Organizing pneumonia of COVID-19: Time-dependent evolution and outcome in CT findings

Yan Wang; Chao Jin; Carol C. Wu; Huifang Zhao; Ting Liang; Zhe Liu; Zhijie Jian; Runqing Li; Zekun Wang; Fen Li; Jie Zhou; Shubo Cai; Yang Liu; Hao Li; Yukun Liang; Cong Tian; Jian Yang

doi:10.1371/journal.pone.0240347

Peer Review History

Original SubmissionJune 14, 2020
24 Jul 2020 Decision Letter - Wenbin Tan, Editor PONE-D-20-17536 Organizing Pneumonia of COVID-19: Time-dependent Evolution and Outcome in CT Findings PLOS ONE Dear Dr. Yang, 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 Sep 07 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 see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. 3. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability. Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized. Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access. We will update your Data Availability statement to reflect the information you provide in your cover letter. Editor Comments: This manuscript reports dynamics of lung injuries and evolution of CT findings in COVID-19 patients. They found 1/3 of cases had complete absorption of lesions in 1-2 months; while many other patients (47 out of 67) still showed lesional residuals which may indicate a long-term pulmonary sequelae. It is a very well presented manuscript and the observational data supports the conclusion well. However, there are some minor issues for the authors to consider. (1) the format of number, such as "79(74.5%) patients were non-severe and 103(97.2%)", a space should be inserted between "number" and "(..%)". Please change throughout the entire manuscript. (2) IRB protocol of XJTU1AF2020LSK-011 is a multiple-center single IRB? This needs to be confirmed and clarified in the content since patients from multiple hospitals being involved. However, the attached copy of IRB approval letter is lack of such crucial information which is required. (3) table 2&3, the laboratory test results on admission should be presented as "median (IQR)" (4) footnote for table 3, "with three signs = GGO, consolidation and linear opacity", please fix the typos. (5) Table 3 can be deleted, a description of significant results in the content should be sufficient. (6) Fig 4, using arrows in the images to indicate described lesions in the legend will be helpful. (7) in discussion, what will be potential long-term pulmonary sequelae in COVID-19? Authors should cite more available evidence regarding long-term pulmonary sequelae in SARS and MERS patients to support their prediction, particularly lung fibrosis. (8) clarify "characteristics unmatched with OP pattern" in the method. [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 ******** 2. 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: Overall a good and well written manuscript. Please grammar check the manuscript. Title:Ok Abstarct:Ok Introduction and Aim: Ok Materials and methods : Were there any cases of mixed infections? Results:Ok Discussion: Ok Conclusion: Ok Tabels : Ok Figures:Please add few more CT images showing evolution of the findings. ****** 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 [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.0240347.r001
Revision 1
14 Sep 2020 Author Response Editor Comments: (1) the format of number, such as "79(74.5%) patients were non-severe and 103(97.2%)", a space should be inserted between "number" and "(..%)". Please change throughout the entire manuscript. Re to ED1: We are so appreciated for your warm help and valuable comments in reviewing our paper that indeed make us think deeply and improve our work. According to your suggestion, we have revised the numerical format of the entire manuscript. In addition, we have checked the whole text and revised the related details. (2) IRB protocol of XJTU1AF2020LSK-011 is a multiple-center single IRB? This needs to be confirmed and clarified in the content since patients from multiple hospitals being involved. However, the attached copy of IRB approval letter is lack of such crucial information which is required. Re to ED2: Thanks for your comments. This multicenter study was launched by the institution of the first author, and approved by all the multicenter institutions. For ethic issue, IRB protocol of XJTU1AF2020LSK-011 is a multiple-center and we have clarified this in the attached copy of IRB approval letter. (3) table 2&3, the on admission should be presented as "median (IQR)" Re to ED3: Thanks for your comments. At the initial of this multicenter study, we used a general protocol for data collection. The categorized format of laboratory test (increase, decrease or within the normal range) was utilized. Given this, the data with count (percentage) was calculated and reported in the results. (4) footnote for table 3, "with three signs = GGO, consolidation and linear opacity", please fix the typos. Re to ED4: Thanks for your comments. The typos of “with three signs = GGO, consolidation and linear opacity” have been revised in the paper. (5) Table 3 can be deleted, a description of significant results in the content should be sufficient. Re to ED5: Thanks for your suggestion. The related contents have been revised as “Significant demographics and laboratory test difference between complete absorption and residuals groups were found in age (34.9 ± 9.0 vs. 47.9 ± 13.7, P = 0.001), elevated C-reactive protein (31.6% vs. 70.5%, P = 0.009) and neutrophil percentage (10.0% vs. 37.0%, P = 0.020)”. And Table 3 was placed in the supplementary materials to provide a more detailed reference to readers. (6) Fig 4, using arrows in the images to indicate described lesions in the legend will be helpful. Re to ED6: Thanks for your suggestion. The arrows to indicate described lesions in the legend have been added in the figure 4. (7) in discussion, what will be potential long-term pulmonary sequelae in COVID-19? Authors should cite more available evidence regarding long-term pulmonary sequelae in SARS and MERS patients to support their prediction, particularly lung fibrosis. Re to ED7: Thanks for your comments. Recent studies investigated pulmonary sequelae of COVID-19 and discovered that a substantial number of patients had radiological abnormalities after discharge, including GGO and pulmonary fibrosis [1, 2]. However, the impact of long-term pulmonary sequelae of COVID-19 on lung function remains to be validated in future. Previous follow-up chest radiographs obtained from the patients with MERS-CoV and SARS-CoV showed a substantial portion (around 30%) chest radiographic abnormalities, which were characterized by the presence of pulmonary fibrosis, GGO, and pleural thickening [3-5]. Note that radiological sequelae from SARS and MERS partially accounted for the repaired lung function, such as complaint of limitation in general physical function and/or shortness of breath in the early rehabilitation phase. Differently, slighter residuals mainly presenting with linear opacities was found in OP pattern of COVID-19 and the proportion of pulmonary residuals after discharge was lower in our cohort, which may be linked to our cohort coming from non-epidemic areas outside Wuhan and most patients were non-severe. We have thoroughly discussed this in discussion part. (8) clarify "characteristics unmatched with OP pattern" in the method. Re to ED8: Thanks for your precious comments. Referring to prior articles of H1N1 pneumonia [6], CT findings may simulate organizing pneumonia (OP), bronchopneumonia, or acute interstitial pneumonia (AIP) pattern. In detail, the lesions were considered to belong to OP pattern when lung abnormalities showed areas of consolidation or GGO showing lower lung zone predominance and being distributed along the subpleural lungs or bronchovascular bundles. They were regarded to belong to AIP pattern when the abnormalities demonstrated areas of consolidation with or without GGO showing patchy and extensive distribution without zonal predominance. And they were presumed to belong to bronchopneumonia pattern when the abnormalities had combination of consolidation, GGO, small centrilobular nodules and bronchial or bronchiolar wall thickening. We have clarified the characteristics unmatched with OP pattern as “The pulmonary lesions were considered to unmatched with OP pattern: (1) extensive GGO and/or consolidation diffusely in both lungs; (2) total CT score greater than 10; (3) combined consolidation and GGO with bronchial or bronchiolar wall thickening. Patients which were with unmatched with OP pattern or unqualified CT images were excluded” in the materials and methods part. References 1. Zhao Y, Shang Y, Song W, Li Q, Xie H, Xu Q, et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine 2020:100463. 2. You J, Zhang L, Ni-jia-ti M, Zhang J, Hu F, Chen L, et al. Anormal pulmonary function and residual CT abnormalities in rehabilitating COVID-19 patients after discharge. J Infect. 2020, 16:32. doi:10.1016/j.jinf.2020.06.003. 3. Xie L, Liu Y, Fan B, Xiao Y, Tian Q, Chen L, et al. Dynamic changes of serum SARS-coronavirus IgG, pulmonary function and radiography in patients recovering from SARS after hospital discharge. Respir Res. 2005 Jan 8;6(1):5. 4. Chan KS, Zheng JP, Mok YW, Li YM, Liu Y, Chu C, et al. SARS: prognosis, outcome, and sequelae. Respirology. 2003 Nov;8 Suppl (Suppl 1):S36-40. 5. Das K, Lee E, Singh R, Enani M, Dossari K, Gorkom K, et al. Follow-up chest radiographic findings in patients with MERS-CoV after recovery. Indian J Radiol Imaging. 2017;27: 342. doi:10.4103/ijri.IJRI_469_16. 6. Kang H, Lee KS, Jeong YJ, Lee HY, Kim K Il, Nam KJ. Computed tomography findings of influenza a (H1N1) pneumonia in adults: Pattern analysis and prognostic comparisons. J Comput Assist Tomogr. 2012. doi:10.1097/RCT.0b013e31825588e6. Reviewer #1’s Comments: (1) Materials and methods: Were there any cases of mixed infections? Re to RE1: We appreciate very much for your kindly help and valuable comments in reviewing our paper that indeed make us think deeply and improve our work. Recent studies have reported co-infections in people with COVID-19. According to recent paper [1], Lansbury et al. conducted a systematic review and meta-analysis of patients with coinfections in COVID-19 and they found 7% of hospitalized COVID-19 patients had a bacterial co-infection and 3% had viral co-infection. The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae while the commonest virus were Respiratory Syncytial Virus and influenza A. However, in our cohort, no cases had mixed infections, this may be because that most of our patients were from non-epidemic areas outside Wuhan, and most patients were non-severe. We have clarified this in results part. References 1. Lansbury L, Lim B, Baskaran V, Lim WS. Co-infections in people with COVID-19: a systematic review and meta-analysis. J Infect. 2020;81: 266–275. doi:https://doi.org/10.1016/j.jinf.2020.05.046. (2) Figures: Please add few more CT images showing evolution of the findings. Re to RE1: Thanks for your suggestion. We have added other CT images as figure 5 to present evolution of findings. This was a 55-year-old male who had fever for 6 days and discharged 1 month later. CT obtained on day 6 after admission showed focal GGO on bilateral lower lobes. On day 10 CT showed progressed mixed consolidation and on day 18 CT showed mixed consolidation and linear opacities. The day before discharge the patient performed CT examination and found that lesions were partially absorbed and there were residual consolidation and linear opacities in bilateral lower lobes. Response to Editor’s Comments 1) Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study. Re to ED1: Thanks for your comments. We have revised the current ethics statement and included the full name of the ethics committee/institutional review board(s) as following: “ This multicenter study was launched by the First Affiliated Hospital of Xi’an Jiaotong University, and approved by all the multicenter institutions, including the First Affiliated Hospital of Xi’an Jiaotong University, the Eighth Hospital of Xi’an, Xi’an Chest Hospital, Ankang Center Hospital, Wuhan No.9 Hospital, Hanzhong Center Hospital, Baoji Center Hospital. For ethic issue, IRB protocol of XJTU1AF2020LSK-011 is multiple-center.” The above statement has been added at the beginning of the Methods section of our manuscript file. 2) We note that your Data Availability Statement reads, "Since this is multi-center cooperation data, we do not have full access to it, so we can only share part of the data from our hospital. All relevant data are within the manuscript and its Supporting Information files." Could you please clarify whether "Supporting information.zip" contains your full Minimal Data Set, or whether the data from additional centers/hospitals is necessary for replication? Re to ED2: Thanks for your suggestion. Due to the data privacy protection policy, we have tried our best to communicate with multi-center ethics review board and sorted minimal data set to support our conclusion. This minimal data set was from multiple hospitals and was able to replicate our conclusions. Attachments Attachment Submitted filename: Response to Editor-0905.docx https://doi.org/10.1371/journal.pone.0240347.r002
25 Sep 2020 Decision Letter - Wenbin Tan, Editor Organizing Pneumonia of COVID-19: Time-dependent Evolution and Outcome in CT Findings PONE-D-20-17536R1 Dear Dr. Yang, 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, Wenbin Tan Academic Editor PLOS ONE Additional Editor Comments: The revised manuscript has addressed the comments well. This is a very important report to show the potential sequelae in discharged COVID-19 patients, though 3-month follow-up time is bit short as a limitation. I would look forward to a year or even longer time follow-up study from the same group in future. https://doi.org/10.1371/journal.pone.0240347.r003
Formally Accepted
29 Sep 2020 Acceptance Letter - Wenbin Tan, Editor PONE-D-20-17536R1 Organizing Pneumonia of COVID-19: Time-dependent Evolution and Outcome in CT Findings Dear Dr. Yang: 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. Wenbin Tan Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0240347.r004

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