Ferritin, blood urea nitrogen, and high chest CT score determines ICU admission in COVID-19 positive UAE patients: A single center retrospective study

Riyad Bendardaf; Poorna Manasa Bhamidimarri; Zainab Al-Abadla; Dima Zein; Noura Alkhayal; Ramy Refaat Georgy; Feda Al Ali; Alaa Elkhider; Sadeq Qadri; Rifat Hamoudi; Salah Abusnana

doi:10.1371/journal.pone.0269185

Peer Review History

Original SubmissionSeptember 13, 2021
25 Nov 2021 Decision Letter - Alexandra Lucas, Editor PONE-D-21-26443Ferritin, blood urea nitrogen and high chest CT score determines ICU admission in COVID-19 positive UAE patients: a single center retrospective studyPLOS ONE Dear Dr. Hamoudi, 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 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. 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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. Additional Editor Comments: One reviewer has rejected this manuscript based on prior larger studies. One reviewer has requested only minor revisions but raises some concerns. With the note we are designating this manuscript as requiring major revisions and we are asking the authors to respond to all critiques in a point by point fashion. Please reply carefully and in detail to each of the reviewers' comments in a point by point manner. [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? 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: While this is an interesting study the sample size, especially of sub analysis are very small. As a single center study the generalized applicability of these observations is limited. Some of the sub study groups have only 2 subjects and several recent publications on the same have 500 plus subjects available for analysis. Reviewer #2: This manuscript by Bendardaf and Bhamidimarri et al., proposed predictive metrics for evaluating whether patients will be admitted to the ICU based on biochemical and radiological findings. This is a retrospective analysis. These findings are of importance and global relevance and may be useful for informing medical decisions in some cases. The main concern is the small sample size (N=57). To their credit, the authors acknowledge this limitation in the manuscript, but the broader implication for such a small sample size is the potential to over-train their analysis. Essentially, if all 57 patients were used in the creation of the ROC curves, how do we know whether the identified metrics will be any good in the real world? ROC analysis is best when there is a "discovery" step followed by a "validation" step. With such a small sample size, it appears the authors have only done the "discovery" step. Can the authors reach out to another medical center to evaluate whether their patient data can be tested to validate the metrics identified here? This information might also be available from mining in the literature. The risk here is that these metrics might only be relevant to these 57 patients at University Hospital Sharjah. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). 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Revision 1
27 Feb 2022 Author Response PONE-D-21-26443 Reviewer #1: While this is an interesting study the sample size, especially of sub analysis are very small. As a single center study the generalized applicability of these observations is limited. Some of the sub study groups have only 2 subjects and several recent publications on the same have 500 plus subjects available for analysis. Answer: We thank the reviewer for the positive comments about the study and agree that the sample size might be small to arrive at solid conclusion. In order to address the sample size limitation, we included ~50 additional cases in the ICU admitted group from the single center. In total, the current study has 66 in ICU admitted group (earlier it was 17) and 40 in non-ICU admitted group. The outcome observed in the earlier small cohort were similar to larger cohort. Moreover, the accuracy for predicting the ICU admission increased to 94.2% with inclusion of additional 50 cases in ICU admitted group for cumulative radiological and biochemical parameters than the earlier cohort. The conclusions largely remained the same in both the cases (earlier and now) indicating CORADS along with ferritin and blood urea nitrogen values determines the ICU admission more accurately than considered independent. In most of the studies, more specifically in relation to COVID-19, clinical characterization from single center study was helpful in determining the factors associated with COVID-19 which was correlating with the other large cohort studies. For example the observations made in a small cohort of 60 COVID-19 patients in China (https://journals.lww.com/md-journal/Fulltext/2021/07300/A_retrospective_analysis_from_a_single_center_for.37.aspx) were parallel with the large cohort of 1296 patients from Brazil both being single center studies (https://journal.einstein.br/article/clinical-characteristics-and-outcomes-of-covid-19-patients-admitted-to-the-intensive-care-unit-during-the-first-year-of-the-pandemic-in-brazil-a-single-center-retrospective-cohort-study/) In addition, meta-analysis conducted on 58 independent studies on COVID-19 showed the similar findings for the biochemical parameters from the current study (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444810/). Reviewer #2: This manuscript by Bendardaf and Bhamidimarri et al., proposed predictive metrics for evaluating whether patients will be admitted to the ICU based on biochemical and radiological findings. This is a retrospective analysis. These findings are of importance and global relevance and may be useful for informing medical decisions in some cases. The main concern is the small sample size (N=57). To their credit, the authors acknowledge this limitation in the manuscript, but the broader implication for such a small sample size is the potential to over-train their analysis. Essentially, if all 57 patients were used in the creation of the ROC curves, how do we know whether the identified metrics will be any good in the real world? ROC analysis is best when there is a "discovery" step followed by a "validation" step. With such a small sample size, it appears the authors have only done the "discovery" step. Can the authors reach out to another medical center to evaluate whether their patient data can be tested to validate the metrics identified here? This information might also be available from mining in the literature. The risk here is that these metrics might only be relevant to these 57 patients at University Hospital Sharjah. Answer: We thank the reviewer for taking time to thoroughly review the article and identify the importance of the study. As mentioned, we do agree about the sample size and hence addressed it by collecting information from additional 50 cases from ICU admitted group. In total, the current study has 66 in ICU admitted group (earlier it was 17) and 40 in non-ICU admitted group. The biochemical characteristics and symptoms correlated with the earlier smaller cohort. The important findings regarding cumulative use of CORADS along with ferritin and blood urea nitrogen values to determine ICU admission holds true even upon increasing the samples size. In fact, the current cohort showed an increase in accuracy to 94.2% when all the three parameters were combined to determine ICU admission. This indicated that the observations made in 57 samples were also relevant in 106 samples and are in coherence with other such studies performed at different centers. In order to assess the findings in other study, we looked for similar studies but information on all the variables were not provided to pair the samples with corresponding CORADS score and biochemical characteristics. Hence, we had to rely mostly on the conclusions from independent studies. However, most of the observations made in our study reflected in other COVID-19 related studies which were also discussed in the article to correlate the findings from similar studies in another cohort. Attachments Attachment Submitted filename: Response to reviewers.DOCX https://doi.org/10.1371/journal.pone.0269185.r002
17 May 2022 Decision Letter - Alexandra Lucas, Editor Ferritin, blood urea nitrogen and high chest CT score determines ICU admission in COVID-19 positive UAE patients: a single center retrospective study PONE-D-21-26443R1 Dear Dr. Hamoudi, 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, Alexandra Lucas Academic Editor PLOS ONE Additional Editor Comments (optional): We apologize for the delayed response, the reviewers' reviews were delayed. We had requested a re review from reviewer #2 but they had suggested minor revisions and have not responded. You have responded appropriately to the comments from the reviewers and we believe this manuscript is acceptable for publication. We thank you for your patience and we are pleased to accept your manuscript. https://doi.org/10.1371/journal.pone.0269185.r003
Formally Accepted
10 Jul 2022 Acceptance Letter - Alexandra Lucas, Editor PONE-D-21-26443R1 Ferritin, blood urea nitrogen, and high chest CT score determines ICU admission in COVID-19 positive UAE patients: a single center retrospective study Dear Dr. Hamoudi: 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 Alexandra Lucas Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0269185.r004

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