Clinical outcomes and inflammatory marker levels in patients with Covid-19 and obesity at an inner-city safety net hospital

Anahita Mostaghim; Pranay Sinha; Catherine Bielick; Selby Knudsen; Indeevar Beeram; Laura F. White; Caroline Apovian; Manish Sagar; Natasha S. Hochberg

doi:10.1371/journal.pone.0243888

Peer Review History

Original SubmissionSeptember 26, 2020
7 Nov 2020 Decision Letter - Aleksandar R. Zivkovic, Editor PONE-D-20-30399 Clinical outcomes and inflammatory marker levels in patients with Covid-19 and obesity at an inner-city safety net hospital PLOS ONE Dear Dr. Hochberg, 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 Dec 22 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author Reviewer #1: It is important to put data also on diabetes patients with obesity, like glycemic control (HbA1c) and also medication before for DM, the same with hypertension what is the most drug they use regularly for hypertension Reviewer #2: This is a retrospective study with 791 hospitalized patients with Covid-19 that was evaluated clinical outcomes and inflammatory marker levels according to obesity presence or not. The main results hightlight that patients with obesity had more chance to die but not necessarely had more inflammation. However, when they analysed the variables according to the presence of diabetes and obesity or obesity without diabetes these results change. We know that this is a retrospective study and as the authors discussed causative conclusions we could not state about these observations, but it is a very intriguing result. Maybe esteatohepatitis could be the cause for these differences. I think it would be very interesting if the authors could add any comments about this. In general, it is a very interesting manuscript. Congratulations all the authors! Absolutely, it deserves to be published. Reviewer #3: This topic is not novel, the association between obesity and adverse outcomes of COVID-19 has been established However I recommend publication of the article, as it adds to the evidences about this topic The discussion is not well developed and should include all papers that have been developed about this topic notably https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314342/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513689/ ******** 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: No Reviewer #2: Yes:** Simone Cristina Soares Brandão Reviewer #3: 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. 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Revision 1
24 Nov 2020 Author Response 1. The first reviewer recommended “It is important to put data also on diabetes patients with obesity, like glycemic control (HbA1c) and also medication before for DM, the same with hypertension what is the most drug they use regularly for hypertension”. a. Unfortunately, due to the retrospective nature of the study, we were reliant on provider history-taking and orders. Many of our patients seek primary care outside our hospital system and do not remember medications on admission interview, so a complete and accurate picture of this is not able to be obtained. We have previously mentioned one of the limitations as not being able to obtain HgA1c measurements, however we have added the inability to obtain accurate pre-hospital medication lists to this. 2. The second reviewer recommended “This is a retrospective study with 791 hospitalized patients with Covid-19 that was evaluated clinical outcomes and inflammatory marker levels according to obesity presence or not. The main results highlight that patients with obesity had more chance to die but not necessarily had more inflammation. However, when they analyzed the variables according to the presence of diabetes and obesity or obesity without diabetes these results change. We know that this is a retrospective study and as the authors discussed causative conclusions we could not state about these observations, but it is a very intriguing result. Maybe steatohepatitis could be the cause for these differences. I think it would be very interesting if the authors could add any comments about this. In general, it is a very interesting manuscript. Congratulations all the authors! Absolutely, it deserves to be published.” a. We have added to the discussion section the potential mechanism of this including studies of steatohepatitis in Covid-19 and in sepsis. 3. The third reviewer recommended “This topic is not novel, the association between obesity and adverse outcomes of COVID-19 has been established. However I recommend publication of the article, as it adds to the evidences about this topic The discussion is not well developed and should include all papers that have been developed about this topic notably” and listed two specific articles. a. One article brought up the relationship between higher obesity rates by country, GDP, and food supply with worse outcomes. Given the rapidly evolving nature of COVID and associated publications, many publications have come out. In order to update our paper from time of writing, we have included the recommended paper in our introduction as well as a newer meta-analysis that specifically addresses outcomes comparatively between patients with obesity and those without obesity in 35 published cohorts. We included a discussion with references on inflammatory mechanisms in obesity, which includes immune exhaustion, leptin cycling, inflammatory markers, and adipose tissue immune cells which already comprise the bulk of the review paper suggested. However, as our paper suggests a non-inflammatory component to increased mortality in COVID and obesity, we have cited a newer paper directly tying viral mechanism to adipose tissue. https://doi.org/10.1371/journal.pone.0243888.r002
1 Dec 2020 Decision Letter - Aleksandar R. Zivkovic, Editor Clinical outcomes and inflammatory marker levels in patients with Covid-19 and obesity at an inner-city safety net hospital PONE-D-20-30399R1 Dear Dr. Hochberg, 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, Aleksandar R. Zivkovic Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0243888.r003
Formally Accepted
11 Dec 2020 Acceptance Letter - Aleksandar R. Zivkovic, Editor PONE-D-20-30399R1 Clinical outcomes and inflammatory marker levels in patients with Covid-19 and obesity at an inner-city safety net hospital Dear Dr. Hochberg: 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. Aleksandar R. Zivkovic Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0243888.r004

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