Dear Dr. Grimaud,

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Kind regards,

Amir Nutman

Academic Editor

PLOS One

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Additional Editor Comments:

In addition to the reviewer's comments, I would like to highlight one editorial point for your revision. Given the context of mass transfers of critically ill patients during an infectious disease outbreak, the manuscript would benefit from a more explicit discussion of infection prevention (IPC) aspects. Specifically, please consider addressing issues such as transmission risk during transport, mitigation strategies implemented in each transport modality, and the implications of your findings for IPC planning in future large-scale transfers.(IPC) aspects. Specifically, please consider addressing issues such as transmission risk during transport, mitigation strategies implemented in each transport modality, and the implications of your findings for IPC planning in future large-scale transfers.(IPC) aspects. Specifically, please consider addressing issues such as transmission risk during transport, mitigation strategies implemented in each transport modality, and the implications of your findings for IPC planning in future large-scale transfers.(IPC) aspects. Specifically, please consider addressing issues such as transmission risk during transport, mitigation strategies implemented in each transport modality, and the implications of your findings for IPC planning in future large-scale transfers.

I look forward to receiving your revised submission.

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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?

Reviewer #1: Partly

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

Reviewer #1: No

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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.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: No

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4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

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Reviewer #1: Thank you for the opportunity to review this interesting manuscript.

I have two main reservations:

1. Length of stay in the destination ITU is used as an outcome measure to compare Train vs Air transport. However, the destinations between the two groups differ significantly (Table 2) and importantly. This is a key confounder and the most likely reason for the findings with regards to a shorter length of stay in patients transferred by train. Since they arrived in ICUs further away from the epicentre of the pandemic with likely more capacity and less requirement to discharge patients rapidly from ITU. The authors mention this but do not highlight it sufficiently (I disagree that "physical & care environments during transfer provide a more compelling explanation" for a median LOS of 6 days less in the train group). The manuscript should be adapted to make this key limitation more explicit. A geographical map summarising destinations for Train group vs Air group may be helpful to the reader. Average length of stay in ITU for the period in question at each destination Hospital would be very useful to assess the likely impact of destination ITU but appreciate this data may not be available.

2. 208 patients have been excluded from the initial 501 transfers. 171 due to unknown destination and 20 for unknown vectors. The authors also note "high proportion of missing data for some key parameters". The percentage of missing data for each parameter needs to be provided as a supplementary table - I am concerned that the SOFA score comparison presented (lines 207 to 210) may be misleading if a large volume of data points are missing. I am generally concerned with the large percentage of missing data and conclusions must be suitably cautious. The manuscript must make it explicit to the reader as to the uncertainty of any conclusions drawn from this data.

Other points for consideration

Line 82 - please include a comparison of what was available on trains in terms of procedures and tests vs air.

Paragraph from Line 85 to 90 should be in the methods section.

Line 89 "noradrenaline <1mg/h" - was this not mcg/kg/min? mg/h is not comparable between patients.

Line 110-111 helicopter vs fixed-wing are very different platforms. Even if data is incomplete would be useful to know the breakdown in the known data.

Line 135 "Catecholamine requirement" is used throughout the manuscript, does this exclude vasopressin? - would vasopressor/inotrope be preferable terminology?

Line 206-207 Only the air group is presented where as there is also a deterioration in the train group. Why is this not included? I would also ask for with-in group statistical analysis i.e paO2/Fio2 ratio before vs after in the train group & PaO2/Fio2 ratio before vs after in the air group as an assessment of statistically significant deterioration or not.

Line 284 "they had better nursing care" - this may be true but by what measure? At the very least this should be qualified with "may" - it should also be balanced with the more likely factor that they arrived in less pressured ICUs who were able to provide days of better ICU care thereby reducing the risk of nosocomial resp infections as an alternative (to my mind more likely) explanation for the findings.

Line 304-305 a cost analysis is performed in the conclusion. This should be moved to the discussion. Furthermore, I personally think this should be removed as a gross over-simplification of results based on generally poor data & extrapolating a cost saving is mis-leading.

Is there any information on the land transfer from hospital to airfield and airfield to hospital as this may be significant in some regions.

I thank the authors again for an interesting article with potential implications for any future pandemics/major incidents.

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what does this mean?). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes: Nick HaslamNick HaslamNick HaslamNick Haslam

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High-speed trains versus air transport vectors for mass transfers of critically ill patients: the TRANSCOV cohort study

PONE-D-25-62199R1

Dear Dr. Grimaud,

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,

Amir Nutman

Academic Editor

PLOS One

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions??>

Reviewer #1: Partly

**********

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.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

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5. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

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Reviewer #1: I would like to thank and congratulate the authors for addressing all previous comments and suggestions comprehensively. This is an important publication, highlighting an alternative transport method that is rarely used. The conclusions are now in line with the evidence presented with adequate exploration of key confounders. I think this will be of interest internationally to those involved in critical care transfer and emergency planning & response.

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what does this mean?). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). If published, this will include your full peer review and any attached files.). 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 For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our For information about this choice, including consent withdrawal, please see our Privacy Policy..-->

Reviewer #1: Yes: Nick HaslamNick HaslamNick HaslamNick Haslam

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