PONE-D-21-37749Impact of covid-19 on long-term oxygen therapy 2020: a nationwide study in SwedenPLOS ONE

Dear Dr. Josefin Sundh,

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 study reports a lower incidence of LTOT in Sweden between March and December 2020, in comparison to the incidence of LTOT in the same months during 2015-2019. The main hypothesis is that the overall incidence of LTOT had increased due to covid-19. Authors estimated that Covid-19 caused one fifth of all new LTOT during the pandemic in 2020. Despite having a solid source of data represented by the National Registry of Respiratory Failure, reviewers arise major concers, which need to be better discussed and explored.Moreover, I questioned if patients with respiratory comorbidity (mainly with COPD) that died from COVID-19 and the reduction of follow-up visits expecially during the first wave could represent another reason of lower new OTLT during 2020.   Please submit your revised manuscript by Mar 24 2022 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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Additional Editor Comments:

This study reports a lower incidence of LTOT in Sweden between March and December 2020, in comparison to the incidence of LTOT in the same months during 2015-2019. The main hypothesis is that the overall incidence of LTOT had increased due to covid-19. Authors estimated that Covid-19 caused one fifth of all new LTOT during the pandemic in 2020. Despite having a solid source of data represented by the National Registry of Respiratory Failure, reviewers arise major concers, which need to be better discussed and explored. Moreover, I questioned if patients with respiratory comorbidity (mainly with COPD) that died from COVID-19 could represent another reason of lower new OTLT during 2020.

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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: Partly

Reviewer #2: Yes

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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: Yes

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: The authors present an interesting analysis of LTOT dispensings in Sweden in 2020. The 2020 numbers were lower than those seen in the previous 5 years.

Major comments:

While I believe this paper accurately describes LTOT dispensings in Sweden in 2020- I also think that it may not fully be capturing the affect of of COVID. In Figure 1, COVID cases did not surge in Sweden until late in 2020 ( and most of 2021). Thus- I suspect this same study extended into 2021 might look different.

Are data available on a metric such as COPD hospitalizations over this time period? The US saw a drop in these during 2020 ( probably related to social distancing). I suspect this may have also been a factor in places like Sweden.

Reviewer #2: General comment

The main aims of this study were to explore the incidence of LTOT due to covid-19 as well as the total incidence of LTOT in Sweden between March and December 2020, in comparison to the incidence of LTOT in the same months during 2015-2019. The main hypothesis is that the overall incidence of LTOT had increased due to covid-19. The major results were that the total number of patients starting LTOT did not increase and no significant differences in patient characteristics or underlying causes of hypoxemia were found between patients starting LTOT during 2020 compared to 2015-2019. Authors estimated that Covid-19 caused one fifth of all LTOT starts during the pandemic in 2020. Despite having a solid source of data represented by the National Registry of Respiratory Failure, the paper has good purposes, but has some weak points which need to be better discussed and explored.

Major corrections

1) Introduction: After two years of the pandemic, numerous studies have concluded that during the follow-up Lung volumes, DLCO, chest radiographic abnormalities and respiratory symptoms tend to normalize or improve 1 year after hospitalization for COVID-19 in most patients. Thus, it is difficult to hypothesize that Covid-19 is directly responsible for chronic respiratory failure (Truffaut et al. Respir Res 2021; 22:29 https://doi.org/10.1186/s12931-021-01625-y) (Balbi M et al. Eur J Radiol 2021; 138 https://doi.org/10.1016/j.ejrad.2021.109676). Please, in the light of these findings, define better the background and aim of the study in the background.

2) The choice of the reference period is questionable. In the six months between October 2020 and March 2021, the Sweden saw 657 ,309 positive cases in comparison to just under 93 ,000 cases by 1 October 2020 since the onset of pandemic. (Paterlini M, BMJ 2021; 375 doi: https://doi.org/10.1136/bmj.n3081). The authors described in Figure 1 the higher incidence of cases in the second and third pandemic waves. It is reasonable to believe, as partly discussed by the authors, that the initiation of LTOT is mainly attributable to underlying pre-existing chronic disease, since Covid-19 may have a more temporary need of oxygen therapy. It is not clear, in fact, the prescribing criteria of LTOT in Covid-19 patients, considering that the estimate of patients with Covid-19 is obtained only from local records. Do Authors think that an extension of the enrollment period could provide more robust evidence regarding hypothetical prescribing changes related to the pandemic?

3) Methods: ‘Patients on palliative oxygen or oxygen used only at exertion was not included’. Do authors think that this choice may have excluded those patients suffering from sequelae of severe forms of Covid-19 related pneumonia (i.e. DNR patients or patients requiring a rehabilitation period)?

4) It would be interesting to have more detailed clinical data on Covid-19 patients who started LTOT. Were patients with severe pneumonia or sequelae treated in ICU? How many patients were hospitalized? Did patients have any concomitant chronic diseases? Did any patient eventually discontinue the LTOT after a rehabilitation period or 1-year post-discharge?

5) Do you think it is possible to identify patients who have required prolonged weaning from ventilation or tracheostomy for Covid-19 pneumonia? This subgroup of hospitalized patients may have been prescribed by OTLT. Expecting a higher hospitalization rate during the second and third Covid-19 waves, it is reasonable to assume a higher number of patients eligible for OTLT by extending the referral / enrollment period.

Minor corrections

1) Please, indicate the estimate updated date of the sentence ‘Up to date, the global number of people diagnosed with covid-19 is over 180 million, and almost 4 million have died due to the disease’.

2) Please specify units of measurement in table and graphs.

3) Please verify in the text %, use the same style: i.e. Number and ‘%’ without space character (i.e. 20%)

4) Please verify in the text, use the same style for thousands separator, authors used ‘,’ and space characters (i.e. 234 665 or 234,665)

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Reviewer #1: Yes: David Mannino

Reviewer #2: No

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Impact of covid-19 on long-term oxygen therapy 2020: a nationwide study in Sweden

PONE-D-21-37749R1

Dear Dr. Josefin Sundh,

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,

Manlio Milanese

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Comment to Reviewers were adequately addressed. The manuscript is now imporved and suitable for publication on PlosOne.

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: My prior comments have been addressed. I would like to see this replicated when 2021 data becomes available- as the findings may differ!

Reviewer #2: The manuscript contains adequate insights and the authors have answered exhaustively to the questions and requests for revision.

Minor revision

Please provide to use in the paper the same acronym for Covid-19

Line 75: correct it into It

Line 168: correct 10/100 000 into 10/100,000

Line 170: correct 100 000 into 100.000

Please verify in the paper, tables and footnotes to write thousands numbers in the same style

Line 202: correct one.year into one-year

Line 245: please consider to write in full and cite BTS guidelines in references

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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: David Mannino

Reviewer #2: No