Rhinovirus/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, Malaysia

Yoong Min Chong; Yoke Fun Chan; Mohamad Fadhil Hadi Jamaluddin; M. Shahnaz Hasan; Yong Kek Pang; Sasheela Ponnampalavanar; Sharifah Faridah Syed Omar; I-Ching Sam

doi:10.1371/journal.pone.0273697

Peer Review History

Original SubmissionMay 29, 2022
28 Jul 2022 Decision Letter - Ruslan Kalendar, Editor PONE-D-22-15536Rhinovirus/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, MalaysiaPLOS ONE Dear Dr. Sam, 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. Reviewers point out the limitations of your research (Reviewer #2). Therefore, I ask the authors to prepare proper responses to these comments and to make appropriate additions to the text of the manuscript. Please submit your revised manuscript by Sep 11 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. 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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 Reviewer #1: The aim of the study was to detect viral etiologies in adults admitted with SARI in Kuala Lumpur, Malaysia in the 2 years before COVID-19, using molecular assays and metagenomics analysis. Samples of 489 patients were evaluated by a commercial multiplex nucleic acid assay (Luminex assay). In 57.1% of the patients one or more pathogens were detected. Rhinovirus/enterovirus (RV/EV) was the most prevalent agent that detected in nearly half of the samples, followed by influenza virus. In 105 Luminex negative samples were evaluated by a viral metagenomic analysis. A positive result was detected in 2% samples. In addition, factors related to increased risk of critical disease were studied. RV/EV isolates were characterized by sequencing. This is a study providing information regarding viral pathogens causing SARI in pre-COVID-19 era in a single center. It also reports the value of further investigation with metagenomics analysis to detect the pathogen in primer assay negative samples. Although results are not unique, the manuscript is well written, methods are clearly described and laboratory results are combined with patients clinical details. Reviewer #2: This manuscript is an epidemiological study investigating the causative virus of adult severe respiratory infections in Malaysia. I don't think there are any particular problems in considering the methods and results of this research. However, this study is an epidemiological study in a very limited area of Malaysia and is not considered to reflect the whole of Malaysia or Asia. In addition, this study was performed before the COVID-19 pandemic, and if possible, it would be better to investigate what kind of changes have occurred since the COVID-19 pandemic. Therefore, I don’t think it will be cited by many people at this point. Or, its scientific value is not high. ****** 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: Yes: A Arzu Sayıner 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.0273697.r001
Revision 1
3 Aug 2022 Author Response We thank the editor and reviewers for their time and effort. As requested, we will first respond to the following prompts listed in the editor's email: "a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent." As our clinical dataset contains at least 3 indirect patient identifiers (as defined by the reference cited by PLoS, i.e. http://www.bmj.com/content/340/bmj.c181.long), that is place of treatment, sex, and age, and there are other potential identifiers such as clinical severity (ICU/death) and year of treatment, our hospital’s Medical Research Ethics Committee felt that there is enough information to potentially identify patients, and therefore this database should not be made publicly available. Requests for data can be made to: Chairman, Medical Research Ethics Committee, 2nd floor, Kompleks Pendidikan Sains Kejururawatan, University of Malaya Medical Centre, Kuala Lumpur 59100, Malaysia. Tel: +603 79493209 E-mail: ummc-mrec@ummc.edu.my "b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories." Not applicable. Reviewer #1: "The aim of the study was to detect viral etiologies in adults admitted with SARI in Kuala Lumpur, Malaysia in the 2 years before COVID-19, using molecular assays and metagenomics analysis. Samples of 489 patients were evaluated by a commercial multiplex nucleic acid assay (Luminex assay). In 57.1% of the patients one or more pathogens were detected. Rhinovirus/enterovirus (RV/EV) was the most prevalent agent that detected in nearly half of the samples, followed by influenza virus. In 105 Luminex negative samples were evaluated by a viral metagenomic analysis. A positive result was detected in 2% samples. In addition, factors related to increased risk of critical disease were studied. RV/EV isolates were characterized by sequencing. This is a study providing information regarding viral pathogens causing SARI in pre-COVID-19 era in a single center. It also reports the value of further investigation with metagenomics analysis to detect the pathogen in primer assay negative samples. Although results are not unique, the manuscript is well written, methods are clearly described and laboratory results are combined with patients clinical details." Thank you for your positive review. Reviewer #2: "This manuscript is an epidemiological study investigating the causative virus of adult severe respiratory infections in Malaysia. I don't think there are any particular problems in considering the methods and results of this research. However, this study is an epidemiological study in a very limited area of Malaysia and is not considered to reflect the whole of Malaysia or Asia." This is an important limitation which we have acknowledged in the discussion (p23, lines 371-373): “It involved a single hospital, and only 105/218 (48.2%) negative samples underwent viral metagenomics analysis. Broader and more extensive surveillance studies are needed for more nationally representative data.” "In addition, this study was performed before the COVID-19 pandemic, and if possible, it would be better to investigate what kind of changes have occurred since the COVID-19 pandemic." This is an important point, as other respiratory viruses have been widely shown to have drastically reduced during the pandemic. We have separately published a similar study carried out in the early months of the pandemic which supports this, and have cited this in the discussion of the limitations of our study (p23, lines 375-377): “This study was conducted before the COVID-19 pandemic, which was associated with declines in other respiratory viruses globally, including at our centre [41,42].” (Ref 41 is our study, and can be found at https://doi.org/10.1016/j.jcv.2021.105000) "Therefore, I don’t think it will be cited by many people at this point. Or, its scientific value is not high." While the data is not novel, we believe, as we have written in the discussion, that “it provides important baseline data of circulating respiratory viruses in a tropical country.” This data is certainly lacking in adults in Malaysia and due to the cost of multiplex PCR/NGS and competing demands on limited diagnostic resources, is unlikely to be widely collected apart from sporadic, well-funded research projects or private hospitals. Furthermore, it is evident that as COVID-19 numbers have relatively waned this year, there has been a resurgence of respiratory viruses which were much reduced during the pandemic, such as influenza, RSV and adenovirus. Therefore, the post-pandemic virus circulation patterns are more likely to resemble the pre-pandemic circulation of multiple viruses. This adds to the importance of our baseline data for 2017-2019. Attachments Attachment Submitted filename: Response to reviewers.pdf https://doi.org/10.1371/journal.pone.0273697.r002
15 Aug 2022 Decision Letter - Ruslan Kalendar, Editor Rhinovirus/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, Malaysia PONE-D-22-15536R1 Dear Dr. Sam, 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, Ruslan Kalendar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0273697.r003
Formally Accepted
25 Aug 2022 Acceptance Letter - Ruslan Kalendar, Editor PONE-D-22-15536R1 Rhinovirus/enterovirus was the most common respiratory virus detected in adults with severe acute respiratory infections pre-COVID-19 in Kuala Lumpur, Malaysia Dear Dr. Sam: 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 Professor Ruslan Kalendar Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0273697.r004

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