Clinical characteristics and outcomes of hospitalized patients with COVID-19 in a city of South Brazil: Have they changed through the first year of the pandemic?

Henrique Demeneck; André Luiz Parmegiani de Oliveira; Julia do Carmo Machado Kneipp Lopes; Leonardo Ryoiti Matsunago; Luiza Cavalca Grupenmacher; Marcos Roberto Curcio Pereira; Rebecca Benício Stocco; Salma Ali El Chab Parolin; Marcia Olandoski; Cristina Pellegrino Baena

doi:10.1371/journal.pone.0286589

Peer Review History

Original SubmissionFebruary 1, 2023
20 Mar 2023 Decision Letter - Tariq Jamal Siddiqi, Editor PONE-D-23-02590Clinical characteristics and outcomes of hospitalized patients with COVID-19 in a city of south Brazil: have they changed through the first year of the pandemic?PLOS ONE Dear Dr. DEMENECK, 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 May 04 2023 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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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: Demeneck et al. conducted a prospective study titled: “Clinical characteristics and outcomes of hospitalized patients with COVID-19 in a city of south Brazil: have they changed through the first year of the pandemic?”, in which the authors described the potential changes of the clinical characteristics and outcomes of hospitalized patients during the first year of the COVID-19 pandemic in a city of south Brazil. In my opinion the manuscript can be improved by inculcating the following changes: 1. Abstract: although the authors have summarized the background, the aims, the methods, and results of their study in the abstract of the manuscript, it would improve the manuscript if the authors add a few lines regarding the conclusion of their study in the abstract as well. 2. Introduction section: although the authors have mentioned that few studies have focused on identifying the variation in clinical characteristics of hospitalized patients, it would improve the manuscript if the authors cite those studies and mention what is lacking in those studies and how this study hopes to fulfill that gap in knowledge. Furthermore, the authors should also consider adding a few lines regarding why the knowledge pertaining to variation in clinical characteristics is necessary in the first place. 3. Introduction section: “The present study investigated those characteristics and the frequencies of negative outcomes - oral intubation, ICU admission and mortality – among patients admitted to the hospital due to COVID-19 during the first year of the pandemic at two referral centers located in the city of Curitiba, south Brazil.”; the authors should consider removing these lines from the introduction section, as they are redundant. 4. Methods section: where the authors mention the names of the two hospitals, in which the study was conducted, the authors should also mention the name of the city in which the two hospitals are located. 5. Methods section: the number of included and excluded patients should be removed from the methods section of the manuscript and should be mentioned in the beginning of the results section. 6. Results section: in the methods section, the authors mentioned that for the multivariate logistic regression, sex, in addition to age and any variable with p < 0.10 in the univariate analyses were included. However, the results for the multivariate logistic regression with regards to sex have neither been reported in the manuscript nor in the corresponding figure. 7. Results section: the corresponding Odds Ratios with their respective 95% confidence intervals for each predictor variable should also be reported for the multivariate logistic regression analysis. 8. Discussion section: it would add value to the significance and relevance of the study if the authors expand upon the clinical implications of their findings in the discussion section of the manuscript. 9. The authors should consider thoroughly proofreading the manuscript, as typos and grammatical errors are present at certain places in the manuscript. ****** 6. 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Revision 1
12 Apr 2023 Author Response Thanks for the encouraging comments and the contributions to enhance the quality of our manuscript. We conducted a target review of the article and we have now clarified the points that needed attention according to your review. 1. Abstract: although the authors have summarized the background, the aims, the methods, and results of their study in the abstract of the manuscript, it would improve the manuscript if the authors add a few lines regarding the conclusion of their study in the abstract as well. Reply – Thanks for pointing out this issue. We agree that there is a lack of a conclusion for the abstract presented. We have now added it to our abstract section that reads: “Our key findings revealed that, although there were no statistically significant differences between the subgroups of hospitalized patients over time in terms of demographic characteristics and comorbidities, the course of COVID-19 was significantly more severe for patients admitted to the hospital at the end of the first year of the pandemic in Brazil”. 2. Introduction section: although the authors have mentioned that few studies have focused on identifying the variation in clinical characteristics of hospitalized patients, it would improve the manuscript if the authors cite those studies and mention what is lacking in those studies and how this study hopes to fulfill that gap in knowledge. Furthermore, the authors should also consider adding a few lines regarding why the knowledge pertaining to variation in clinical characteristics is necessary in the first place. Reply – We have now cited previous studies conducted in other locations of Brazil that evaluated the clinical characteristics of affected patients during the first year of the pandemic. We have also pointed out the relevance and innovative features of our study and its clinical implications for a better understanding of the local epidemiology of COVID-19. “Although previous studies have identified the clinical characteristics of hospitalized patients in the northeast and southeast Brazil, it has not been elucidated whether these characteristics varied through the first year of the pandemic in the country and if the time of occurrence of the hospitalization represented an independent risk factor for negative outcomes. [11,12] We aim to answer these questions as these variations may reflect changes in the prognostic factors, healthcare system burden and host-pathogen interactions at different periods of the pandemic in Brazil. Tracking these features may lead to a better understanding of how the clinical course of COVID-19 varied in our community and which temporal factors may have contributed to variations in the epidemiology of the disease at the local level”. 3. Introduction section: “The present study investigated those characteristics and the frequencies of negative outcomes - oral intubation, ICU admission and mortality – among patients admitted to the hospital due to COVID-19 during the first year of the pandemic at two referral centers located in the city of Curitiba, south Brazil.”; the authors should consider removing these lines from the introduction section, as they are redundant. Reply – We have excluded the sentence from the introduction as suggested by the reviewer. 4. Methods section: where the authors mention the names of the two hospitals, in which the study was conducted, the authors should also mention the name of the city in which the two hospitals are located. Reply- We have added the location of the hospitals. “This is a prospective study carried out in two tertiary care private hospitals located in Curitiba, South Brazil: Marcelino Champagnat Hospital and Nossa Senhora das Graças Hospital” 5. Methods section: the number of included and excluded patients should be removed from the methods section of the manuscript and should be mentioned in the beginning of the results section. Reply- This information has been added in the first paragraph of the results section of the manuscript: “A total of 1151 consecutive patients who were hospitalized during the first year of the pandemic and met inclusion criteria were analyzed, totalling to following numbers for each period: 120 (critical period 1), 120 (critical period 2), 149 (critical period 3) and 762 patients (for all non-critical periods). A total of 42 patients with incomplete medical information and those who did not agree to participate in the study were excluded.” 6. Results section: in the methods section, the authors mentioned that for the multivariate logistic regression, sex, in addition to age and any variable with p < 0.10 in the univariate analyses were included. However, the results for the multivariate logistic regression with regards to sex have neither been reported in the manuscript nor in the corresponding figure. Reply – Thank you for your diligent review. Indeed, as pointed out by the reviewer, sex was not included in the multivariate analysis since it did not have statistical significance in the univariate analysis. The previous sentence has now been replaced in the methods section: “For the multivariate model, any variable with p < 0.05 in the univariate analyses was included”. 7. Results section: the corresponding Odds Ratios with their respective 95% confidence intervals for each predictor variable should also be reported for the multivariate logistic regression analysis. Reply-The corresponding Odds Ratio and the 95% CI for each variable were added to the text. The corresponding values are also shown in the figure number 3 of the article. “The multivariate analysis showed a positive and independent association of mortality with the age ≥65 years (OR = 1.06; 95% CI = 1.05 – 1.08, p<0.001), the presence of two or more comorbidities (OR = 1.71; 95% CI = 1.01 – 2.90, p = 0.045), and admission at the critical period 3 when compared to the critical periods 1 (OR = 0.35; 95% CI = 0.16 – 0.76, p = 0.008) and 2 (OR = 0.48; 95% CI = 0.23 – 0.98, p= 0.044) of the pandemic (Figure 3).” 8. Discussion section: it would add value to the significance and relevance of the study if the authors expand upon the clinical implications of their findings in the discussion section of the manuscript. Reply - We now have discussed that the findings of our study identified the time of hospital admission as an important and independent prognostic factor for mortality due to COVID-19 among hospitalized patients. We cite the clinical relevance of such findings and suggest the role of future studies in improving our knowledge related to the epidemiology of the disease. Moreover, we have added that the knowledge pertaining to variation in clinical characteristics of the affected individuals is useful since new pandemics can occur in the future and even though healthcare workers have gained knowledge about the management of COVID-19 during the first two critical moments, the prognosis and clinical presentation of the disease deteriorated in the third studied period. “Our report identified the variations in the risk and prognostic factors of COVID-19 among hospitalized patients, providing meaningful clinical insights for a better understanding of the host-pathogen interactions during different periods of the pandemic. Even though healthcare workers gained knowledge about the management of COVID-19 during the first two critical moments of the pandemic, the prognosis and clinical presentation of the disease worsened in the third studied period. This could be attributed to an overload of challenges involving deterioration of the prognosis and clinical presentation of the health system and to the emergence of mutated viral strains due to the absence of vaccination in the population. Thus, our findings show that it is important to consider the variable time of hospital admission as an independent prognostic factor for mortality due to COVID-19 among hospitalized patients. Furthermore, our study may help local authorities to analyze the impact of different measures adopted over time such as restriction of services and the adoption of isolation measures, for controlling the transmission of the disease. Future work will aim to predict which variables (i.e. predominantly circulating virus strains, vaccination status of the population and healthcare system burden) may have influenced the variations in the epidemiology of COVID-19 in the local community and thus may have contributed to our findings. These learnings can contribute to the better management of a possible future pandemic.” 9. The authors should consider thoroughly proofreading the manuscript, as typos and grammatical errors are present at certain places in the manuscript. Reply- The manuscript was fully reviewed and proofread by Editage. Attachments Attachment Submitted filename: Response to reviewers.docx https://doi.org/10.1371/journal.pone.0286589.r002
19 May 2023 Decision Letter - Tariq Jamal Siddiqi, Editor Clinical characteristics and outcomes of hospitalized patients with COVID-19 in a city of south Brazil: have they changed through the first year of the pandemic? PONE-D-23-02590R1 Dear Dr. DEMENECK, 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, Tariq Jamal Siddiqi Academic Editor PLOS ONE Additional Editor Comments (optional): 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) ******** 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: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: (No Response) ****** 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 ******** https://doi.org/10.1371/journal.pone.0286589.r003
Formally Accepted
22 May 2023 Acceptance Letter - Tariq Jamal Siddiqi, Editor PONE-D-23-02590R1 Clinical characteristics and outcomes of hospitalized patients with COVID-19 in a city of south Brazil: have they changed through the first year of the pandemic? Dear Dr. Demeneck: 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. Tariq Jamal Siddiqi Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0286589.r004

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