Clinical and pharmacological factors associated with mortality in patients with COVID-19 in a high complexity hospital in Manaus: A retrospective study

Rebeka Caribé Badin; Robson Luís Oliveira de Amorim; Alian Aguila; Liliane Rosa Alves Manaças

doi:10.1371/journal.pone.0280891

Peer Review History

Original SubmissionAugust 24, 2022
24 Nov 2022 Decision Letter - Benjamin M. Liu, Editor PONE-D-22-23301Clinical and pharmacological factors associated with mortality in patients with COVID-19 in a high complexity hospital in Manaus: a retrospective studyPLOS ONE Dear Dr. Badin, 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 Jan 1, 2023. 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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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 ******** 2. 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: Badin R. et al reported a retrospective study of clinical and pharmacological factors with mortality in patients with COVID-19 in a high complexity hospital in Manaus, Brazil. They included patients from a reference hospital belonging to the Brazilian public health system, in Manaus, from March 2020 to July 2021 and analyzed the clinical and demographic features, the presence of comorbidities, and pharmacotherapeutic management in patients hospitalized for diagnosis of COVID-19, in addition to identifying predictive factors for mortality. After multivariate logistic regression analysis, age, need for mechanical ventilation, length of hospital stay, and penicillin use were associated with death. The topic is interesting and has important role in clinical application. However, some issues are still needed to addressed: 1. As we all know, different genotypes of SARS-CoV-2 has different ability of infection and pathogenesis. The authors should also analyze the genotypes influence on the mortality. 2. It is important to analyze the laboratory parameters (such as CRP, ALT, AST, pCO2, pO2, etc.), and radiological findings at admission with relationship with mortality. 3. It is also important to analyze the demographic and laboratory parameters to find multivariate predictors of in-hospital mortality of patients with COVID-19. 4. Please check and modify the format of the references one by one. ****** 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: Kuanhui Xiang ******** [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.docx https://doi.org/10.1371/journal.pone.0280891.r001
Revision 1
8 Jan 2023 Author Response Dear Dr. Chenete and reviewers, We are pleased to forward the responses regarding the observations by the reviewers of the manuscript “Clinical and pharmacological factors associated with mortality in patients with COVID-19 in a high complexity hospital in Manaus: a retrospective study”, co-authored by Rebeka Caribé Badin, Robson Luís Oliveira de Amorim, Alian Aguila, Liliane R. A. Manaças, which we submit for publication in Plos one. 1. As we all know, different genotypes of SARS-CoV-2 has different ability of infection and pathogenesis. The authors should also analyze the genotypes influence on the mortality. During the study period, the genotypic characterization of the SARS-COV-2 strains was carried out by sampling, making it impossible to analyze the impact of this variable on the mortality rate. However, data from the literature (ref: 23-25) and from the epidemiological bulletin of the city of Manaus (ref: 7) report the predominance of the B.1.195 variant in the first wave of infection (June and November 2020) and the P.1 variant in the second wave (December 2020 and February 2021). This information is described in the article discussion. 2. It is important to analyze the laboratory parameters (such as CRP, ALT, AST, pCO2, pO2, etc.), and radiological findings at admission with relationship with mortality. Recognizing that laboratory and image parameters are also extremely relevant to guide the clinical decision and considering the reviewer's suggestion, we included in the study the analysis of the AST, ALT, and oxygen saturation variables. However, due to the lack of data in the patient’s medical records, it was not possible to include the other suggested variables in the study. The analysis of the collected parameters was incorporated into the reviewed version of the manuscript. 3. It is also important to analyze the demographic and laboratory parameters to find multivariate predictors of in-hospital mortality of patients with COVID-19. All of parameters included in the research (demographic, clinical, laboratory, and pharmacological) were statistically analyzed. For quantitative variables, the Kolmogorov-Smirnov Normality test was applied. Student's t-test (Normal Distribution) and Mann-Whitney (Non-Normal Distribution) were used to compare two groups (survivors and non-survivors). Categorical variables were shown in percentages or absolute values , and the Chi-Square Test and Fisher's Exact Test were used to verify the association between categorical variables. The statistically significant variables identified in the univariate analysis were included in the multivariate logistic regression analysis (model 1) (S1). However, some variables did not prove to be statistically significant in model one, such as the need for ICU, the use of corticosteroids, antimicrobials, anticoagulants, antifungals, and an antibiotic class of glycopeptides. Thus, a second multivariate logistic regression analysis model was done using the reverse stepwise approach until all variables were significant (model 2) (table 3). In the article, we rewrote this information in the topic “characteristics associated with mortality” to clarify the multivariate logistic regression analysis. 4. Please check and modify the format of the references one by one. We checked and corrected the references, according to the journal's instructions. For this purpose, we use the Zotero program. Attachments Attachment Submitted filename: responsestoreviewer.docx https://doi.org/10.1371/journal.pone.0280891.r002
11 Jan 2023 Decision Letter - Benjamin M. Liu, Editor Clinical and pharmacological factors associated with mortality in patients with COVID-19 in a high complexity hospital in Manaus: a retrospective study PONE-D-22-23301R1 Dear Dr. Badin, 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, Benjamin M. Liu, MBBS, PhD, D(ABMM), MB(ASCP) Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes ****** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes ****** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The answers provided by the authors are satisfy for me. they also re-analyzed the data and made it more accurate. I have no any other questions. ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes: no ******** https://doi.org/10.1371/journal.pone.0280891.r003
Formally Accepted
16 Jan 2023 Acceptance Letter - Benjamin M. Liu, Editor PONE-D-22-23301R1 Clinical and pharmacological factors associated with mortality in patients with COVID-19 in a high complexity hospital in Manaus: a retrospective study Dear Dr. Badin: 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. Benjamin M. Liu Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0280891.r004

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