Risk factors for mortality in COVID-19 patients in sub-Saharan Africa: A systematic review and meta-analysis

Ben Bepouka; Nadine Mayasi; Madone Mandina; Murielle Longokolo; Ossam Odio; Donat Mangala; Marcel Mbula; Jean Marie Kayembe; Hippolyte Situakibanza

doi:10.1371/journal.pone.0276008

Peer Review History

Original SubmissionDecember 10, 2021
23 Jun 2022 Decision Letter - Jianhong Zhou, Editor PONE-D-21-36467 Risk factors for in-hospital mortality in COVID-19 patients in sub-Saharan Africa: A systematic review and meta-analysis PLOS ONE Dear Dr. Bepouka, 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. Specifically, the reviewer mentioned a couple of concerns in Results section including a likely miscalculation in the mortality numbers. Please have all the comments addressed point-by-point. Please submit your revised manuscript by Jul 31 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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During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author. - https://pubmed.ncbi.nlm.nih.gov/34238232/ - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06369-0 - https://pubmed.ncbi.nlm.nih.gov/33075534/ - https://www.frontiersin.org/articles/10.3389/fphys.2021.665064/full - https://link.springer.com/article/10.1007/s11255-020-02740-3?code=aa12583d-3699-4ff6-8f1f-78915123c553&error=cookies_not_supported - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06536-3 We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. 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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: Methodology: The paper is well written and the methodology of the search strategy sound. The paper is relevant and timely and provides information from subSaharan Africa that is sadly lacking Results: The mortality of different COVID-19 variants is likely to be different. Also the mortality of infected individuals is likely to be affected by vaccination rates. I believe Table 1 needs to have the time period of study, and perhaps a comment (in table 2 as to the vaccination status during the period of study. Next I am surprised by your mortality rate of 3%. I agree table 1 shows 43598 cases of Covid-19 from the relevant countries but I calculated from your percentage mortality figures and got 2555 deaths which is 5.8%. I think to clarify you need a column that includes the number of deaths as well as the mortality percent. Table 1 should probably include also the source of the cohort of cases - eg community, hospital admitted and I think the mortality is always going to be different. Table 2 does try to describe the source of cases included. I think you need to separate the mortality of cases treated in the community from those treated in hospital. This would explain some of the significant variation in your mortality rates. Risk factors: I thought this was a very informative section. Discussion: From the countries included in the twelve studies what are the WHO reported numbers and mortality rates from these cases and how do they differ from the results in your meta-analysis and why? ****** 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: Professor David A Watters ******** [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". 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Revision 1
30 Jul 2022 Author Response TO THE ACADEMIC EDITOR 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. We follow the recommendations of the link above for example We Used Level 1 heading for all major sections and Bold type, 18pt font; We cite figures as fig 1, fig 2, etc 2. Please include a caption for figures 5 to 11. We included captions for figures 5 to 11 3. 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. We included captions for supporting Information files at the end of the manuscript and update in-text citations 4. Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author. - https://pubmed.ncbi.nlm.nih.gov/34238232/ - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06369-0 - https://pubmed.ncbi.nlm.nih.gov/33075534/ - https://www.frontiersin.org/articles/10.3389/fphys.2021.665064/full - https://link.springer.com/article/10.1007/s11255-020-02740-3?code=aa12583d-3699-4ff6-8f1f-78915123c553&error=cookies_not_supported - https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06536-3 We changed the majority of sentences in the introduction and results section, we paraphrased sentences in discussions to avoid significant text overlap between our submission and the following previously published works. TO THE REVIEWER Results: 1.I believe Table 1 needs to have the time period of study, and perhaps a comment (in table 2 as to the vaccination status during the period of study. We add the time period of study and the vaccination status during the period of study in table 2. 2. Next I am surprised by your mortality rate of 3%. I agree table 1 shows 43598 cases of Covid-19 from the relevant countries but I calculated from your percentage mortality figures and got 2555 deaths which is 5.8%. I think to clarify you need a column that includes the number of deaths as well as the mortality percent. Thank you, dear reviewer, for making this calculation. Indeed, our mortality of 3% was wrong. And after reviewing in depth the mortality rates of all countries, we also found that there was a transcription error of the mortality rate values in the Jaspard et al study which was actually 5% instead of 29% (see revised table 1). And we added a column for the number of deaths as recommended and after recalculating the total number of deaths was 2103, recalculating the mortality rate is 4.8%. That's why I didn't calculate with the software anymore and removed the figure number 2 but calculated as you did to be more sure. Thank you very much for this 3. Table 1 should probably include also the source of the cohort of cases - eg community, hospital admitted and I think the mortality is always going to be different. We have included in Table 1 the source of the cohort of cases. And indeed, the mortality was different depending on whether the case was hospitalized or community 4. Table 2 does try to describe the source of cases included. I think you need to separate the mortality of cases treated in the community from those treated in hospital. This would explain some of the significant variation in your mortality rates. Table 2 describes the source of cases included in the column of setting 5. Risk factors: I thought this was a very informative section. Thank you Discussion: 6. From the countries included in the twelve studies what are the WHO reported numbers and mortality rates from these cases and how do they differ from the results in your meta-analysis and why? We compared the mortality obtained in our included studies and the mortality of the countries from which these studies came according to WHO, and we found huge differences in countries where the cases were only hospitalized but not a big difference in countries where community cases were also included. Below you can see the paragraph we added in the discussion: The mortality prevalence of 4.8% in our study is higher than the mortality reported by the WHO. The reason for this is that the majority of the included patients in our meta-analysis were hospitalized, and in some included studies, the proportion of severe and critical patients was very high. The emergence of variants of concern may also influence case numbers and mortality, although almost all of the included studies were conducted in the first wave when these variants were not yet formally reported. Patient mortality in the DRC ranged from 13-29% versus 1.5% according to WHO data. In Ghana, mortality was 16% versus 0.87% according to WHO data. In Nigeria, mortality ranged from 3.3 to 9% versus 1.2% according to WHO data. In these countries, our meta-analysis shows high prevalence because most of the included patients are hospitalized, with a high proportion of severe cases. Mortality in South Africa and Ethiopia was close to WHO data (0.8 and 2.8 versus 2.5 and 1.5) because the studies included in these two countries also included cases from the community [1] Attachments Attachment Submitted filename: RESPONSE TO REVIEWERS.docx https://doi.org/10.1371/journal.pone.0276008.r002
25 Aug 2022 Decision Letter - Alejandro Piscoya, Editor PONE-D-21-36467R1Risk factors for in-hospital mortality in COVID-19 patients in sub-Saharan Africa: A systematic review and meta-analysisPLOS ONE Dear Dr. Bepouka, 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 Oct 09 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. 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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: All comments have been addressed Reviewer #2: All comments have been addressed ******** 2. Is the manuscript technically sound, and do the data support the conclusions? 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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 ****** 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: (No Response) Reviewer #2: 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 paper is improved and you have answered the comments from my earlier review other than a clearer calculation of the hospitalised and community mortality rates (see below). Study selection P14: There is an error in your numbers for the cases found and excluded: "found 34263 articles. After eligibility criteria, 34491 were excluded" - you have excluded more articles than you found. There is a miscalculation here. Table 2: Given none of the studies reported vaccination status, I suggest you change the table title to risk factors and leave out the vaccination status from the actual table (originally, I thought you may have a mix of vac status but all studies did not provide this). I don't think the vaccination status column is relevant given you have stated in the text and could do in a table footnote that none of the studies reported vaccination status. This can then be discussed as it would become increasingly relevant now that vaccinations are available. I realise that some of the papers included both hospitalised and community patients and perhaps did not state what the mortality of each group was separately. I still think it would be worth in the text stating what the mean mortality and range was of the patients who were hospitalised and, if possible, those that were known only to be treated or diagnosed in community but did not require admission. You will need to leave some studies out of this calculation but your hospitalised patient only studies suggest the mortality ranges from 4-29% which means hospitalisation = much higher mortality rate than 4.8%. This would be worth commenting on. Table 1: I make the mortality rate from your hospitalised only studies 7.3% (439/5972) but some of the combined studies may also have stated the mortality rates for hospitalised and community patients separately. I would suggest reorganising table 1 to show all the hospitalised only studies separately with totals compared with the combined studies. Reviewer #2: Dear Author I have checked the manuscript and you have addressed all the queries raised by the previous reviewers satisfactorily. So I have no comment to offer bye ****** 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 ******** [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.0276008.r003
Revision 2
31 Aug 2022 Author Response Dear academic editor and reviewer, thank you very much for your comments and corrections which help to improve the quality of our manuscript. To the reviewer: Find the different corrections we could make according to your remarks: Study selection P14: There is an error in your numbers for the cases found and excluded: "found 34263 articles. After eligibility criteria, 34491 were excluded" - you have excluded more articles than you found. There is a miscalculation here. it is true that there was an error in the calculation, the corrected sentence is: In the PRISMA flowchart, we can see the approach used for the document search. Initially, we found 34263 articles. After eligibility criteria, 34251 were excluded. Of the excluded studies, 5010 articles were recorded after duplicates were removed, 4890 were perceived as unrelated searches, and 108 articles met the exclusion criteria. Finally, 12 published articles were included (Fig 1). Table 2: Given none of the studies reported vaccination status, I suggest you change the table title to risk factors and leave out the vaccination status from the actual table (originally, I thought you may have a mix of vac status but all studies did not provide this). I don't think the vaccination status column is relevant given you have stated in the text and could do in a table footnote that none of the studies reported vaccination status. This can then be discussed as it would become increasingly relevant now that vaccinations are available. We removed the vaccination status from the title and the table and we have placed a table footnote that none of the studies reported vaccination status. And we discussed this in the discussion like this: None of the studies reported vaccination status. The included studies were conducted in the first wave when vaccination was not yet effective. Vaccination could help reduce this high inpatient mortality, especially if vaccination coverage was high. In the literature, there is evidence of the efficacy of COVID-19 vaccines against severe forms and a reduction in mortality. Although most doses of COVID-19 vaccines have been administered in high and middle-income countries. The efficacy of the vaccines has been demonstrated in several countries where, for example, the efficacy of the two doses was 92%, 96%, and 89%, respectively, in Israel, the USA, and the UK [50]. But in Africa, up to the end of 2021, vaccination coverage was only 17% [51]. I realise that some of the papers included both hospitalised and community patients and perhaps did not state what the mortality of each group was separately. I still think it would be worth in the text stating what the mean mortality and range was of the patients who were hospitalised and, if possible, those that were known only to be treated or diagnosed in community but did not require admission. You will need to leave some studies out of this calculation but your hospitalised patient only studies suggest the mortality ranges from 4-29% which means hospitalisation = much higher mortality rate than 4.8%. This would be worth commenting on. Dear Reviewer, you are correct; the articles that included both inpatients and community patients did not report the mortality of each group separately. In the text we stated: The range of inpatient mortality varied from 4% to 29%, with the mean mortality of the patients who were hospitalized of 7.3% (439/5972). The range of mortality for the combined studies (combining inpatients and community-diagnosed patients) varied from 0.8 to 9%, with a mean mortality rate of 4.4% (1664/37626). Separate data on the mean and range of mortality of patients treated or diagnosed in the community but not requiring admission were not clearly available in the included studies. In the discussion, we added the sentence: In addition, considering overall mortality was 4.8%; The range of inpatient mortality was 4–29% with a mean inpatient mortality of 7.3% (439/5972). Considering the range of mortality being 4–29%, one would expect higher mortality than 4.8%. This value of 4.8% is due to the fact that it is overall mortality combining inpatients and community patients, this value of 4.8% is due to the fact that it is the overall mortality combining inpatients and community patients, whose number is not negligible. Table 1: I make the mortality rate from your hospitalised only studies 7.3% (439/5972) but some of the combined studies may also have stated the mortality rates for hospitalised and community patients separately. I would suggest reorganising table 1 to show all the hospitalised only studies separately with totals compared with the combined studies. We reorganized Table 1 by presenting all inpatient-only studies separately, comparing the totals with the combined studies. To the academic editor: the references added to the discussion section are the following: 50. Tregoning JS, Flight KE, Higham SL, Wang Z, Pierce BF. Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape. Nat Rev Immunol. 2021 Oct;21(10):626-636. doi: 10.1038/s41577-021-00592-1. Epub 2021 Aug 9. PMID: 34373623; PMCID: PMC8351583. 51. WHO Africa faces 470 million COVID-19 vaccine shortfall in 2021. 2021. https://www.afro.who.int/news/africa-faces-470-million-covid-19-vaccine-shortfall-2021. Accessed August 28, 2022. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0276008.r004
27 Sep 2022 Decision Letter - Alejandro Piscoya, Editor Risk factors for mortality in COVID-19 patients in sub-Saharan Africa: A systematic review and meta-analysis PONE-D-21-36467R2 Dear Dr. Bepouka, 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, Alejandro Piscoya Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0276008.r005
Formally Accepted
7 Oct 2022 Acceptance Letter - Alejandro Piscoya, Editor PONE-D-21-36467R2 Risk factors for mortality in COVID-19 patients in sub-Saharan Africa: A systematic review and meta-analysis Dear Dr. Bepouka: 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 Alejandro Piscoya Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0276008.r006

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