note" Table 2: I believe this is for critically ill rather than severe patients. Severe is noted in the header. line 566: 'ration' should be "ratio" Table S1: It appears that the header "moderate" should be "severe" and the heading severe should be critically ill. We would like to thank the reviewer for their kind comments and the recognition of significance of our hard. Moreover, we would like to express our appreciation for the detailed feedback provided, which allowed us to polish the delivery of this manuscript. We corrected the typos highlighted in your comment. Attachments Attachment Submitted filename: Palmas, Clarke et al response to reviewer comments.docx https://doi.org/10.1371/journal.pone.0256226.r002
3 Aug 2021 Decision Letter - Fulvio D'Acquisto, Editor Dysregulated Plasma Lipid Mediator Profiles in Critically Ill COVID-19 Patients PONE-D-21-08835R1 Dear Dr. Dalli, 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, Fulvio D'Acquisto, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0256226.r003
Formally Accepted
19 Aug 2021 Acceptance Letter - Fulvio D'Acquisto, Editor PONE-D-21-08835R1 Dysregulated Plasma Lipid Mediator Profiles in Critically Ill COVID-19 Patients Dear Dr. Dalli: 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 Professor Fulvio D'Acquisto Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0256226.r004

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