Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials

Farah Yasmin; Hala Najeeb; Abdul Moeed; Wardah Hassan; Mahima Khatri; Muhammad Sohaib Asghar; Ahmed Kunwer Naveed; Waqas Ullah; Salim Surani

doi:10.1371/journal.pone.0266245

Peer Review History

Original SubmissionOctober 29, 2021
7 Dec 2021 Decision Letter - Tariq Jamal Siddiqi, Editor PONE-D-21-32538Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trialsPLOS ONE Dear Dr. Surani, 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 Jan 21 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. 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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: Surani et al. conducted a meta-analysis on, “Safety and efficacy of colchicine in COVID-19 patients”, in which they reported that colchicine treatment decreased CRP levels and COVID-19 severity, with dimer levels, all-cause mortality and mechanical ventilation remaining seemingly unaffected. In my opinion, this study can be improved by incorporating the following points: 1. The strengths of the study are not clear, and it should be highlighted more as to what this study adds to the medical literature and how they address the current gap 2. The limitations may be somewhat enhanced further by highlighting additional limitations that resulted in study heterogeneity or why subgroup analysis was not performed. 3. Overall the quality of discussion is commendable, but it needs to proofread for example the capitalization error in line 281. 4. It can enhance the quality of results further if the number of studies that were included for mechanical ventilation and all-cause mortality was mentioned at the beginning of the paragraph. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: [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.0266245.r001
Revision 1
3 Mar 2022 Author Response January 10th, 2022 Editor-in-Chief PLOS-One Dear Editor, We are pleased to submit our revised manuscript entitled ‘Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials’ for consideration for publication in PLOS-One. We appreciate the comments we received from the editors and reviewers, all of which have been addressed in this revised version of the paper. Please find below the editor’s and reviewer’s comments in bold and the author responses. We further ensure that the material has not and will not be offered elsewhere for possible publication, as it is under consideration. We hope that these changes will make the manuscript competitive for publication in the journal. Salim Surani, MD, MPH, MSHM, FACP, FCCP, FAASM Adjunct Clinical Professor of Medicine and Pharmacology, Texas A&M University, USA. Clinical Professor, University of Houston (Voluntary Email: salimsurani@gmail.com You state: The strengths of the study are not clear, and it should be highlighted more as to what this study adds to the medical literature and how they address the current gap. Response: Thank you so much for pointing this out. We have now edited the manuscript to include the following details: This study has several strengths. Firstly, it includes all gold-standard RCTs that largely prove the safety and efficacy of Colchicine as an anti-inflammatory medication for different inflammatory conditions, including COVID-19. We have also included the findings of recent large-scale RECOVERY trial that contributed to the estimates in our study, and concluded that Colchicine has no significant effect on all-cause mortality and mechanical ventilation. Hence, our study expands the findings of prior literature by including contemporary trials that were missed by previous meta-analyses. The pooled estimates of prior meta-analyses were largely driven by non-randomized observational data leading to conflicting findings, the conclusion of our meta-analysis (based on only RCTs) bring consensus on the utility of Colchicine in these patients. Other reason being all included studies had some concern for risk of bias in all previous meta-analyses. Secondly, our meta-analysis comprising of only RCTs includes a summary of 16,048 COVID-19 positive patients indicating higher statistical power in comparison to previous meta-analyses. Lastly, we have demonstrated a higher methodological quality of the included trials using the standard recommended ROB-2 approach, to ensure the quality of data for inclusion of studies in our meta-analysis model. Given this, we believe our large-scale meta-analysis could serve as a benchmark against which the findings of individual studies and future trials could be compared. You state: The limitations may be somewhat enhanced further by highlighting additional limitations that resulted in study heterogeneity or why subgroup analysis was not performed. Response: Thank you so much for pointing this out. We have now edited the manuscript to include the following details: Different dosage and the duration of the loading dose and overall length of therapy presents as a limitation of this study. Due to the low number of studies per outcome and limited available data, a sensitivity analysis was performed in place of subgroup analysis to assess high heterogeneity. You state: Overall the quality of discussion is commendable, but it needs to proofread for example the capitalization error in line 281. Response: Thank you for pointing this out. The manuscript has been proof-read and corrected for grammatical and spelling errors. You state: It can enhance the quality of results further if the number of studies that were included for mechanical ventilation and all-cause mortality was mentioned at the beginning of the paragraph. Response: Thank you so much for pointing this out. We have now edited the manuscript to include the following details: All-cause mortality was reported in all five studies included. And Of the four studies included in quantitative analysis, there was no statistically significant reduction in mechanical ventilation. Attachments Attachment Submitted filename: Rebuttal Letter.docx https://doi.org/10.1371/journal.pone.0266245.r002
17 Mar 2022 Decision Letter - Tariq Jamal Siddiqi, Editor Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials PONE-D-21-32538R1 Dear Dr. Surani, 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, Tariq Jamal Siddiqi 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 ******** 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 ****** 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 ****** 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: (No Response) ****** 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 https://doi.org/10.1371/journal.pone.0266245.r003
Formally Accepted
28 Mar 2022 Acceptance Letter - Tariq Jamal Siddiqi, Editor PONE-D-21-32538R1 Safety and efficacy of colchicine in COVID-19 patients: A systematic review and meta-analysis of randomized control trials Dear Dr. Surani: 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. Tariq Jamal Siddiqi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0266245.r004

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