PONE-D-22-26441Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: prospective cohort studyPLOS ONE

Dear Dr. Ribeiro Carvalho,

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Academic Editor

PLOS ONE

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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: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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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

Reviewer #2: Yes

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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: No

Reviewer #2: Yes

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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: Title: Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: prospective cohort study

The authors conducted a prospective cohort study to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and to identify risk factors associated with chest CT lesion severity. The authors declared that the ML accurately detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity.

Comments:

1. In Abstract, Method, the follow-up period in the study was 6-12 months after hospital discharge. What is the reason for this prospective cohort study designed as an uncertain follow-up period? I suppose that the predictors for fibrotic change of CT checked at 6month may be different from those at 12month due to regression of image abnormalities in COVID-19 patients.

2. In Abstract, Method, the authors did not clearly define the primary outcome measure, CT severity, in this study.

3. In Abstract, Method, the authors did not mention the time point after discharge for performing chest CT and pulmonary function test.

4. In Abstract, Results, that authors mentioned that “An association between the CT feature severity and an impaired PFTs was not found.” However, in Table 3, there were statistical significances in some variables.

5. In Abstract, Conclusion, the authors mentioned “….. were risk factors to the development of severe CT lesion after discharge.”. How to define the development of CT lesion after discharge or during hospitalization? Does it mean that CT lesion got progressive after discharge?

6. In Methods, 2.2 follow-up protocol, the enrolled criteria for performing chest CT and pulmonary function test were different from the description in Abstract. Please reedit it in Abstract.

7. In Results, Table 3, the follow-up duration in each group was not showed here.

8. In Results, Table 3, the authors mentioned that “patients with fibrotic-like changes were older, had a greater duration of ICU hospitalization and need of IMV, were more tracheostomized, had a lower FVC and VR, and a higher FEV1 and FEV1/FVC than those with mild/moderate lesion”. What is the meaning for mild/moderate lesion? The authors did not define what is the severity graded via the CT findings in ICU hospitalized COVID-19 patient in Methods. The authors did not provide CT extent scores, so how to define the severity in fibrotic group (Traction bronchiectasis, but no honeycombing in the study population) greater than non-fibrotic group (GGO,…).

9. In Results, Table 3, what is the reason that the authors did not include the signs of pulmonary involvement (enrolled criteria) as the variables for statistical analysis to test whether the signs of pulmonary involvement were the predictors of CT severity in the study patients?

10. In Discussion, 2nd paragraph, the authors mentioned that “This fact suggests that the respiratory mechanics is possibly more relevant than gas exchange in determining COVID-19 late respiratory alterations.” The authors should have more explanation for this statement. Dose the result of this study support this finding? Moreover, the reference 25 and the conclusion that “these data triggered the idea that possible interventions that improve lung mechanics would be important to reduce these dysfunctions.” Have any evidence to support it and how to do?

11. In Discussion, paragraph 2-4, the authors had discussions about parameters of lung mechanics (e.g., DLCO, TLC) in COVID-19. However, pulmonary function parameters were not the clinical predictors for CT severity in ICU hospitalized COVID 19. in additional to respiratory parameters, the authors can make a more comprehensive literature review to point out the predictors or factor associated with fibrotic-like changes in COVID 19 patients.

Reviewer #2: This manuscript was designed to investigate the long-term respiratory effect, including pulmonary function and chest CT findings, caused by the SARS-CoV-2 infection. Although this research was a prospective study, it seems that patients’ groups and medical record were divided and collected retrospectively. Therefore, the including and excluding criteria were not defined very clear. Several questions need to be answered.

1. Among patients enrolled for Chest CT scan (N=243), how many patients have chronic lung disease, including fibrotic

disease (reticulation), traction bronchiectasis, architectural distortion or malignancy? Were these patients divided into

fibrotic-like or without fibrotic-like change group?

2. Why did authors define reticulation on chest CT scan into the without fibrotic-like change group?

3. Sometimes, we can see “both” fibrotic-like changes and ground-glass opacities in a “single” chest CT scan. Furthermore,

it is very difficult to define this patient into with or without fibrotic-like group. How many patients in this study

encountered this issue and need to be resolved by consensus?

4. In this study, a machine learning model was developed to precited CT lesion severity. Did the authors validate this model

in other cohort to confirm its reproducibility?

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Reviewer #1: Yes: Hsin-Kuo Ko

Reviewer #2: No

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Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: prospective cohort study

PONE-D-22-26441R1

Dear Dr. Ribeiro Carvalho,

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.

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Kind regards,

Yu Ru Kou, PhD

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: All comments have been addressed

Reviewer #2: All comments have been addressed

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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

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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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

Reviewer #2: Yes

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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

Reviewer #2: Yes

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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: The authors have completely responded to my comments. No further issue about dual publication, research ethics or pulbilication ethics was found.

Reviewer #2: The manuscript was significantly improved after major revision and could be accepted in the present form.

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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: Yes: Hsin-Kuo Ko

Reviewer #2: No

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