Peer Review History
| Original SubmissionFebruary 5, 2021 |
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Dear Dr Brilot, Thank you for submitting your manuscript entitled "SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants" for consideration by PLOS Medicine. Your manuscript has now been evaluated by the PLOS Medicine editorial staff as well as by an academic editor with relevant expertise and I am writing to let you know that we would like to send your submission out for external peer review. However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire. Please re-submit your manuscript within two working days, i.e. by . Login to Editorial Manager here: https://www.editorialmanager.com/pmedicine Once your full submission is complete, your paper will undergo a series of checks in preparation for peer review. Once your manuscript has passed all checks it will be sent out for review. Feel free to email us at plosmedicine@plos.org if you have any queries relating to your submission. Kind regards, Dr Raffaella Bosurgi Executive Editor PLOS Medicine |
| Revision 1 |
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Dear Dr. Brilot, Thank you very much for submitting your manuscript "SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants" (PMEDICINE-D-21-00606R1) for consideration at PLOS Medicine. Your paper was evaluated by the editorial team (editors present Raffaella Bosurgi, Richard Turner, Caitlin Moyer, Beryne Odeny). It was sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below: [LINK] In light of these reviews, I am afraid that we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. Obviously we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers. In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript. In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the 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. 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 us at PLOSMedicine@plos.org. We expect to receive your revised manuscript by Apr 12 2021 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns. ***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.*** We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests. Please use the following link to submit the revised manuscript: https://www.editorialmanager.com/pmedicine/ Your article can be found in the "Submissions Needing Revision" folder. To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it. We look forward to receiving your revised manuscript. Sincerely, Dr Raffaella Bosurgi, Executive Editor PLOS Medicine ----------------------------------------------------------- Requests from the editors: Comments from the reviewers: Reviewer #1: This article titles "SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants" benefits from a reasonably large cohort followed for up to seven months. It presents a thorough and rigorous set of analyses, applying technically appropriate statistical methods. The findings are highly topical and important, providing a valuable and timely platform for urgent further research. Reviewer #3: Reviewer José Alcamí In this article Tea et al. Gives a comprehensive and broad perspective on the evolution and role of humoral responses against SARS-CoV-2. To this aim they study two Autralian cohorts, an hospital-based cohort (ADAPT n=100 patients) and a cohort of plasma donors (LIFE, n=159). The article is interesting but some of the data have been already published by other authors, which limits the originality of the results. The study asses humoral responses with different techniques. Main results are the longevity of antibody responses, particularly IgM antibodies that were detectable later than in previous articles. A correlation between IgG levels and neutralization capacity is shown. A subgroup of patients displaying high, broad and persistent humoral responses were identified. These patients would be good donors of hyperimmune plasma and besides high IgG levels they display also IgM antibodies which is an interesting observation. However, neutralization against emerging variants were significantly reduced in a proportion of patients. It this context it is interesting the decreased neutralization against 614G variants from patients infected with the original Wuhan 614D strain, an observation that as far as I know has not been reported so clearly. Major comments: 1. The authors determine SARS-CoV-2 antibodies against surface viral proteins (S, M and E) using a flow-cytometry assay. As the authors propose that this test should be used for assessment of antibody responses at it enhances the sensitivity for detection of Spike antibodies (Discussion lines 353-356) in comparison with conventional ELISA tests (Table 2, Euroimmun test and Diasorin) standard controls should be incorporated to rule out false positive results in the flow cytometry assay. 2. From figure 1A and methods (lines 477-483) it is not clear if Membrane and/or Envelope proteins were expressed individually in different cell lines or in the same cell line. Please clarify. 3. Related with the last point, in figure 1D membrane IgG antibodies are quantified. Did the authors quantify anti-Envelope antibodies as part of polyantigenic breadth? (lines 155-167). 4. Emerging variants studies are interesting but their relevance is low taking into account the current circulating Variants of Concern. Minor comments: 1. First sample was obtained beyond two months after a positive PCR test. Thus, one limitation of the study is the assessment of early antibody responses anti-SARS-CoV-2 2. Relationship between higher immunoglobulin levels and age probably is due to more severe disease in elderly people. This point should be mentioned. 3. Articles that characterize the presence of memory B-lymphocytes targeting the Spike protein should be mentioned as a proof of long-lasting immune memory (Papers from Shane Crotty for example). In summary, the article describes in two cohorts of patients with different clinical severity the range and evolution of IgM and IgG antibodies against different SARS-CoV-2 proteins using several techniques that combine ELISA, flow-cytometry and neutralization testing. Results are consistent and both technical approaches and some data are relevant. My major criticism is the minor originality of some findings that have already been reported. To be published in Plos Medicine, to include the reactivity and neutralization capacity of the studied plasma against current variants of concern (B.1.1.7, B1.351 and B.1.1.248) would increase the interest of the article. Any attachments provided with reviews can be seen via the following link: [LINK]
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| Revision 2 |
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Dear Dr. Brilot, Thank you very much for re-submitting your manuscript "SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants" (PMEDICINE-D-21-00606R2) for review by PLOS Medicine. I have discussed the paper with my colleagues and the academic editor James Beeson I am pleased to say that provided the remaining editorial and AE's points and production issues are dealt with we are planning to accept the paper for publication in the journal. AE points: My main outstanding issue with the paper is the reporting of statistical significance. There are a few problems the authors need to address 1. There needs to be consistent citation of p values where they state a difference is significant. There are several places where they report significant differences, but no p value provided in the text, and often it is missing in the figure/legend. They also describe higher or lower antibodies in different contexts in the text of the paper without indicating whether the differences are significant 2. They need to either indicate the p value or significance (or NS) in the figures themselves, or include them in the figure legend. Since many of their figures are very small, adding p values to the figure legend would be better and clearer. 3. Many figures are lacking any indication of a p value, either in the figure, the legend, or in the manuscript text. My recommendation to make this more consistent and accessible to readers is for them to put p values for each figure in the legend. this needs to be done for all figure sub-parts. If the difference is not significant, they should state the exact p value 4. When comparing differences in antibodies between clinical groups, there is no mention if they adjusted for covariates, or how they did this. The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript: [LINK] ***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.*** In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract. We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns. We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it. To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols 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. Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org. If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org. We look forward to receiving the revised manuscript by May 12 2021 11:59PM. Sincerely, Dr Raffaella Bosurgi, Executive Editor PLOS Medicine ------------------------------------------------------------ Requests from Editors: Comments from Reviewers: Any attachments provided with reviews can be seen via the following link: [LINK] |
| Revision 3 |
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Dear Dr Brilot, On behalf of my colleagues and the Academic Editor, James Beeson, I am pleased to inform you that we have agreed to publish your manuscript "SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants" (PMEDICINE-D-21-00606R3) in PLOS Medicine. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. Please be aware that it may take several days for you to receive this email; during this time no action is required by you. Once you have received these formatting requests, please note that your manuscript will not be scheduled for publication until you have made the required changes. In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process. PRESS We frequently collaborate with press offices. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximise its impact. If the press office is planning to promote your findings, we would be grateful if they could coordinate with medicinepress@plos.org. If you have not yet opted out of the early version process, we ask that you notify us immediately of any press plans so that we may do so on your behalf. We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/. To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols Thank you again for submitting to PLOS Medicine. We look forward to publishing your paper. Sincerely, Dr Raffaella Bosurgi Executive Editor PLOS Medicine |
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