Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort study

Faisal Alasmari; Mahmoud Mukahal; Alaa Ashraf Alqurashi; Molla Huq; Fatima Alabdrabalnabi; Abdullah AlJurayyan; Shymaa Moshobab Alkahtani; Fatimah Salem Assari; Rahaf Bashaweeh; Rana Salam; Solaf Aldera; Ohud Mohammed Alkinani; Talal Almutairi; Kholoud AlEnizi; Imad Tleyjeh

doi:10.1371/journal.pone.0272818

Peer Review History

Original SubmissionDecember 20, 2021
1 Mar 2022 Decision Letter - Asep K. Supriatna, Editor PONE-D-21-40113Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort studyPLOS ONE Dear Dr. Alasmari, 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 Apr 07 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. 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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 2. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. 3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. 4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ 5. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author. - https://www.medrxiv.org/content/10.1101/2020.07.09.20150136v1 - https://pubmed.ncbi.nlm.nih.gov/33341124/ - https://discovery.ucl.ac.uk/id/eprint/10117965/2/Walker_The%20duration%2C%20dynamics%20and%20determinants%20of%20SARS-CoV-2%20antibody%20responses%20in%20individual%20healthcare%20workers_AAM.pdf We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work. We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough. Additional Editor Comments: Dear Authors, We have reached a decision regarding the submitted manuscripts. Please revise your manuscript by adhering to the comment of the reviewers (and also to accomodate the reviewers' suggestion) as attached. Best regards, Academic Editor [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: Partly Reviewer #2: Partly ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: No ****** 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: No 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: My appreciation goes for the article. Here are some points to note: 1.For writing techniques, please refer to the publisher formats and articles that have been published. For example: the abstract should also contain the methods, the essential results, and conclusions in one complete paragraph; the second paragraph in line 93-95 one paragraph consists only 1 sentence. 2.In the abstract: (i)Important results from statistical surveys, and results from multivariable logistic regression should be added. (ii)The main results of the demographic statistics (Table 1) that specifically consider three factors: IgG seropositive status, clinical, and epidemiological respectively, should also be included. 3.In the methods: (i)HCW should be associated with the location where they work. It must be mapped what are four hospitals in one city look like, such as the capacity, etc. (related with line 117) (ii)Statictics methods should be explain more clearly particularly in multivariate logistic regression. Note: Is the multivariable logistic regression same with the multivariate logistic regression? (iii)Alpha used is too large. It should be 0.01. 4. In the results: (i)Please show the multivariable (multiple) logistic regression model, follows by the estimate parameters, chi-square table, etc. The example of mathematical model is as follows: (ii)The descriptive statistics is more attractive and interesting if it is represented by figure/graph, for example: B: Proportion of SARAS-Cov-2 samples across cities and regencies in West Java, Indonesia. C: Distribution of SARS-CoV-2 sequenced samples across different cities and regencies in West Java Indonesia. D: Demography of samples. Source: Azzania, et al. (2021). Analysis of SARS-CoV-2 Genomes from West Java, Indonesia. Viruses (13), 2097. (iii)Comparisons should suffice in unrelenting sentences. (What is the comparison table for?) (iv)Demographics should be linked to where they live. (v)Add an analysis of the effects of gender on that demographic, i. e. the effect of these results (3 factors: IgG seropositive status, clinical, and epidemiological) on each sex. Reviewer #2: 1. The objective of the study should be clearly stated in the abstract. 2. Table 3 (line 186): All the p-values are for the test of significance of the variables not for the regression coefficients. For e.g., there should be a p-value for "occupation", not for certain types of occupation (allied, resp. therapist) - consult your statistician. 3. Line 193: Fig 1. Trend in mean titer of IgG over the study period. A boxplot is not plotting a mean but a median (Q1, Q2=median, Q3). It would be informative if the titer of IgG are visualized as a line plot per individuals with time and provided by an average line plot for all titer of IgG. A lowess smoothing plot can be used for the average line plot. Since the individuals are a lot, a soft tone color (grey color, for example) for all individual plot is used. The color for smoothing plot should be bold and strong (black color, for example). An appropriate time scale should be used for the plot, if the date of the serologic tests were available, use "the time since the PCR test" or "the time since the first serologic test" (Choose the best available starting point). Consult your statistician to do such plot. 4. There is no sound Conclusion (Line 309). There is no answer (at least a comment) to how occupation affect seropositive outcomes (the risk factors), for example. How long the duration of detectable IgG, and how it is as compare to other countries. 5. Table 1 (Line 163), Characteristics n: there were 5 subjects (2528-273-22650=5) unclassified (seropositive or seronegative). This should be reported either in the table or in the text. 6. Be consistent with using or not using a thousand separator (,), for e.g. in line 118: "... a total of 7737 HCWs: 1,021 medical staff. ****** 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. Attachments Attachment Submitted filename: Review Manuscript PLOS USP (2).docx https://doi.org/10.1371/journal.pone.0272818.r001
Revision 1
15 Apr 2022 Author Response Academic editor Response 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. 1. DONE In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. 4. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager. Please see the following video for instructions on linking an ORCID iD to your Editorial Manager account: https://www.youtube.com/watch?v=_xcclfuvtxQ 4. DONE 5. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author. - https://www.medrxiv.org/content/10.1101/2020.07.09.20150136v1- https://pubmed.ncbi.nlm.nih.gov/33341124/https://discovery.ucl.ac.uk/id/eprint/10117965/2/Walker_The%20duration%2C%20dynamics%20and%20determinants%20of%20SARS-CoV-2%20antibody%20responses%20in%20individual%20healthcare%20workers_AAM.pdf We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work. We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough. 5. DONE Reviewer #1 My appreciation goes for the article. Here are some points to note: 1.For writing techniques, please refer to the publisher formats and articles that have been published. For example: the abstract should also contain the methods, the essential results, and conclusions in one complete paragraph; the second paragraph in line 93-95 one paragraph consists only 1 sentence. 1. DONE 2.In the abstract: (i)Important results from statistical surveys, and results from multivariable logistic regression should be added. (ii)The main results of the demographic statistics (Table 1) that specifically consider three factors: IgG seropositive status, clinical, and epidemiological respectively, should also be included. 2. (i) DONE (ii) DONE 3.In the methods: (i)HCW should be associated with the location where they work. It must be mapped what are four hospitals in one city look like, such as the capacity, etc. (related with line 117) 3. (i)Thank you for your comments, this information is not available. Line 117 has been modified (ii)Statistics methods should be explain more clearly particularly in multivariate logistic regression. Note: Is the multivariable logistic regression same with the multivariate logistic regression? (iii)Alpha used is too large. It should be 0.01. (ii)We did NOT use multivariate logistic regression, we used multivariable/multiple logistic regression. Logistic regression formula. (iii)We applied the standard practice of using alpha 0.05. 4. In the results: (i)Please show the multivariable (multiple) logistic regression model, follows by the estimate parameters, chi-square table, etc. The example of mathematical model is as follows: (ii)The descriptive statistics is more attractive and interesting if it is represented by figure/graph, for example: B: Proportion of SARAS-Cov-2 samples across cities and regencies in West Java, Indonesia. C: Distribution of SARS-CoV-2 sequenced samples across different cities and regencies in West Java Indonesia. D: Demography of samples. Source: Azzania, et al. (2021). Analysis of SARS-CoV-2 Genomes from West Java, Indonesia. Viruses (13), 2097. (i) Below is the model used in the study and we did not see the need to add it in the manuscript. Univariate logistic regression: The probability function is as below: p=ⅇ^(β_0+β_1 x)/(1+ⅇ^(β_0+β_1 x) ) Multivariable or Multiple logistic regression: The probability function for multiple explanatory variables is as below: p=ⅇ^(β_0+β_1 x_1+β_2 x_2+β_3 x_3+⋯.β_n x_n )/(1+e^(β_0+β_1 x_1+β_2 x_2+β_3 x_3+⋯.β_n x_n ) ) (ii) DONE, we added figures of descriptive statistics. (iii)Comparisons should suffice in unrelenting sentences. (What is the comparison table for?) (iv)Demographics should be linked to where they live. (iii) Thanks for this important comment, the written sentences are enough and the data in the table are more elaborative. (iv) Thank you for your comment. We don't have location data in our dataset. (v)Add an analysis of the effects of gender on that demographic, i. e. the effect of these results (3 factors: IgG seropositive status, clinical, and epidemiological) on each sex. (v) Table added Reviewer #2: 1.The objective of the study should be clearly stated in the abstract. 1. The objective has been added. 2. Table 3 (line 186): All the p-values are for the test of significance of the variables not for the regression coefficients. For e.g., there should be a p-value for "occupation", not for certain types of occupation (allied, resp. therapist) - consult your statistician. 2. We have used occupation in a cross tabulation (chi-square test) in Table 1 but in univariable regression analysis we used dummy variables for each occupational type. Hence, they are statistically sound. 3. Line 193: Fig 1. Trend in mean titer of IgG over the study period. A boxplot is not plotting a mean but a median (Q1, Q2=median, Q3). It would be informative if the titer of IgG are visualized as a line plot per individuals with time and provided by an average line plot for all titer of IgG. A lowess smoothing plot can be used for the average line plot. Since the individuals are a lot, a soft tone color (grey color, for example) for all individual plot is used. The color for smoothing plot should be bold and strong (black color, for example). An appropriate time scale should be used for the plot, if the date of the serologic tests were available, use "the time since the PCR test" or "the time since the first serologic test" (Choose the best available starting point). Consult your statistician to do such plot. 3. DONE (Figures added) 4. There is no sound Conclusion (Line 309). There is no answer (at least a comment) to how occupation affect seropositive outcomes (the risk factors), for example. How long the duration of detectable IgG, and how it is as compare to other countries. 4. Conclusion has been modified and table 6 in discussion demonstrated the differences among countries. 5. Table 1 (Line 163), Characteristics n: there were 5 subjects (2528-273-22650=5) unclassified (seropositive or seronegative). This should be reported either in the table or in the text. 5. DONE. Stated in the manuscript in abstract and result 6. Be consistent with using or not using a thousand separator (,), for e.g. in line 118: "... a total of 7737 HCWs: 1,021 medical staff. 6. DONE Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0272818.r002
12 Jun 2022 Decision Letter - Asep K. Supriatna, Editor PONE-D-21-40113R1Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort studyPLOS ONE Dear Dr. Alasmari, 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 27 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, Asep K. Supriatna, Ph.D Academic Editor PLOS ONE Additional Editor Comments: Dear authors, Thank you for submiting the revised version of the manuscript. The revised manuscript has been evaluated by the reviewer and there are still some issues need to be addressed. Please make correction based on the comment of the reviewer. Best regards, [Note: HTML markup is below. Please do not edit.] 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 #2: (No Response) ******** 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 #2: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: No ****** 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 #2: No ****** 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 #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 #2: Table 4 is still wrong (previously it was Table 3). All the p-values should be significance test for the variables notfor the regression coefficients. For e.g., there should be a p-value for 'occupation., not for certain types of occupation ('allied', 'resp. therapist', etc.). The p-value is the simultaneous test for the all dummy variables created by 'occupation' variable. Using this p-value you can evaluate the significance of occupation to the outcome (similar to that of the chi-square test but it is now adjusted for other variables). This is a typical mistake in using regression with dummy variables (with more than 2 categories). Do the same way for all variables with more than 2 categories ('previous medicine', 'medical condition', ... why not include the 'blood group' ...as in the chi-square test?). A sound conclusion then can be made from these p-values: what is the effect of "occupation", what is the effect of "previous medicine", etc. I suggest you also performing variable selection (model building). In a software like R, there is available procedure like dropterm() to calculate the simultaneous test, stepAIC() for variable selection. It should be available also in STATA, perhaps the TEST syntax. Fig 2.C The horizzontal axis should be the time, and the vertical axis is the IgG results. If the date of the test available, it would be informative if the time is "the time since the first serologic test" (not just Test 1, Test 2, Test 3). The attached figure is an example of such a plot. The individual plots are for all 185 (?) participants. The number of days since the first test may not be the same for all participants, even if the measurement time is planned every 3 months, therefore the horizontal axis is not just Test 1, Test 2, Test 3. (in the example, I made day 0 is the baseline and the Test 1 is participants who are underwent the next test (In your data, the baseline is the Test 1). Fig 2.B and a plot as suggested in the attached file are informative enough. ****** 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 #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.0272818.r003
Revision 2
17 Jun 2022 Author Response To: Asep K. Supriatna, Ph.D Academic Editor PLOS ONE Re: PONE-D-21-40113R1 Title: Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort study We would like to thank the Editorial Office and the reviewers for their time and valuable comments. We appreciate your efforts in critically reviewing our manuscript and we believe these suggestions would add more depth to our manuscript. We hope we have addressed your concerns appropriately. We look forward to seeing our manuscript published in PLOS ONE. Please find our response to your queries below: Academic Editor 4. Have the authors made all data underlying the findings in their manuscript fully available? Yes. Submitted in the link Reviewer #2: 1. Table 4 is still wrong (previously it was Table 3). All the p-values should be significance test for the variables not for the regression coefficients. For e.g., there should be a p-value for 'occupation., not for certain types of occupation ('allied', 'resp. therapist', etc.). The p-value is the simultaneous test for the all dummy variables created by 'occupation' variable. Using this p-value you can evaluate the significance of occupation to the outcome (similar to that of the chi-square test but it is now adjusted for other variables). This is a typical mistake in using regression with dummy variables (with more than 2 categories). Do the same way for all variables with more than 2 categories ('previous medicine', 'medical condition', ... why not include the 'blood group' ...as in the chi-square test?). A sound conclusion then can be made from these p-values: what is the effect of "occupation", what is the effect of "previous medicine", etc. I suggest you also performing variable selection (model building). In a software like R, there is available procedure like dropterm() to calculate the simultaneous test, stepAIC() for variable selection. It should be available also in STATA, perhaps the TEST syntax. 1. Thanks for your comment. We have assessed the association between occupation as a whole and serology test (outcome) in Table 1 using chi-square test and found it had a trend to significance (p = 0.08). That's why we tried to test using logistic regression to pinpoint whether any particular occupation is related to serology positivity compared to others. Unfortunately, in logistic regression we can't treat occupation as one single variable/category as it has 8 categories. If we do then Stata will treat it as a continuous variable. Hence, we must declare that it's a categorical variable and must declare which category will be the reference category (usually the category which holds most people (considered to be "normal"). That's why in Stata, we declared occupation to be a categorical variable and declared "Nurse" to be the :reference category" as this category held the highest number of people (n = 1351 (53.0%)) of all participants. Hence, we got OR and p value for all the other occupations compared to Nurses. We have also done model building by taking only those variables from simple logistic regression (unadjusted) that had p values less than 0.3 (either significant or potential to become significant). That's why you will see only a few variables in the multiple logistic regression (adjusted) section. As per your suggestion, we have done model building with variable selection. Please see new table-4 in the manuscript. 2. Fig 2.C The horizontal axis should be the time, and the vertical axis is the IgG results. If the date of the test available, it would be informative if the time is "the time since the first serologic test" (not just Test 1, Test 2, Test 3). The attached figure is an example of such a plot. The individual plots are for all 185 (?) participants. The number of days since the first test may not be the same for all participants, even if the measurement time is planned every 3 months, therefore the horizontal axis is not just Test 1, Test 2, Test 3. (in the example, I made day 0 is the baseline and the Test 1 is participants who are underwent the next test (In your data, the baseline is the Test 1). Fig 2.B and a plot as suggested in the attached file are informative enough. We thank the reviewer for his valuable suggestion. We have created a new lowess smoothing graph (figure 2-B). Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0272818.r004
12 Jul 2022 Decision Letter - Asep K. Supriatna, Editor PONE-D-21-40113R2Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort studyPLOS ONE Dear Dr. Alasmari, 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 Aug 26 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, Asep K. Supriatna, Ph.D Academic Editor PLOS ONE Journal Requirements: 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. Additional Editor Comments: Dear Editors, Thank you for submitting the revised version of the manuscript. I have read the revised manuscript and also the comments from the reviewer. There still some issues that still need to be addressed by following the reviewer's comment before the manuscript is ready for publication. Best regards, Asep [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.0272818.r005
Revision 3
22 Jul 2022 Author Response To: Asep K. Supriatna, Ph.D Academic Editor PLOS ONE Re: PONE-D-21-40113R2 Title: Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort study We would like to thank all the editors and reviewers for the valuable comments. We hope we have addressed all the comments appropriately. We look forward to seeing our manuscript published in PLOS ONE. Please find our response to the journal requirement: Journal Requirement 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. 1. Thanks for your comment. We have revised the reference list and completed it according to the journal requirement. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0272818.r006
27 Jul 2022 Decision Letter - Asep K. Supriatna, Editor Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort study PONE-D-21-40113R3 Dear Dr. Alasmari, 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, Asep K. Supriatna, Ph.D Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0272818.r007
Formally Accepted
2 Aug 2022 Acceptance Letter - Asep K. Supriatna, Editor PONE-D-21-40113R3 Seroprevalence and longevity of SARS-CoV-2 nucleocapsid antigen-IgG among health care workers in a large COVID-19 public hospital in Saudi Arabia: A prospective cohort study Dear Dr. Alasmari: 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. Asep K. Supriatna Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0272818.r008

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