Antibody response to SARS-CoV-2 infection in humans: A systematic review

Nathan Post; Danielle Eddy; Catherine Huntley; May C. I. van Schalkwyk; Madhumita Shrotri; David Leeman; Samuel Rigby; Sarah V. Williams; William H. Bermingham; Paul Kellam; John Maher; Adrian M. Shields; Gayatri Amirthalingam; Sharon J. Peacock; Sharif A. Ismail

doi:10.1371/journal.pone.0244126

Peer Review History

Original SubmissionSeptember 4, 2020
11 Nov 2020 Decision Letter - Nicholas J Mantis, Editor PONE-D-20-27927 Antibody response to SARS-CoV-2 infection in humans: a systematic review PLOS ONE Dear Dr. Ismail, 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. First, let me apologize for the delay in the review process. The two reviewers had widely differing opinions regarding the merit of the review article (reject; minor revision). My attempt to get a third reviewer was unsuccessful (at least in a timely manner). Personally, I lean more towards the minor revision status, but did not want to discount Reviewer 1's comments about the importance of updating the citations and avoid judging them on quality before they have undergone pre-peer review. Please update and adjust the review accordingly, provide a rebuttal letter and we can advance the manuscript upon re-submission. Please submit your revised manuscript by Dec 26 2020 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. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. 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Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [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: No 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? 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: In this outdated review, Ismail and colleagues provide a systematic review on antibody responses to SARS-CoV-2 infection in humans. Such an endeavour would be useful if up to date. It is odd to receive a review in October that covers manuscripts published no later than 26/06/2020, particularly when one of the areas that it aims to cover is antibody kinetics. A major problem of this work is how the authors grade studies quality. Are the authors experts in all what they have reviewed? If they are not, then they should refrain from attempting such evaluation. It is unclear whether the "adapted MetaQAT tool" robust enough to report on quality on all the subjects discussed in this review? Authors should refrain from grading the studies unless they are truly experts in the field and explain why they grade a study as low, medium or high. Several studies referenced by the authors have been updated since first publication in preprint, have been quite improved and are now published in top peer-reviewed journal. I was truly surprised to read that some peer-reviewed articles, published in top journals are graded as medium or low by the authors of this review. Do the authors, who cannot possibly be experts in all the areas covered in this review, believe that they know better than reviewers from these top journals? Yet, the authors indicate that “most studies were of moderate quality”… Table 2 is incomplete at best and clearly indicates that the authors have not read in detail the articles they reference. I started completing the table to indicate where the right reference should go but it is not the role of this reviewer to perform such task. This table should be completed once the authors read the references in detail (not only the abstracts). Some of the research questions raised by the reviewers are being answered with very good articles published lately and unfortunately not included in this review. While it is clear that as soon as someone starts to write a review on SARS-CoV-2 it becomes immediately outdated, the current review should include work at least until October. Reviewer #2: The manuscript submitted by Post et. al. is a systematic review of 150 serological studies on the humoral response to SARS-CoV-2 infection. The authors attempt to determine a consensus of the SARS-CoV-2 antibody response over time, the relationship of antibody responses to immune correlates, and the duration of humoral immunity. Importantly, the authors highlight the fact that discrepant results between serological studies are likely derived from the use of different assay platforms, antigens used, and patient cohort stratification. Their meta-analysis was able to predict preliminary kinetics for SARS-CoV-2 specific IgM, IgA, IgG, and neutralizing antibody. However, no consensus was obtained for immune correlates of the antibody response. Overall, the authors present a well-organized meta-analysis of the current serological studies on COVID-19, and I recommend this manuscript for publication with a minor edit as follows: 1. In Figure 3, please indicate which antigen/s were used for the kinetic prediction. If aggregate data was used from multiple antigens, be sure to clearly describe in the text and figure legend. ****** 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.0244126.r001
Revision 1
2 Dec 2020 Author Response Department of Primary Care and Public Health Imperial College London, UK FAO Nicholas J Mantis Academic Editor PLoS ONE 01 December 2020 Dear Professor Mantis Thank you for your email of 11/11/2020 providing reviewer comments on our manuscript “Antibody response to SARS-CoV-2 infection in humans: a systematic review”. We have now reviewed these and outline point-by-point responses below. Editorial comments 2. Thank you for stating the following in the Competing Interests section: "All authors have read the journal's policy and declare: no support from any organisation for the submitted work; JM is chief scientific officer, shareholder and scientific founder of Leucid Bio, a spinout company focused on development of cellular therapeutic agents; no other relationships or activities that could appear to have influenced the submitted work." Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: "This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared. Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf. RESPONSE: Thank you – we have now included a statement as outlined above in lines 635-6 in the manuscript. 3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. RESPONSE: We have now addressed this. The ethical approval statement has been moved to the methods section only, in lines 186-88. 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. RESPONSE: We have now addressed this. Reviewer #1 COMMENT: In this outdated review, Ismail and colleagues provide a systematic review on antibody responses to SARS-CoV-2 infection in humans. Such an endeavour would be useful if up to date. It is odd to receive a review in October that covers manuscripts published no later than 26/06/2020, particularly when one of the areas that it aims to cover is antibody kinetics. Some of the research questions raised by the reviewers are being answered with very good articles published lately and unfortunately not included in this review. While it is clear that as soon as someone starts to write a review on SARS-CoV-2 it becomes immediately outdated, the current review should include work at least until October. RESPONSE: Thank you for this comment. As the reviewer notes above, in the very fast-moving world of SARS-CoV-2 research at this time it is impossible to produce a manuscript that is fully up to date at any given time point. In addition, the comprehensive nature of the approach to article screening, selection, quality appraisal, data extraction and synthesis in systematic reviews means that the process of collating data after searches are performed is time consuming – the rigour of the approach is the primary means of reducing bias in a systematic review. We submitted this manuscript to PLoS ONE at the beginning of September 2020 – i.e. just over 2 months after the searches were completed – an unusually short time after the searches were completed by comparison with a majority of systematic reviews in the published literature. The Cochrane Collaboration suggests an average timeline of 12 months for systematic reviews from inception to submission; this review was completed in around 4 months, reflecting the context in which the work was undertaken and our goal of synthesising rapidly emerging evidence produced in response to a global pandemic. We do recognise the reviewer’s concerns around how up-to-date the manuscript is, and for this reason have added material in the discussion to reference more recently published literature (see the “Summary of Findings” section) up to 22/11/2020 drawing on expert input from members of the review team, and also relevant material captured in the Public Health England (PHE) COVID-19 literature digest, an evidence tracking tool produced by the PHE Knowledge and Library Services, and which is publicly available at: https://phelibrary.koha-ptfs.co.uk/coronavirusinformation/#DailyEvidenceDigest. However, we were unable because of capacity constraints to run searches in full to cover the period between 26/06/2020 and the present – and would have faced similar issues over the timeliness of the data if we had done so, given the need to screen, select, critically appraise and data extract from these sources. COMMENT: A major problem of this work is how the authors grade studies quality. Are the authors experts in all what they have reviewed? If they are not, then they should refrain from attempting such evaluation. It is unclear whether the "adapted MetaQAT tool" robust enough to report on quality on all the subjects discussed in this review? Authors should refrain from grading the studies unless they are truly experts in the field and explain why they grade a study as low, medium or high. Several studies referenced by the authors have been updated since first publication in preprint, have been quite improved and are now published in top peer-reviewed journal. I was truly surprised to read that some peer-reviewed articles, published in top journals are graded as medium or low by the authors of this review. Do the authors, who cannot possibly be experts in all the areas covered in this review, believe that they know better than reviewers from these top journals? Yet, the authors indicate that “most studies were of moderate quality”… RESPONSE: Thank you for this comment. Systematic review teams typically comprise a mixture of subject area specialists and those with expertise in review methodologies – it is highly unusual, and indeed usually impossible, for systematic review teams’ expertise to span all subject areas covered by reviews which tend by their nature to be broad. Our review team similarly comprises immunologists, microbiologists, epidemiologists, public health specialists and those with methodological expertise in systematic reviews. This mixed team structure was important in view of the multi-faceted nature of the review and need to consider basic science, clinical, public health and policy implications of the research reviewed. In addition, the structured approach to the review – clarity on search protocols, documented procedures for screening and selection of studies, data extraction from them and quality appraisal – is specifically designed to reduce bias. We were careful in this review to openly state our review approach and methodological, registering it on PROSPERO and reporting the review in accordance with PRISMA requirements. These steps are all recognised measures in the context of systematic reviews for reducing bias. As regards critical appraisal specifically, we chose the MetaQAT tool because it is an internationally-recognised critical appraisal tool (CAT) that has been validated including for use by non-subject area specialists. The tool focuses on broad aspects of study design and implementation. We made two minor modifications to this tool – to capture the publication type (peer-reviewed paper or pre-print) and to gather information on the assay or laboratory technique used (an area of particular relevance to the subject matter) – assessed by reference to material reported in the paper. This validated MetaQAT tool was the basis on which critical appraisals were made. In light of the concerns raised regarding quality appraisal, we have removed the follow-on step that we introduced when synthesising MetaQAT results for the paper: the use of a traffic-light style, low/medium/high quality categorisation (see changes tracked throughout the paper). We have instead retained our narrative comments on study quality (in both the main body of the paper and the supplementary materials). Our overall judgement remains, however, that a majority of the studies included in the review had significant methodological shortcomings that limit the aggregate conclusions that can be made from the published evidence. Finally, in regard to the question of preprint and peer-reviewed versions of the same studies; we included the most recent version of the relevant study that had been published within the time-frame of our searches. For reasons of rigour in the systematic review process, it was necessary to adhere to the time limits imposed by the searches and not cite later versions of specific papers published after the searches were completed as the content and even results presented may have changed post peer review. COMMENT: Table 2 is incomplete at best and clearly indicates that the authors have not read in detail the articles they reference. I started completing the table to indicate where the right reference should go but it is not the role of this reviewer to perform such task. This table should be completed once the authors read the references in detail (not only the abstracts). RESPONSE: We thank the review for flagging concerns regarding table 2. We have revisited this table to verify that referencing was correct and made some modifications as outlined in tracked changes. We have not, however, been able to identify errors of fact in our assessment of the evidence presented in papers cited in this table. Reviewer #2 COMMENT: In Figure 3, please indicate which antigen/s were used for the kinetic prediction. If aggregate data was used from multiple antigens, be sure to clearly describe in the text and figure legend. RESPONSE: Thank you for this comment. Figure 3 is in fact a schematic – i.e. intended to illustrate in general terms the trend over time in specific antibodies (across multiple antigens). We have included text to clarify this in the legend for the figure. Reporting of antigen type was in general very variable across included studies. Figure 2 captures this for first appearance of individual antibodies in those few studies that reported it in detail. We hope these responses help in addressing the reviewers’ concerns. If you have any further queries please do not hesitate to contact us. Yours, Sharif Ismail ST4 Public Health Registrar Wellcome Trust Clinical Research Training Fellow On behalf of the study authors https://doi.org/10.1371/journal.pone.0244126.r002
4 Dec 2020 Decision Letter - Nicholas J Mantis, Editor Antibody response to SARS-CoV-2 infection in humans: a systematic review PONE-D-20-27927R1 Dear Dr. Ismail, 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, Nicholas J Mantis Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0244126.r003
Formally Accepted
23 Dec 2020 Acceptance Letter - Nicholas J Mantis, Editor PONE-D-20-27927R1 Antibody response to SARS-CoV-2 infection in humans: a systematic review Dear Dr. Ismail: 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. Nicholas J Mantis Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0244126.r004

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