PONE-D-20-25960

Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of Coronavirus Disease-2019 (Covid-19) from China

PLOS ONE

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[This study was funded by the National Natural Science Foundation (81972146), the

Department of Science and Technology of Sichuan Province (20YYJC3320), China

Postdoctoral Science Foundation (2020M673251), Health Commission of Sichuan

Province (20PJ034), and West China Hospital of Sichuan University (HX-2019-nCoV-

011 to Chengqi He, and 2019HXBH058 to Siyi Zhu). The funders played no role in the design, conduct, or reporting of this study.]

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Additional Editor Comments (if provided):

Reviewers have taken an interest in the study and found it to be valuable work in several respects. However, several limitations of the manuscript still do not allow a final decision to be made as to whether the study should be published. I suggest that the authors take advantage of the suggestions of the two reviewers to improve the quality of the manuscript and make it suitable for publication.

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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: Yes

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

Reviewer #1: I Don't Know

Reviewer #2: 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.

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: Overall, I think that this is a useful study and there have been few publications to date that have considered the post-acute aspects of COVID-19. I do feel that the study itself has several limitations, however, which are largely highlighted by the authors. My main issue is the lack of data regarding functional status prior to hospitalisation. The authors have used co-morbidity as a surrogate marker for this but given that hypertension is included as such, I do not think that there would necessarily be a strong correlation with functional dependence so I am not sure how valid it really is to use this. I would presume that the majority of patients admitted to hospital would have some background information gathered on their level of dependency/frailty as it usually forms a standard part of the history taking. However, given that this was a retrospective study and many of the patients were from Hubei province and admitted at the height of the pandemic, these details may not have been recorded and I also recognise that an incomplete data set may not add a huge amount to the interpretation of the findings. It is also interesting that a single recorded respiratory rate of above 30 is considered in isolation to be a marker of severe disease given that there could be many factors that could contribute to this (co-existent COPD or other chronic lung/heart condition/metabolic derangement/inaccurate documentation).

Although self-reported questionnaires may be less accurate than those recorded by the investigators, given that the findings are highly predictable, I suspect that overall would make little difference to the outcomes. I think that the study would be greatly enhanced by reassessing the same cohort at 3 months and it could be argued that this will provide more meaningful information regarding the longer term needs of those who have had COVID-19. However, given that early rehab/intervention programmes have long been established as key for effective rehabilitation, this study highlights the burden of disability at discharge and thus makes an important point regarding resource allocation and need for investment in post-acute COVID services (which in my experience has been somewhat overlooked).

There are a few typos (line 152 appears to be missing a word) and the introduction is slightly ‘media-like’ but overall I think it is reasonably well written and gets the points across well, in particular the limitations

Reviewer #2: This ms presents findings of analyses of data from 424 Covid-19 survivors in 8 provinces of China that make a strong case that those with more severe disease have increased disability and anxiety at discharge from the hospital. There are several areas of concern that the authors need to address before a final decision can be made regarding publication.

1. While the results in the tables and Figures convey findings that are clearly statistically significant – e.g., Risk Ratios and 95%CIs for effects of Disease Severity, Ethnicity and Province on Anxiety in Figure 2 that do not overlap with 1 – it would help the reader appreciate these effects if the authors included P-values in the tables and text – e.g., “Having severe Covid-19 was the strongest risk factor for probable clinically relevant anxiety (P<0.00xx).” It would also be helpful to provide P-values for the age x disease severity effects reported in Table 2 and illustrated in Figure 3.

2. How are the three outcomes of IADL, ADL dependence and Anxiety correlated with each other? It is likely that those with more IADL and/or ADL dependence with have higher Anxiety levels, and it will be good to document and report whether that is the case. There is evidence in the literature that these factors are correlated (e.g., Clancy F, O'Connor DB, Prestwich A. Do Worry and Brooding Predict Health Behaviors? A Daily Diary Investigation. Int J Behav Med. 2020 Oct;27(5):591-601).

3. Given that the three outcomes are likely to be correlated, it could also be informative if the authors performed additional analyses to determine whether, e.g., the effect of disease severity to increase IADL is mediated by the effect of disease severity to increase Anxiety (or vice versa). This could be accomplished by using structural equation modeling to determine whether there is a significant indirect path – i.e., increased disease severity � increased Anxiety � increased IADL.

4. In addition to Anxiety it would have also been informative if the authors had included a measure of depression – e.g., Zung Self-Rating Depression scale – to determine whether disease severity was also associated with the psychological disorder. They cited evidence (ref 31) showing that depression levels are increased in Chinese health Care Workers exposed to coronavirus disease, so it is likely that depression levels are also elevated in the patients with severe disease in the current study.

5. The authors note the important implication of their findings that early psychological/rehabilitation interventions could be useful in improving mental and physical health in Covid-19 survivors. There is evidence that training in cognitive behavioral stress management skills has been effective in reducing depression and anxiety in male cardiac surgery patients in Singapore (Bishop GD, Kaur D, Tan VL, Chua YL, Liew SM, Mak KH. Effects of a psychosocial skills training workshop on psychophysiological and psychosocial risk in patients undergoing coronary artery bypass grafting. Am Heart J. 2005 Sep;150(3):602-9) and Chinese medical students (Li C, Chu F, Wang H, Wang XP. Efficacy of Williams LifeSkills training for improving psychological health: a pilot comparison study of Chinese medical students. Asia Pac Psychiatry. 2014 Jun;6(2):161-9).

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Reviewer #1: No

Reviewer #2: No

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Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of Coronavirus Disease-2019 (Covid-19) from China

PONE-D-20-25960R1

Dear Dr. Reinhardt,

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.

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Stefano Federici, Ph.D.

Academic Editor

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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 #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 #2: Yes

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

Reviewer #2: 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.

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 #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 #2: The authors have responded well to my concerns. There's only a minor problem they need to address -- i.e., net to insert P<0.001 next to "Pre-existing comorbidity" in Table 1

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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 #2: No