Association of viral kinetics, infection history, NS1 protein with plasma leakage among Indonesian dengue infected patients

Leonard Nainggolan; Beti Ernawati Dewi; Arif Hakiki; Antony Joseph Pranata; Tjahjani Mirawati Sudiro; Byron Martina; Eric van Gorp

doi:10.1371/journal.pone.0285087

Peer Review History

Original SubmissionNovember 7, 2021
18 May 2022 Decision Letter - Ulrike Gertrud Munderloh, Editor PONE-D-21-31549Association of Viral Kinetics, Infection History and Plasma Leakage among Indonesian Dengue Infected PatientsPLOS ONE Dear Dr. Nainggolan, 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. Your study and findings are very similar to others that have been published previously, and is therefore considered a replication. For this reason, you must provide a strong scientific rationale to justify your study, and discuss the existing literature in detail to clarify this. In addition, please address the comments from both reviewers. Please submit your revised manuscript by Jul 02 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, Ulrike Gertrud Munderloh, Ph.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. 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. [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: No ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes 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: No ****** 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: No ****** 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 the manuscript PONE-D-21-31549, entitled “Association of Viral Kinetics, Infection History and Plasma Leakage among Indonesian Dengue Infected Patients” authors describe a small prospective observational study including 48 cases of dengue. The manuscript brings relevant information, although not new, that viral load is correlated with severity (plasma leakage/DHF) specially in primary dengue. The manuscript could be suitable for publication once small modifications are done. -Page 4, line 107: Authors should better describe the methodology and modifications of Lanciotti’s two-step reverse transcriptase PCR used to determine serotype. Which primers were used? -Page 6: What is the asterisk in Table 1? -Replace the term copy/mL for copies/mL -Table 3 legend should briefly describe method used for serotyping and statistical analysis. -Authors should briefly describe the dengue grades classification based on the 1997 WHO classification and include number of participants of each subgroup. Tables should differentiate hemorrhagic manifestation withing the groups as well as DHF I and II. All DHF patients displayed plasma leakage signs were classified as DHF since day 1? Table 3 should also include DF, DHF-DSS classification. -Authors should standardize group names: at some parts of the manuscript groups are called “with plasma leakage” and “without plasma leakage” and in other parts of the text/figures groups are called “plasma leakage” and “no plasma leakage” or non-plasma leakage. Some sentences are misleading, see examples below: -Page 7, Lines 170-171 “Between patients with and without plasma leakage, the viral load was significantly different on day 4 (P=0.010) of fever.” Should be rewritten to be more specific: Suggestion: “When comparing patients under primary infection with versus without plasma leakage, the viral load was significantly higher on day 4 (P=0.010) of fever in the leakage group.” -Page 7, Lines 170-173: “In patients with secondary infection, the viral load levels of plasma leakage patients were also higher compared to patients without plasma leakage especially on day 1, 3, and 4. However, we did not find a significant difference of viral load in patients with secondary infection (Figure 2B).” Suggestion: “In patients with secondary infection, the viral load levels of plasma leakage patients were also higher compared to patients without plasma leakage especially on days 1, 3, and 4 although no significant differences were found (Figure 2B).” -Page 9, line 211. Authors mentioned one case of coinfection in the study, however it is not clear whether the co-infection case was included in the data since table 2 show 28 cases of no leak and 20 cases of leak. -Language must be revised throughout the text. Some sentences are broken and need to be rewritten. See example below: Page 10, Lines236-237: “While this may imply more rapid viral clearance in secondary infection, further investigation is still needed as a different marker compared to our study is used.” Reviewer #2: This study from Nainggolan et al evaluate the association of viral kinetics, infection History and plasma leakage among dengue patients in Indonesia. The manuscript in poorly written with poor description of the methods which makes it difficult to understand. The more specific comments in whole is mentioned here. The authors need to clarify why 1997 WHO criteria used for the classification of dengue infection? I gather that this small sample (48) of patients were collected in 2010 and submitted for evaluation more than 10 years later. I am unable to understand why this significant delay in submission and weather some of the tests were done in freezed samples. It also appears that almost all admissions were within two days of the onset of fever and the number of patients developed DHF seems to be unusually high (41.7%) ? I am puzzled with this finding especially in this younger population (mean age 24.9). Other laboratory parameters like AST and AST levels should have mentioned if available and unavailability of those primary data questions the suitability for further evaluation. The dengue antibody testing (IgM and IgG) needs more details. What test kits were used and how the evaluation was done. More in-depth analysis would be preferred in the results. There were many topographical errors which are too many to be listed. ****** 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_FT-final.docx https://doi.org/10.1371/journal.pone.0285087.r001
Revision 1
23 Nov 2022 Author Response Reviewer #1 In the manuscript PONE-D-21-31549, entitled “Association of Viral Kinetics, Infection History and Plasma Leakage among Indonesian Dengue Infected Patients” authors describe a small prospective observational study including 48 cases of dengue. The manuscript brings relevant information, although not new, that viral load is correlated with severity (plasma leakage/DHF) specially in primary dengue. The manuscript could be suitable for publication once small modifications are done. -Page 4, line 107: Authors should better describe the methodology and modifications of Lanciotti’s two-step reverse transcriptase PCR used to determine serotype. Which primers were used? Answer: Thank you for the question. A two-step RT-PCR with slight modification was conducted. We have put more detailed information concerning this in the materials and methods section. -Page 6: What is the asterisk in Table 1? Answer: Thank you for the question. We have inserted more explanation regarding symbols used below the tables. -Replace the term copy/mL for copies/mL Answer: Thank you for your input. We have changed the related terms. -Table 3 legend should briefly describe method used for serotyping and statistical analysis. Answer: Thank you for your input. We have inserted the method used for serotyping and analysis below the table. -Authors should briefly describe the dengue grades classification based on the 1997 WHO classification and include number of participants of each subgroup. Tables should differentiate hemorrhagic manifestation withing the groups as well as DHF I and II. All DHF patients displayed plasma leakage signs were classified as DHF since day 1? Table 3 should also include DF, DHF-DSS classification. Answer: Thank you for the suggestion. All patients displayed plasma leakage signs throughout the course of study were classified as DHF. -Authors should standardize group names: at some parts of the manuscript groups are called “with plasma leakage” and “without plasma leakage” and in other parts of the text/figures groups are called “plasma leakage” and “no plasma leakage” or non-plasma leakage. Answer: Thank you for your input. We have made some corrections regarding this. Some sentences are misleading, see examples below: -Page 7, Lines 170-171 “Between patients with and without plasma leakage, the viral load was significantly different on day 4 (P=0.010) of fever.” Should be rewritten to be more specific: Suggestion: “When comparing patients under primary infection with versus without plasma leakage, the viral load was significantly higher on day 4 (P=0.010) of fever in the leakage group.” Answer: Thank you for your suggestion. We have made some corrections regarding this. -Page 7, Lines 170-173: “In patients with secondary infection, the viral load levels of plasma leakage patients were also higher compared to patients without plasma leakage especially on day 1, 3, and 4. However, we did not find a significant difference of viral load in patients with secondary infection (Figure 2B).” Suggestion: “In patients with secondary infection, the viral load levels of plasma leakage patients were also higher compared to patients without plasma leakage especially on days 1, 3, and 4 although no significant differences were found (Figure 2B).” Answer: Thank you for your suggestion. We have made some corrections regarding this. -Page 9, line 211. Authors mentioned one case of coinfection in the study, however it is not clear whether the co-infection case was included in the data since table 2 show 28 cases of no leak and 20 cases of leak. Answer: Thank you for your question. The one case of coinfection was included in the data. -Language must be revised throughout the text. Some sentences are broken and need to be rewritten. See example below: Page 10, Lines236-237: “While this may imply more rapid viral clearance in secondary infection, further investigation is still needed as a different marker compared to our study is used.” Answer: Thank you for your input. We have revised the language used throughout the text. Reviewer #2 This study from Nainggolan et al evaluate the association of viral kinetics, infection History and plasma leakage among dengue patients in Indonesia. The manuscript in poorly written with poor description of the methods which makes it difficult to understand. The more specific comments in whole is mentioned here. The authors need to clarify why 1997 WHO criteria used for the classification of dengue infection? Answer: Thank you for your question. We understand that WHO had published newer criteria concerning dengue classification, however we used 1997 WHO criteria due to the detailed definition of plasma leakage provided in this specific criterion. I gather that this small sample (48) of patients were collected in 2010 and submitted for evaluation more than 10 years later. I am unable to understand why this significant delay in submission and weather some of the tests were done in freezed samples. Answer: Thank you for your concern. Tests were not done in freezed samples. Delay in submission was due to personal reasons andin the process of writing the manuscript. It also appears that almost all admissions were within two days of the onset of fever and the number of patients developed DHF seems to be unusually high (41.7%) ? I am puzzled with this finding especially in this younger population (mean age 24.9). Other laboratory parameters like AST and AST levels should have mentioned if available and unavailability of those primary data questions the suitability for further evaluation. Answer: Thank you for your concern. We have inserted the AST and ALT levels in the Table 1. The dengue antibody testing (IgM and IgG) needs more details. What test kits were used and how the evaluation was done. Answer: Thank you for the input. More detailed methods have been inserted in the material and methods section. More in-depth analysis would be preferred in the results. There were many topographical errors which are too many to be listed. Attachments Attachment Submitted filename: Rebuttal Letter PLOS One.docx https://doi.org/10.1371/journal.pone.0285087.r002
27 Feb 2023 Decision Letter - Ulrike Gertrud Munderloh, Editor PONE-D-21-31549R1Association of Viral Kinetics, Infection History, NS1 Protein with Plasma Leakage among Indonesian Dengue Infected PatientsPLOS ONE Dear Dr. Nainggolan, 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. The technical detail that you have added in your revision is satisfactory, however the writing needs further revision to resolve lack of clarity. Please be sure to have your manuscript edited by a native speaker of the English language who is a scientist. If necessary, you might employ a scientific editing service. Please submit your revised manuscript by Apr 13 2023 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, Ulrike Gertrud Munderloh, 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. [Note: HTML markup is below. Please do not edit.] [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.0285087.r003
Revision 2
13 Apr 2023 Author Response The technical detail that you have added in your revision is satisfactory, however the writing needs further revision to resolve lack of clarity. Please be sure to have your manuscript edited by a native speaker of the English language who is a scientist. If necessary, you might employ a scientific editing service. Answer: Respected reviewers and editors, thank you for your inputs. We have reviewed our manuscript to improve the writing and have requested a native speaker to review our manuscript. May you find it satisfactory for publication in your journal. 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. Answer: Thank you for the input. We have reviewed our reference list and made some corrections. We have not found any retracted references however some adjustments to the reference list were made as follows: • All DOI identifiers, database’s unique identifiers have been removed to comply to samples of standard journal article provided by International Committee of Medical Journal Editors (ICMJE) • Reference number 2: we have changed Asia WROFS-E to World Health Organization Attachments Attachment Submitted filename: Rebuttal Letter PLOS One 1304.docx https://doi.org/10.1371/journal.pone.0285087.r004
17 Apr 2023 Decision Letter - Ulrike Gertrud Munderloh, Editor Association of Viral Kinetics, Infection History, NS1 Protein with Plasma Leakage among Indonesian Dengue Infected Patients PONE-D-21-31549R2 Dear Dr. Nainggolan, 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, Ulrike Gertrud Munderloh, Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0285087.r005
Formally Accepted
24 Apr 2023 Acceptance Letter - Ulrike Gertrud Munderloh, Editor PONE-D-21-31549R2 Association of Viral Kinetics, Infection History, NS1 Protein with Plasma Leakage among Indonesian Dengue Infected Patients Dear Dr. Nainggolan: 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. Ulrike Gertrud Munderloh Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0285087.r006

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 .