COVID-19 infections and outcomes in a live registry of heart failure patients across an integrated health care system

César Caraballo; Megan McCullough; Michael A. Fuery; Fouad Chouairi; Craig Keating; Neal G. Ravindra; P. Elliott Miller; Maricar Malinis; Nitu Kashyap; Allen Hsiao; F. Perry Wilson; Jeptha P. Curtis; Matthew Grant; Eric J. Velazquez; Nihar R. Desai; Tariq Ahmad

doi:10.1371/journal.pone.0238829

Peer Review History

Original SubmissionMay 7, 2020
18 Aug 2020 Decision Letter - Chiara Lazzeri, Editor Transfer Alert This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present. PONE-D-20-13485 COVID-19 Infections and Outcomes in a Live Registry of Heart Failure Patients Across an Integrated Health Care System PLOS ONE Dear Dr. Ahmad, 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 02 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. 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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. [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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. 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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: Caraballo C. and Collegues described the social and clinical profile, the prevalence and the predictors of outcomes of a large sample of HF patients positive to SARS-CoV-2, registered in the YALE Heart Failure Registry in Connecticut area. Being able to use a real-time registry the authors have clearly described the clinical differences of 900 symptomatic COVID+ HF patients in respect those COVID- and the predictors of poor outcomes in this subgroup of HF patients. Although some clinical data had already been confirmed elsewhere, in this study some interesting findings must be underlined: the elevated rate of death (20%) in very elderly (>85 years) HF patients with symptomatic COVID, the negative prognostic role of high burden of comorbid conditions as well as the low level of socioeconomic status. This data, together of other clinical evidences, clearly suggest how HF older frail patients should be the priority for any prevention program of vaccination or other preventive care program. Also interesting is the data concerning the positive association RAAS inhibitor drugs and prognosis; moreover this result is found in a large population of patients in whom these drugs have a high level of evidence based recommendation. Another flag finding concerns the low percentage of HF patients underwent testing for COVID, this report, in my opinion, is another important clinical alert that must be taken into account by those who have health- care system responsibilities. Thus I think that this paper, well written, deserves a good consideration for publication in the Journal accounting the aforementioned considerations. Obviously this is a retrospectively analysis but in my opinion it does not reduce significantly the clinical value. Reviewer #2: The authors assessed how many patients include in their Yale Heart Failure Registry (N=26,703). Were tested for COVID-19 and were positive . they then compare the clinical characteristics of the positive patients versus the negative ones and show that covid positive patients tend to be more geographically concentrated, an expected finding based on the characteristic of the disease. Elderly COVID-19+ patients were very likely to be admitted to the hospital and experience high rates of mortality. The study is clearly written. However, its clinical implications and novelty compared with current literature seem extremely limited. In the discussion, the authors state “This is the first report describing the impact of COVID-19 infection in a geographically contained population of heart failure patients under the purview of an integrated health care system.” I agree but is this worthwhile? Then, they state “We found that (…) those who tested positive tended to cluster around two cities—New Haven and Bridgeport, two of the cities with the lowest median household income in the state…” Again, this conforms data with most of infective disease. ****** 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: 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
20 Aug 2020 Author Response Response to Reviewer Comments Caraballo et al. PLOS ONE. RE: PONE-D-20-13485 REVIEWER #1 Caraballo C. and Colleagues described the social and clinical profile, the prevalence and the predictors of outcomes of a large sample of HF patients positive to SARS-CoV-2, registered in the YALE Heart Failure Registry in Connecticut area. Being able to use a real-time registry the authors have clearly described the clinical differences of 900 symptomatic COVID+ HF patients in respect those COVID- and the predictors of poor outcomes in this subgroup of HF patients. Although some clinical data had already been confirmed elsewhere, in this study some interesting findings must be underlined: the elevated rate of death (20%) in very elderly (>85 years) HF patients with symptomatic COVID, the negative prognostic role of high burden of comorbid conditions as well as the low level of socioeconomic status. This data, together of other clinical evidences, clearly suggest how HF older frail patients should be the priority for any prevention program of vaccination or other preventive care program. Also interesting is the data concerning the positive association RAAS inhibitor drugs and prognosis; moreover this result is found in a large population of patients in whom these drugs have a high level of evidence based recommendation. Another flag finding concerns the low percentage of HF patients underwent testing for COVID, this report, in my opinion, is another important clinical alert that must be taken into account by those who have health- care system responsibilities. Thus I think that this paper, well written, deserves a good consideration for publication in the Journal accounting the aforementioned considerations. Obviously this is a retrospectively analysis but in my opinion it does not reduce significantly the clinical value. Response: We thank the reviewer for their kind and important comments. We have incorporated them into our manuscript. We agree with the reviewer of the uttermost importance of increasing access to testing and vaccination to elderly patients with HF. We have modified the discussion section as shown below (additions underlined): Pages 13 and 14, lines 217-224: “In our cohort, we noted 33% of COVID-19+ positive patients to be ≥85 years old. These patients had hospitalization rates of approximately 90%, 36% had died at the time of this analysis, and all the rest except one patient remained hospitalized. This suggests that special importance should be given to elderly individuals with HF when discussing testing distribution and early access to preventive therapies upon availability, such as vaccination against SARS-CoV-2. This also suggests an urgent need for early goals of care discussions in elderly heart failure patients who test positive for COVID-19+ given long hospitalizations and high mortality rates despite aggressive treatment.” __________ REVIEWER #2 The authors assessed how many patients include in their Yale Heart Failure Registry (N=26,703). Were tested for COVID-19 and were positive . they then compare the clinical characteristics of the positive patients versus the negative ones and show that covid positive patients tend to be more geographically concentrated, an expected finding based on the characteristic of the disease. Elderly COVID-19+ patients were very likely to be admitted to the hospital and experience high rates of mortality. The study is clearly written. However, its clinical implications and novelty compared with current literature seem extremely limited. In the discussion, the authors state “This is the first report describing the impact of COVID-19 infection in a geographically contained population of heart failure patients under the purview of an integrated health care system.” I agree but is this worthwhile? Then, they state “We found that (…) those who tested positive tended to cluster around two cities—New Haven and Bridgeport, two of the cities with the lowest median household income in the state…” Again, this conforms data with most of infective disease. Response: We thank the reviewer for their comments, which have helped us improve our manuscript. Although everyday new data on COVID-19 is being published, its implications in patients with heart failure are still being elucidated and our study contributes to this knowledge by demonstrating early outcomes among these patients, using a health care system that facilitates outcomes detection and ascertainment in our region. We have modified the discussion to better reflect this, as shown below (additions underlined): Page 12, lines 181-183: “This is the first report describing the impact of COVID-19 infection in a geographically contained population of heart failure patients under the purview of an integrated health care system, providing insight into how such a system can be used to analyze early data on diagnosis status and outcomes ascertainment among its population.” Also, we agree that the SARS-CoV-2 transmission among individuals with low SES may be a function of higher spread of infectious diseases in general. We have added this as one of the plausible explanations of our findings (additions underlined): Page 13, lines 196-198: “The causes for this finding are multifaceted and have been hypothesized to include the disproportionate number of minorities who are exposed to COVID-19 in their roles as “essential workers” and who spread the disease to their residentially segregated communities. Also, situations associated with lower socioeconomic conditions, such as housing insecurity and access to health care barriers, can facilitate the spread of infectious diseases. Taken together, these findings suggest an urgent need for a more nuanced strategy to tackle the disparate impact of the virus across vulnerable populations, including those with heart failure who are at particularly high risk.” Attachments Attachment Submitted filename: ResponseLetter_YaleHF-COVID19_PlosOne 8.20.20.docx https://doi.org/10.1371/journal.pone.0238829.r002
26 Aug 2020 Decision Letter - Chiara Lazzeri, Editor COVID-19 Infections and Outcomes in a Live Registry of Heart Failure Patients Across an Integrated Health Care System PONE-D-20-13485R1 Dear Dr. Ahmad, 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, Chiara Lazzeri Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0238829.r003
Formally Accepted
4 Sep 2020 Acceptance Letter - Chiara Lazzeri, Editor PONE-D-20-13485R1 COVID-19 Infections and Outcomes in a Live Registry of Heart Failure Patients Across an Integrated Health Care System Dear Dr. Ahmad: 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. Chiara Lazzeri Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0238829.r004

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