High SARS-CoV-2 seroprevalence in Karaganda, Kazakhstan before the launch of COVID-19 vaccination

Irina Kadyrova; Sergey Yegorov; Baurzhan Negmetzhanov; Yevgeniya Kolesnikova; Svetlana Kolesnichenko; Ilya Korshukov; Lyudmila Akhmaltdinova; Dmitriy Vazenmiller; Yelena Stupina; Naylya Kabildina; Assem Ashimova; Aigul Raimbekova; Anar Turmukhambetova; Matthew S. Miller; Gonzalo Hortelano; Dmitriy Babenko

doi:10.1371/journal.pone.0272008

Peer Review History

Original SubmissionMay 15, 2022
17 Jun 2022 Decision Letter - Cecilia Acuti Martellucci, Editor PONE-D-22-14174High seroprevalence of SARS-CoV-2 antibodies in Karaganda, Kazakhstan before the launch of COVID-19 vaccination.PLOS ONE Dear Dr. Yegorov, 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. Carefully consider the comments of the reviewers, which provide important points for improvement, and also the following: - Briefly explain the purpose of the pre-pandemic group in the Methods as well; - Explain which tests were used for which variables (instead of 'as appropriate'); - Please kindly provide the reference number of the ethical clearance for the larger study within which this serologic survey was performed; - Results are given for 99 subjects in the Table and for 98 subjects in the Results, please either correct or explain this discrepancy; - It is not clear whether 55 (methods) or 35 (results) subjects were selected for the neutralization assay, and by which criterion; - Please only use percentages in the table, as the numbers can be inferred thanks to the total in the top row (you can write "Results are expressed as percentages unless specified otherwise" in the title of the table; consistently, specify that for continuous variables you are providing the mean (and SD?); finally, the tests used should be explained as a note, not within the title of the table. Please submit your revised manuscript by Jul 31 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. 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'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Cecilia Acuti Martellucci, M.D. Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. 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. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match. When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section. 3. Thank you for stating the following in the Acknowledgments Section of your manuscript: "The study was funded by the Ministry of Education and Science of the Republic of Kazakhstan (AP09259123) and, in part, by the Nazarbayev University grant #280720FD1902 to GH. SY was supported, in part, by a M.G. DeGroote Postdoctoral Fellowship." We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "The study was funded by the The study was funded by the Ministry of Education and Science of the Republic of Kazakhstan (AP09259123, https://www.gov.kz/memleket/entities/edu?lang=en) and, in part, by the Nazarbayev University (https://nu.edu.kz/) grant #280720FD1902 to GH. SY was supported, in part, by a M.G. DeGroote Postdoctoral Fellowship. (AP09259123) and, in part, by the Nazarbayev University grant #280720FD1902 to GH. SY was supported, in part, by a M.G. DeGroote Postdoctoral Fellowship. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. All authors had full access to all the data in the study and the lead authors (IK, SY, DB) had final responsibility for the decision to submit manuscript for publication." Please include your amended statements within your cover letter; we will change the online submission form on your behalf. [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: The paper is well written and is relevant to current situation. Coming from one of the “stans” myself I realize the level of underreporting for such data. This makes it easier for me to understand the situation and importance of this paper. However, I have several concerns: 1. The history and situation with under reporting in the region is not fully explained. 2. The cohort chosen cannot be generalized to the whole population - this is mentioned in the paper, but I think it would be good to provide more details about reasons for choosing this particular cohort (availability, connections, etc) 3. Last, but not least, I felt that there is something missing in conclusion. Specifically, lack of recommendation for further studies and possible actions. It was established that the prevalence of COVID-19 in the region is much higher than officially reported. What can be recommended to the government, how to improve reporting in general, how this underreporting is connected to uptake of vaccinations? If possible this information can be added to the paper to make it more convenient complete. Reviewer #2: Dear Authors! On acquainting with the presented paper, I found no significant remarks in the Methodology, Results presentation, and the Discussion section. The topic's relevance cannot be considered overestimated, although the tension of the Covid-19 pandemic has significantly decreased. Given the chance of the possible upcoming pandemics, the global scientific community strives to acquire a deeper understanding of all the details of the present pandemic process. In this relation, information from the countries with a comparatively low level of healthcare, such as Kazakhstan (LMICs out of the EU), appears to be particularly valuable. A study on Sputnik V preceded this work, and linked preprints from the MedRxiv Yale were placed into the References. In the methodology narration, the solution to use the manufacturers' cutoff values as being more suitable was relevant, thus indicating the quality of the work done. The dubious moment was the number of pre-pandemic samples (N 10), though it seems that this circumstance did not interfere with the validity of the results obtained. The only I would suggest is to change your title slightly by inserting the brackets to lessen the number of commas: "High seroprevalence of SARS-CoV-2 antibodies in Karaganda (Kazakhstan) before the launch of COVID-19 vaccination" I found this conclusion the most important: "...serologically assessed SARS-CoV-2 exposure in this cohort was 14-15-fold higher than the reported all-time national and regional COVID-19 prevalence; the unusually high SARS-CoV-2 seroprevalence exceeding the estimates for many other countries." These data allow understanding of the shortcomings and pitfalls in the preventive strategies against the pandemic held in Kazakhstan. For instance, the paper showed the extremely low effectiveness of the screening by currently applied means. Albeit all the screened samples were negative, 59.2% of them turned out to be positive for anti-S IgA. I highly appreciated the integrity in presenting your data. ****** 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.0272008.r001
Revision 1
28 Jun 2022 Author Response Reviewer #1: The paper is well written and is relevant to current situation. Coming from one of the “stans” myself I realize the level of underreporting for such data. This makes it easier for me to understand the situation and importance of this paper. However, I have several concerns: Authors' response: We are very appreciative of the reviewer’s positive view of our work and thank the reviewer for the insightful comments and questions. Please kindly find our point-by-point responses to the reviewer’s remarks below. 1. The history and situation with under reporting in the region is not fully explained. Authors' response: Thank you for raising this point. To address this comment, we have now added additional information to the Introduction to describe the situation with regard to COVID-19 under-reporting in Kazakhstan (p3, lines 15-23 and p4, lines 1-3). 2. The cohort chosen cannot be generalized to the whole population - this is mentioned in the paper, but I think it would be good to provide more details about reasons for choosing this particular cohort (availability, connections, etc) Authors' response: Thank you for this very valid comment. This cohort was chosen for the serologic studies owing to funding availability and perceived feasibility in the context of the readily available resources and active participant recruitment within the infrastructure of the larger clinical trial. We have now added this information to the Materials and Methods (p4, lines 15-18). 3. Last, but not least, I felt that there is something missing in conclusion. Specifically, lack of recommendation for further studies and possible actions. It was established that the prevalence of COVID-19 in the region is much higher than officially reported. What can be recommended to the government, how to improve reporting in general, how this underreporting is connected to uptake of vaccinations? If possible this information can be added to the paper to make it more convenient complete. Authors' response: Thank you for this suggestion! We have modififed the Discussion/Conclusions (p 12, lines 9-23) to include our recommendations with regard to improving case reporting and pandemic surveillance using serological screening and alternative approaches. Reviewer #2: Dear Authors! On acquainting with the presented paper, I found no significant remarks in the Methodology, Results presentation, and the Discussion section. The topic's relevance cannot be considered overestimated, although the tension of the Covid-19 pandemic has significantly decreased. Given the chance of the possible upcoming pandemics, the global scientific community strives to acquire a deeper understanding of all the details of the present pandemic process. In this relation, information from the countries with a comparatively low level of healthcare, such as Kazakhstan (LMICs out of the EU), appears to be particularly valuable. A study on Sputnik V preceded this work, and linked preprints from the MedRxiv Yale were placed into the References. In the methodology narration, the solution to use the manufacturers' cutoff values as being more suitable was relevant, thus indicating the quality of the work done. The dubious moment was the number of pre-pandemic samples (N 10), though it seems that this circumstance did not interfere with the validity of the results obtained. The only I would suggest is to change your title slightly by inserting the brackets to lessen the number of commas: "High seroprevalence of SARS-CoV-2 antibodies in Karaganda (Kazakhstan) before the launch of COVID-19 vaccination" I found this conclusion the most important: "...serologically assessed SARS-CoV-2 exposure in this cohort was 14-15-fold higher than the reported all-time national and regional COVID-19 prevalence; the unusually high SARS-CoV-2 seroprevalence exceeding the estimates for many other countries." These data allow understanding of the shortcomings and pitfalls in the preventive strategies against the pandemic held in Kazakhstan. For instance, the paper showed the extremely low effectiveness of the screening by currently applied means. Albeit all the screened samples were negative, 59.2% of them turned out to be positive for anti-S IgA. I highly appreciated the integrity in presenting your data. Authors' response: We thank the reviewer for a very thoughtful and positive review of our work! We agree with the reviewer that the original title of the manuscript appeared somewhat cumbersome, therefore we have adjusted it to: “High SARS-CoV-2 seroprevalence in Karaganda, Kazakhstan before the launch of COVID-19 vaccination.” We would be happy to replace the comma with brackets and ultimately leave this decision to the reviewers' discretion. Editorial Comments: - Briefly explain the purpose of the pre-pandemic group in the Methods as well; Authors' response: Done, please see p 5, lines 8-11. - Explain which tests were used for which variables (instead of 'as appropriate'); Authors' response: Done, please see p 7, lines 13-18. - Please kindly provide the reference number of the ethical clearance for the larger study within which this serologic survey was performed; Authors' response: Done, we have added this information to the "Ethics Statement" (p 7, lines 19-22). - Results are given for 99 subjects in the Table and for 98 subjects in the Results, please either correct or explain this discrepancy; Authors' response: We apologize for the the lack of clarity here. Two out of 100 participants were excluded from S-IgA testing due to insufficient sample volume. However, because one of these two participants tested S-IgG+, they were still included in the "Prior COVID-19" category" despite the missing S-IgA result. We have now made edits to both the Table (see Table 1 footnote) and the Results (p.8, lines 8-16) to clarify this aspect. - It is not clear whether 55 (methods) or 35 (results) subjects were selected for the neutralization assay, and by which criterion; Authors' response: We are sorry for the confusion here. The neutralization assays were performed on 55 samples (of which 35 were classified as Prior COVID based on the S-IgG and S-IgA ELISA), as stated in the Methods. We have now clarified this in the Results (p8, lines 7-19). - Please only use percentages in the table, as the numbers can be inferred thanks to the total in the top row (you can write "Results are expressed as percentages unless specified otherwise" in the title of the table; consistently, specify that for continuous variables you are providing the mean (and SD?); finally, the tests used should be explained as a note, not within the title of the table. Authors' response: Thank you for these suggestions. We have edited the Table as requested by the Editor and among other edits specified in the Table footnote the following: "Continuous and categorical variables are provided as median/interquartile ranges and percentages, respectively." Attachments Attachment Submitted filename: PONE_Kadyrova_Response to Reviewer Comments.pdf https://doi.org/10.1371/journal.pone.0272008.r002
12 Jul 2022 Decision Letter - Cecilia Acuti Martellucci, Editor High SARS-CoV-2 seroprevalence in Karaganda, Kazakhstan before the launch of COVID-19 vaccination. PONE-D-22-14174R1 Dear Dr. Yegorov, 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, Cecilia Acuti Martellucci, M.D. 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 Reviewer #2: 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 Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 Reviewer #2: 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 Reviewer #2: 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) Reviewer #2: That's quite an improvement, and I am satisfied with all corrections made. I also agree with your present title. ****** 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 Reviewer #2: No ******** https://doi.org/10.1371/journal.pone.0272008.r003
Formally Accepted
18 Jul 2022 Acceptance Letter - Cecilia Acuti Martellucci, Editor PONE-D-22-14174R1 High SARS-CoV-2 seroprevalence in Karaganda, Kazakhstan before the launch of COVID-19 vaccination. Dear Dr. Yegorov: 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. Cecilia Acuti Martellucci Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0272008.r004

Open letter on the publication of peer review reports

PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.

We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.

Learn more at ASAPbio .