Outcomes of different steroid dosing regimens in critical Covid-19 pneumonia at a Kenyan hospital: A retrospective cohort study

John Otieno Odhiambo; Jasmit Shah; Nancy Kunyiha; Charles Makasa; Felix Riunga

doi:10.1371/journal.pone.0307265

Peer Review History

Original SubmissionAugust 8, 2023
21 Dec 2023 Decision Letter - Robert Jeenchen Chen, Editor PONE-D-23-24666OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDYPLOS ONE Dear Dr. Odhiambo, 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 revise. Please submit your revised manuscript by Feb 04 2024 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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Please also provide details on how you will ensure persistent or long-term data storage and availability. [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: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No 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 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: Odhiambo J.O. and collaborators performed a single center retrospective observational study to investigate the effect of different posology of corticosteroids (i.e., dexamethasone 6 mg vs. higher equivalent dosages) in patients suffering from critical COVID-19 pneumonia admitted to ICU of the Aga Khan Hospital in Nairobi, Kenya. I personally worked in a European COVID ICU during the pandemic, and it was very complicated and stressful. I imagine working in a low and middle-income country ICU in such a situation could be exhausting; thus, I would like to thank you for conducting this research effort, and I hope this review may help you. The primary outcome of the study was mortality. Secondary outcomes were the occurrence of superinfections, dysglycemia, and duration of ICU length of stay. Two-hundred-eighty-eight patients entered the analysis. 48% received dexamethasone 6 mg; 52% higher dosages. Overall, 45.5% of patients died. No difference in mortality was observed in the two groups (43.7% vs. 47.9%, p=0.549). Higher corticosteroid dosages seemed to be associated with a higher incidence of dysglycemia and superinfection events. The authors have provided a description of an extensively studied topic but considered a population rarely enrolled in trials and studies. Indeed, the major strength of this work is the completely African population included. This aspect, in my opinion should be underlined, both in the title, as well as in the abstract. Nevertheless, the manuscript, in its current form, requires some improvements and presents a lot of methodological issues and limitations that should be thoroughly addressed: � Follow STROBE guidelines to report observational study results, as required by the Journal publication criteria. � Please specify better the primary outcome: did you assess ICU mortality, hospital mortality, or 28-day mortality? Moreover, I would suggest adding the primary outcome result to the main text as well as in the table. � Please, it could be interesting and could improve the quality of the manuscript to report 1) at least a score or parameters of illness severity (i.e., P/F ratio, Respiratory Rate, SOFA or SAPS score…); 2) the number of patients who needed mechanical ventilation; 3) the kind of steroid administered; 4) the timing of corticosteroid therapy starting compared to ICU admission. � Univariate statistic tests used are completely described, but I would suggest adjusting for possible confounders (i.e., age, sex, comorbidities, the severity of illness) for a better evaluation of steroid dosage impact on outcome. Moreover, if data permits, try to perform a survival analysis (and try to construct a Kaplan- Meier curve figure). � I would suggest reporting outcome measures in the outcome results section, not in the population characteristic section. � In the limitation section of the discussion, you stated that missing data may have influenced the results. Please report the number of missing data for each variable. � I would suggest reporting Table 1, joined with Table 2, and reporting percentage of subjects in Table 2 columns. Reviewer #2: The study is good but, being a retrospective study it has its own limitations as has been pointed by the authors.A few questions for the authors- 1) They have mentioned high dose of steroids as any dose more than 6 mg dexamethasone, were patients on any other steroids like prednisone, methylprednisolone?When were the steroids started in these patients, as in within how many days of onset of symptoms? 2) Was there any comparison between the survivors and non survivors in terms of oxygen requirements, ventilators-NIV or invasive? 3) Was there any correlation between the d Dimer levels amongst the survivors and non survivor groups? 4) How many patients were on Remdesevir considering that these were the more severe cases and was there any correlation on this? 5)How many of these patients also received LMWH or oral anticoagulants and did this affect the outcome of the study? 6) How many patients underwent a bronchoscopy and BAL for the diagnosis of pneumonia? Thank you. ****** 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: Vittorio Scaravilli, MD 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.0307265.r001
Revision 1
5 Feb 2024 Author Response Response to Reviewer’s Comments PLOS ONE OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDY Thank you for the comments. Please find below the responses to both reviewers’ comments. Reviewer 1 Reviewer #1: Odhiambo J.O. and collaborators performed a single center retrospective observational study to investigate the effect of different posology of corticosteroids (i.e., dexamethasone 6 mg vs. higher equivalent dosages) in patients suffering from critical COVID-19 pneumonia admitted to ICU of the Aga Khan Hospital in Nairobi, Kenya. I personally worked in a European COVID ICU during the pandemic, and it was very complicated and stressful. I imagine working in a low and middle-income country ICU in such a situation could be exhausting; thus, I would like to thank you for conducting this research effort, and I hope this review may help you. The primary outcome of the study was mortality. Secondary outcomes were the occurrence of superinfections, dysglycemia, and duration of ICU length of stay. Two-hundred-eighty-eight patients entered the analysis. 48% received dexamethasone 6 mg; 52% higher dosages. Overall, 45.5% of patients died. No difference in mortality was observed in the two groups (43.7% vs. 47.9%, p=0.549). Higher corticosteroid dosages seemed to be associated with a higher incidence of dysglycemia and superinfection events. The authors have provided a description of an extensively studied topic but considered a population rarely enrolled in trials and studies. Indeed, the major strength of this work is the completely African population included. This aspect, in my opinion should be underlined, both in the title, as well as in the abstract. Response: We have revised and added “At a Kenyan Hospital” in the title. Nevertheless, the manuscript, in its current form, requires some improvements and presents a lot of methodological issues and limitations that should be thoroughly addressed: • Follow STROBE guidelines to report observational study results, as required by the Journal publication criteria. Response: Thank you. We have attached the STROBE Checklist and submitted as per the criteria. • Please specify better the primary outcome: did you assess ICU mortality, hospital mortality, or 28-day mortality? Moreover, I would suggest adding the primary outcome result to the main text as well as in the table. Response: The primary outcome was ICU Mortality and we have edited the manuscript accordingly. • Please, it could be interesting and could improve the quality of the manuscript to report 1) at least a score or parameters of illness severity (i.e., P/F ratio, Respiratory Rate, SOFA or SAPS score…); 2) the number of patients who needed mechanical ventilation; 3) the kind of steroid administered; 4) the timing of corticosteroid therapy starting compared to ICU admission. Response: I agree, this could improve the quality of the study. However, we did not collect data on the different scoring systems. Additionally, we only included the steroid doses in dexamethasone equivalence but not the specific steroids used. • Univariate statistic tests used are completely described, but I would suggest adjusting for possible confounders (i.e., age, sex, comorbidities, the severity of illness) for a better evaluation of steroid dosage impact on outcome. Moreover, if data permits, try to perform a survival analysis (and try to construct a Kaplan-Meier curve figure). Response: Unfortunately, we did not collect survival data and thus it was beyond the scope of this study to do Kaplan Meier and survival analysis. • I would suggest reporting outcome measures in the outcome results section, not in the population characteristic section. Response: We have tried to edit the manuscript accordingly. • In the limitation section of the discussion, you stated that missing data may have influenced the results. Please report the number of missing data for each variable. Response: Thank you. We have included this in the limitation section. Only five patients were excluded from the study due to incomplete records. • I would suggest reporting Table 1, joined with Table 2, and reporting the percentage of subjects in Table 2 columns. Response: We have retained the tables as it is on the flow of the results. Reviewer 2 Reviewer #2: The study is good but, being a retrospective study, it has its own limitations as has been pointed by the authors. A few questions for the authors- 1. They have mentioned high dose of steroids as any dose more than 6 mg dexamethasone, were patients on any other steroids like prednisone, methylprednisolone? When were the steroids started in these patients, as in within how many days of onset of symptoms? Response: Yes, other types of steroids were used but in the data collection tool we only included steroid doses which were all converted to dexamethasone into dexamethasone equivalence. 2. Was there any comparison between the survivors and non survivors in terms of oxygen requirements, ventilators-NIV or invasive? Response: Thank you for this. This may have been a good comparison to do. All the patients included in the study were on ventilatory support, but we did not include the specific type of support. 3. Was there any correlation between the d Dimer levels amongst the survivors and non survivor groups? Response: No data was collected on D-dimer levels or any other coagulation parameters. 4. How many patients were on Remdesevir considering that these were the more severe cases and was there any correlation on this? Response: This was beyond the scope of our study and has been included as part of the limitations. 5. How many of these patients also received LMWH or oral anticoagulants and did this affect the outcome of the study? Response: We did not include data on the anticoagulation. However, as per the hospital policy and guidelines, all patients admitted to critical care unit are put on prophylactic anticoagulation or treatment doses in case of evidence of thrombosis unless there are contraindications. 6. How many patients underwent a bronchoscopy and BAL for the diagnosis of pneumonia? Response: Thank you for this. Unfortunately, this was beyond the scope of our study. Attachments Attachment Submitted filename: PLOS ONE response letter - John.docx https://doi.org/10.1371/journal.pone.0307265.r002
17 Mar 2024 Decision Letter - Robert Jeenchen Chen, Editor PONE-D-23-24666R1OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDYPLOS ONE Dear Dr. Odhiambo, 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 revise. Please submit your revised manuscript by May 01 2024 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, Robert Jeenchen Chen, MD, MPH 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.] 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: (No Response) Reviewer #2: All comments have been addressed Reviewer #3: (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 #1: No Reviewer #2: Yes Reviewer #3: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes Reviewer #3: 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: No Reviewer #2: Yes Reviewer #3: 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 Reviewer #2: Yes Reviewer #3: 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: Unfortunately, the authors, despite the changes in the manuscript were not able to address any of the instance I raised. Reviewer #2: All comments have been addressed to satisfaction and the article can be accepted if found to be suitable for publication by the editor. Reviewer #3: It is difficult to conclude that high doses of steroids do not influence the prognosis. Can you compare the data that can assess the severity of the 2 groups? Particularly saturation at admission and during progression. or add this mention to the limitations of this study. ****** 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: No Reviewer #2: No Reviewer #3: Yes: Abdelbassat Ketfi ******** [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.0307265.r003
Revision 2
8 Apr 2024 Author Response Response to Reviewer’s Comments PLOS ONE OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDY Thank you for the comments. Please find below the responses to both reviewers’ comments. Reviewer #1: Unfortunately, the authors, despite the changes in the manuscript were not able to address any of the instance I raised. Response: We appreciate the comments and suggestions from Reviewer 1. Some of the suggestions such as reporting at least a score or parameters of illness severity (i.e., P/F ratio, Respiratory Rate, SOFA or SAPS score…) or performing survival analysis was beyond the scope of the current project as the different data was not collected. Furthermore, we attached the STROBE guidelines to report the observational study as requested. We tried to address as much as possible and edited the manuscript accordingly. Reviewer #2: All comments have been addressed to satisfaction and the article can be accepted if found to be suitable for publication by the editor. Response: We appreciate the comments and suggestions from Reviewer 2. Reviewer #3: It is difficult to conclude that high doses of steroids do not influence the prognosis. Can you compare the data that can assess the severity of the 2 groups? Particularly saturation at admission and during progression or add this mention to the limitations of this study. Response: We appreciate the comments from Reviewer 3. We included all the patients with critical COVID-19 and on ventilator support as per the inclusion criteria. However, we did not collect any data on the measures of severity such as oxygen saturations. We have, therefore, added it to our limitations as you have advised. Attachments Attachment Submitted filename: PLOS ONE response letter - 8th April.docx https://doi.org/10.1371/journal.pone.0307265.r004
1 May 2024 Decision Letter - Robert Jeenchen Chen, Editor PONE-D-23-24666R2OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDYPLOS ONE Dear Dr. Odhiambo, 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 revise. Please submit your revised manuscript by Jun 15 2024 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, Robert Jeenchen Chen, MD, MPH Academic Editor PLOS ONE [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 #1: (No Response) Reviewer #2: All comments have been addressed Reviewer #3: All comments have been addressed Reviewer #4: 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: Partly Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: No ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: No Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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 Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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 #1: Yes Reviewer #2: Yes Reviewer #3: Yes Reviewer #4: 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 choice not to collect further descriptive data from the two cohorts, unfortunately, is not agreeable. The severity data of the pathology wouldn't have had solely a descriptive purpose but could have helped the authors to consider possible confounders in the statistical analysis: such as whether patients who had taken higher doses of steroids were the most severe and thus at higher risk of superinfection Reviewer #2: All queries have been addressed to satisfaction and may be considered for publication if the article meets the other requirements. Reviewer #3: (No Response) Reviewer #4: the points mentioned by the authors in the limitation are very important for the study. because of these deficiencies, it is not suitable for publication. also the discussion section is inadequate ****** 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: No Reviewer #2: No Reviewer #3: Yes: Abdelbassat Ketfi Reviewer #4: 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.0307265.r005
Revision 3
14 Jun 2024 Author Response 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: (No Response) Reviewer #2: All comments have been addressed Reviewer #3: All comments have been addressed Reviewer #4: All comments have been addressed Response: Thank you for taking time out of your schedule to review our paper and we are happy to note that all your queries were addressed. Reviewer #1: The choice not to collect further descriptive data from the two cohorts, unfortunately, is not agreeable. The severity data of the pathology wouldn't have had solely a descriptive purpose but could have helped the authors to consider possible confounders in the statistical analysis: such as whether patients who had taken higher doses of steroids were the most severe and thus at higher risk of superinfection Response: Having realised that this would improve the quality of the manuscript as was highlighted by the reviewer, we went back and collected data on markers of severity of the disease for instance CRP and oxygen saturation at admission. Due to medical records being paper documents and also limited data available, we aimed at collecting CRP and oxygen saturation. From furtner analyses, it was evident that oxygen saturation at admission was significantly lower in the non-survivors’ group than the survivors’ group whereas as CRP was significantly lower in the high dose group as compared to the standard dose group. Reviewer #2: All queries have been addressed to satisfaction and may be considered for publication if the article meets the other requirements. Response: Thank you for taking time out of your schedule to review our paper and we are happy to note that all your queries were addressed. Reviewer #4: The points mentioned by the authors in the limitation are very important for the study. The discussion section is inadequate Response: Thank you so much for the point you have raised. We have delt with one of the major limitations which was lack of data on the markers of severity such as the level of the inflammatory markers and oxygen saturations at admission and put up an additional paragraph in the discussion section. We believe that this has improved the quality of the manuscript and hopefully accepted for publication. Attachments Attachment Submitted filename: PLOS ONE Comments- John 14th June 2024.docx https://doi.org/10.1371/journal.pone.0307265.r006
3 Jul 2024 Decision Letter - Robert Jeenchen Chen, Editor OUTCOMES OF DIFFERENT STEROID DOSING REGIMENS IN CRITICAL COVID-19 PNEUMONIA: A RETROSPECTIVE COHORT STUDY PONE-D-23-24666R3 Dear Dr. Odhiambo, 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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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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: All comments have been addressed Reviewer #3: 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 #2: Yes Reviewer #3: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes Reviewer #3: 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 #2: Yes Reviewer #3: 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 #2: Yes Reviewer #3: 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: All comments have been addressed to satisfaction and could be considered for publication if it meets the other requirements and has fulfilled the other criteria. Reviewer #3: (No Response) ****** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Formally Accepted
8 Jul 2024 Acceptance Letter - Robert Jeenchen Chen, Editor PONE-D-23-24666R3 PLOS ONE Dear Dr. Odhiambo, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, 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 customercare@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. Robert Jeenchen Chen Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0307265.r008

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