Clinical characteristics of 82 cases of death from COVID-19

Bicheng Zhang; Xiaoyang Zhou; Yanru Qiu; Yuxiao Song; Fan Feng; Jia Feng; Qibin Song; Qingzhu Jia; Jun Wang

doi:10.1371/journal.pone.0235458

Peer Review History

Original SubmissionMarch 20, 2020
9 Jun 2020 Decision Letter - Xia Jin, Editor PONE-D-20-07999 Clinical characteristics of 82 cases of death from COVID-19 PLOS ONE Dear Dr. wang, 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 respond to all comments made by the reviewer and make changes to your manuscript accordingly. Please submit your revised manuscript by Jul 24 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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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. We will update your Data Availability statement on your behalf to reflect the information you provide. 3. 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. 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Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: This article is timely given the present pandemic for COVID 19> It is a descriptive retrospective review of the epidemiological descriptions of over 80 deaths at a single hospital in Wuhan in the first month of the epidemic. as such it is an informative article. There are a few issues of note that need to be addressed: 1.) There is no definition of "severe Illness". Results section paragraph 2 line 4 77/82 were admitted with severe illness. 2,) Line 4 of paragraph 2 of Results. Incubation time is unclear how it can be calculated. The definition in method noted this calculation to be from time of contact of transmission exposure to date to symptoms. Only 2 patients reported exposure so is incubation time calculated for only those 2. If so, I don't find it very informative or helpful. 3.) Table 1 Comorbidity - first listing is "ALL" Does that mean ANY? Not clear what that means. 4.) Table 1 Comorbidity - please define disease of reduced immunity- is this Collagen vascular disease> is this HIV? what does this mean? 5.) Table 3 needs clarification and some editing....right now the list is just too long and difficult to find your way through--for example it notes Neutrophyl count ( is that a mean??) then lists % with very low and very high. This was the same for every value given. There must be an easier clearer way to present this data. 6.) Table 3 notes radiographic data in the table but it really lists only Bilateral infiltrates at 100% of patients. This would be easier to be removed form the table and listed at the time of the statement o "severe illness on presentation - is this in fact what you meant? 7.) Table 3 what is acquired infection? nosocomial infection during admission? 8.) The surprise is that only 17% of patients go to MICU --- this appears first in the table 3 and then later there is a brief mention of this in the discussion. This is important and needs to move up much sooner in your paper. 83% of deaths never received Critical Care Support due to the overwhelming of your system. Only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. This all speaks to the overwhelming of the system and needs to be highlighted. You might look to see if the patients who did make it into the MICu were any different than the ones who did not? 9.) What anti viral medications were given? Table 3 again. I think the paper is important glimpse into the early phase of the pandemic and is publishable with a bit of more work and editing. ****** 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: E Jane Carter [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.0235458.r001
Revision 1
15 Jun 2020 Author Response 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 Response: The style has been checked and modified. 2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: 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. 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. We will update your Data Availability statement on your behalf to reflect the information you provide. Response: There are no restrictions. The data set is uploaded as Supporting Information files (.xlsx). 3. 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 Response: ORCID: 0000-0003-3941-2507 for Dr. Wang has been validated in Editorial Manager and added to the manuscript. 4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Response: Captions and files for Supporting Information has been included and updated, in-text citations are matched. 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) Response to reviewers Reviewer #1: 1. This article is timely given the present pandemic for COVID 19> It is a descriptive retrospective review of the epidemiological descriptions of over 80 deaths at a single hospital in Wuhan in the first month of the epidemic. as such it is an informative article. There are a few issues of note that need to be addressed: There is no definition of "severe Illness". Results section paragraph 2 line 4 77/82 were admitted with severe illness. Response: The definition has been added in the revised manuscript. 2. Line 4 of paragraph 2 of Results. Incubation time is unclear how it can be calculated. The definition in method noted this calculation to be from time of contact of transmission exposure to date to symptoms. Only 2 patients reported exposure so is incubation time calculated for only those. If so, I don't find it very informative or helpful. Response: Yes, the situation at the time was too difficult to accurately trace and calculate the incubation period of each patient. Maybe, patients actually had exposure, but they did not acknowledge contact with patients confirmed with SARS-CoV-2 infection. So, we delete the data for the median incubation time (Page 11; Table 1). 3. Table 1 Comorbidity - first listing is "ALL" Does that mean ANY? Not clear what that means. Response: “All” means patients having any one or more comorbidities. We have changed “All” to “Any” (Table 1). 4. Table 1 Comorbidity - please define disease of reduced immunity- is this Collagen vascular disease> is this HIV? what does this mean? Response: It means abnormal blood examination for cellular immune or humoral immune indexes (Table 1). 5. Table 3 needs clarification and some editing...right now the list is just too long and difficult to find your way through--for example it notes Neutrophil count (is that a mean??) then lists % with very low and very high. This was the same for every value given. There must be an easier clearer way to present this data. Response: Neutrophil count is that a median (IQR). In fact, in all Tables data are presented as median (IQR), or n/N (%), where N represents the total number of patients with COVID-19 with available data. Please see the footnotes affiliated with table 3. To present clearly, “treatment” and “survival time” in table 3 have been separated to Supporting Information part as S2 Table at the end of the manuscript. 6. Table 3 notes radiographic data in the table, but it really lists only Bilateral infiltrates at 100% of patients. This would be easier to be removed from the table and listed at the time of the statement o "severe illness on presentation - is this in fact what you meant? Response: Bilateral infiltrates at 100% of patients are radiographic findings, did not equal severe illness on presentation. To present clearly, we delete this data in Table 3. 7. Table 3 what is acquired infection? nosocomial infection during admission? Response: Yes, it means nosocomial infection during admission. 8. The surprise is that only 17% of patients go to MICU --- this appears first in the table 3 and then later there is a brief mention of this in the discussion. This is important and needs to move up much sooner in your paper. 83% of deaths never received Critical Care Support due to the overwhelming of your system. Only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. This all speaks to the overwhelming of the system and needs to be highlighted. You might look to see if the patients who did make it into the MICU were any different than the ones who did not? Response: The actual situation at the time was that the hospital was designated by Wuhan government as the COVID 19-designated hospital for severe cases, but the original 16 ICU beds were apparently not enough, medical staff and ventilators were extremely insufficient, and only 17% of patients go to MICU. Accordingly, there was a high mortality rate. After February 14th, as medical teams and supplies from all over the country went to and aid Wuhan, all the general wards in the hospital were transformed into ICUs and equipped with sufficient medical staff and equipment. After that, the mortality rate gradually declined. Thus, we highlighted the situation of the overwhelming of our medical system in Abstract. 9. What antiviral medications were given? Table 3 again. Response: From the end of January to early February, few suitable antiviral drugs for severe patients are available. We tried LianHuaQingWen Capsule, Abidor, Ribavirin or Oseltamivir, but none seemed to have explicit effect. Attachments Attachment Submitted filename: Response to Reviewers.doc https://doi.org/10.1371/journal.pone.0235458.r002
17 Jun 2020 Decision Letter - Xia Jin, Editor Clinical characteristics of 82 cases of death from COVID-19 PONE-D-20-07999R1 Dear Dr. wang, 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, Xia Jin, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0235458.r003
Formally Accepted
29 Jun 2020 Acceptance Letter - Xia Jin, Editor PONE-D-20-07999R1 Clinical characteristics of 82 cases of death from COVID-19 Dear Dr. Wang: 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. Xia Jin Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0235458.r004

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