Physiological respiratory parameters in pre-hospital patients with suspected COVID-19: A prospective cohort study

Johan Mälberg; Nermin Hadziosmanovic; David Smekal

doi:10.1371/journal.pone.0257018

Peer Review History

Original SubmissionMay 10, 2021
26 Jul 2021 Decision Letter - Chiara Lazzeri, Editor PONE-D-21-15446 Respiratory mechanics in pre-hospital patients with suspected covid-19: A prospective cohort study PLOS ONE Dear Dr. Mälberg, 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. This a well conducted investigation, dealing with a hot topic. We suggest the Authors to better discuss the clinical significance of capnography in this specific clinical setting. A paragraph describing the potential clinical impact of the present results should be added. Please submit your revised manuscript by Sep 09 2021 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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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. 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(Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The authors present the results of a prospective cohort study in the pre-hospital setting focusing on physiopathological respiratory parameters in patients with suspected COVID-19. They mainly found an association between COVID-19 diagnosis and/or need for hospitalization from one part and rapid shallow breathing and negative inspiratory pressure from another part. They also report an association between physiological dead-space and hospital admission. The authors should be congratulated for such a difficult to achieve clinical study. I have some comments aiming to clarify some issues and to help do discuss some results. Major comments 1. The authors should be congratulated for the study, permitting to appreciate in part both gas exchanges and volume/pressure parameters. In this way, since severity of COVID-19 is predominantly linked to respiratory failure, it could be interesting to display and discuss more deeply oxygen saturation results, not only for description of the included population but also for appreciating the respective interests of SaO2, capnography and spirometry results for prediction of COVID-19 diagnosis and severity. 2. The capnography results (link to COVID-19 severity) could be discussed in light of the hypothesis of large amounts of alveolar dead-space in relation to lung microvascular endothelialitis and microthrombosis. These aspects are discussed in the following reference: Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study. Ann Intensive Care. 2020 Jul 16;10(1):95. doi: 10.1186/s13613-020-00716-1. More generally, there are various arguments for such a hypothesis (see as an example: COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects. Angiogenesis. 2021 Jun 28:1-34. doi: 10.1007/s10456-021-09805-6.). Minor comments 1. The tittle could be modified to “Physiological respiratory parameters in pre-hospital patients: …”. Indeed, respiratory mechanics typically do not include physiological dead-space measurements and is best appreciated by both pressure and volume measurements, including in spontaneously breathing patients esophageal pressure measurements. The same apply for Table legends, etc. 2. The interest of Figure 1 seems to me debatable. 3. Ref. 14 refers to a 6ml/kg PBW, not 7. 4. Ref 25 doesn’t refer to a COVID-19 study. ****** 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. 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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.0257018.r001
Revision 1
17 Aug 2021 Author Response Response to reviewers The authors would like to thank the editor and reviewer for their hard work and valuable suggestions for improvement regarding our manuscript. Please see the answers to each individual comment below. We hope that you will find the revised manuscript suitable for publication in PLOS ONE. Sincerely Johan Mälberg Editor’s comments: This a well conducted investigation, dealing with a hot topic. We suggest the Authors to better discuss the clinical significance of capnography in this specific clinical setting. A paragraph describing the potential clinical impact of the present results should be added Author response: We have discussed the clinical significance of capnograhy in greater detail, line 279-285. We have added two paragraphs discussing the potential clinical impact of the study’s findings, line 318-329. Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. 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 Author response: We have updated the manuscript in accordance with the submission guidelines and style requirements. File names have been revised in accordance to the guidelines. Please see the revised manuscript with tracked changes for all individual changes. 2. During your revisions, please note that a simple title correction is required: please correct "covid-19" to "COVID-19". Please ensure this is updated in the manuscript file and the online submission information. Author response: We have corrected covid-19 to COVID-19. 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. Author response: We have updated the cover letter with information regarding the limits in our ethical approval that prohibits us from sharing our full minimal data set. In order to share as much of our underlying data as possible, we have blocked certain information in our minimal data set to prevent individual participants from being identifiable. This was done after consulting the Swedish Ethical Review Authority in order comply with our ethical approval, but also with Swedish law and the EU’s general Data Protection Regulation. We have added the minimal data set as supporting information and updated our data availability section to reflect this. The previous data availability statement was due to a misunderstanding on the corresponding authors’ part. We apologize for the mistake. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 4. We note that Figure 1 in your submission contain copyrighted images. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For more information, see our copyright guidelines: http://journals.plos.org/plosone/s/licenses-and-copyright. We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission: a. You may seek permission from the original copyright holder of Figure 1 to publish the content specifically under the CC BY 4.0 license. We recommend that you contact the original copyright holder with the Content Permission Form (http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text: “I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.” Please upload the completed Content Permission Form or other proof of granted permissions as an "Other" file with your submission. In the figure caption of the copyrighted figure, please include the following text: “Reprinted from [ref] under a CC BY license, with permission from [name of publisher], original copyright [original copyright year].” b. If you are unable to obtain permission from the original copyright holder to publish these figures under the CC BY 4.0 license or if the copyright holder’s requirements are incompatible with the CC BY 4.0 license, please either i) remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only. Author response: Figure 1 was a picture taken by the corresponding author. It has been removed in accordance with the suggestion from reviewer 1. The remaining figures have been renamed accordingly. Review comments to authors Reviewer #1: The authors present the results of a prospective cohort study in the pre-hospital setting focusing on physiopathological respiratory parameters in patients with suspected COVID-19. They mainly found an association between COVID-19 diagnosis and/or need for hospitalization from one part and rapid shallow breathing and negative inspiratory pressure from another part. They also report an association between physiological dead-space and hospital admission. The authors should be congratulated for such a difficult to achieve clinical study. I have some comments aiming to clarify some issues and to help do discuss some results. Author response: We would like to thank the reviewer for the kind words and the valuable comments. Major comments 1. The authors should be congratulated for the study, permitting to appreciate in part both gas exchanges and volume/pressure parameters. In this way, since severity of COVID-19 is predominantly linked to respiratory failure, it could be interesting to display and discuss more deeply oxygen saturation results, not only for description of the included population but also for appreciating the respective interests of SaO2, capnography and spirometry results for prediction of COVID-19 diagnosis and severity. Author response: We have added a discussion concerning our SaO2 findings, line 256-266. We agree that SaO2 is an interesting parameter with regards to COVID-19 even though we did not find any significant differences with regard to the SaO2 levels in our study. 2. The capnography results (link to COVID-19 severity) could be discussed in light of the hypothesis of large amounts of alveolar dead-space in relation to lung microvascular endothelialitis and microthrombosis. These aspects are discussed in the following reference: Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study. Ann Intensive Care. 2020 Jul 16;10(1):95. doi: 10.1186/s13613-020-00716-1. More generally, there are various arguments for such a hypothesis (see as an example: COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects. Angiogenesis. 2021 Jun 28:1-34. doi: 10.1007/s10456-021-09805-6.). Author response: We have added a discussion of the capnography results and dead space and added the first mentioned article as a reference, line 279-285. We find this study’s hypotheses very interesting in combination with our findings, which could implicate that the damage to the lungs is detectable early on with our method of measuring the physiological respiratory parameters. Minor comments 1. The tittle could be modified to “Physiological respiratory parameters in pre-hospital patients: …”. Indeed, respiratory mechanics typically do not include physiological dead-space measurements and is best appreciated by both pressure and volume measurements, including in spontaneously breathing patients esophageal pressure measurements. The same apply for Table legends, etc. Author response: We agree with the reviewer and have changed the title and the term used in the manuscript to physiological respiratory parameters. 2. The interest of Figure 1 seems to me debatable. Author response: We agree and have removed the figure. 3. Ref. 14 refers to a 6ml/kg PBW, not 7. Author response: The reviewer is correct. Most sources cite the normal value of tidal ventilation in healthy adults as 6-8 ml/kg. This should have been made clearer. We have changed reference 14 to one that in detail describes the basis of 7 ml/kg and how it came to be. 4. Ref 25 doesn’t refer to a COVID-19 study. Author response: We agree that the way the references were mentioned it was not clear that reference 25 did not concern COVID-19. We have changed this to make it clearer. Even though the article does not concern COVID-19, we think it adds value as it shows that changes in dead space occur in ARDS, which severe COVID-19 can cause Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0257018.r002
23 Aug 2021 Decision Letter - Chiara Lazzeri, Editor Physiological respiratory parameters in pre-hospital patients with suspected COVID-19: A prospective cohort study PONE-D-21-15446R1 Dear Dr. Mälberg, 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.0257018.r003
Formally Accepted
26 Aug 2021 Acceptance Letter - Chiara Lazzeri, Editor PONE-D-21-15446R1 Physiological respiratory parameters in pre-hospital patients with suspected COVID-19: A prospective cohort study Dear Dr. Mälberg: 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.0257018.r004

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