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. 2025 Aug 26;20(8):e0330938. doi: 10.1371/journal.pone.0330938

Mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID condition

Adrian Meule 1,*, Daniela Kroll 2,3, Martina Bönsch 3, Tessa Schneeberger 2,3, Inga Jarosch 2,3, Rainer Gloeckl 2,3, Ulrich Voderholzer 4,5,6,‡, Andreas R Koczulla 2,3,7,‡,✉
Editor: Kamal Sharma8
PMCID: PMC12380288  PMID: 40857338

Abstract

Background

Post-COVID condition is most commonly associated with physical symptoms such as dyspnea on exertion, difficulty in concentration, fatigue, and frailty but meta-analyses also document high rates of mental health problems such as anxiety disorders, depression, and post-traumatic stress disorder (PTSD).

Methods and findings

In the current study, 140 persons (66% female) receiving inpatient pulmonary rehabilitation treatment for post-COVID condition for an average of 27 days (SD = 11) completed self-report measures on mental and physical health at admission and discharge. At admission, 54%, 36%, 36%, and 14% screened positively for somatoform syndrome, generalized anxiety, depression, and PTSD, respectively. Higher pulmonary functioning related to higher self-reported physical functioning (but not to measures of mental health) at admission. Several self-reported indicators for mental and physical health improved from admission to discharge.

Conclusions

The current study corroborates findings about the high mental and physical burden of post-COVID condition. However, both mental and physical symptoms show partial improvement during a specialized inpatient pulmonary rehabilitation treatment.

Introduction

Coronavirus disease 2019 (COVID–19) is a viral infection that is most commonly associated with fever, cough, fatigue, and dyspnea [1,2]. Post-COVID condition refers to symptoms that continue or develop after three months after a COVID–19 infection and is most commonly associated with dyspnea on exertion, difficulty in concentration, fatigue, and frailty [3,4]. Meta-analyses also document high rates of mental health problems and estimate a prevalence of approximately 25% for anxiety disorders and depression and approximately 12% for post-traumatic stress disorder (PTSD; [4–6]), possibly resulting from symptoms causing severe disruption to daily life, lack of service and treatment options, and uncertainty of illness trajectories [7]. There are several treatment options for post-COVID condition but no uniform recommendations can be made [8,9]. Thus, there is an urgent need to evaluate the effects of existing treatment approaches on mental and physical health outcomes in patients with post-COVID condition.

In the current study, we examined mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID condition. Specifically, pulmonary functioning was assessed at admission with spirometry, blood gas analysis, and diffusion capacity for carbon monoxide, and patients completed questionnaires on mental and physical health at admission and discharge. There were three study aims: First, we examined the percentage of persons exceeding the cut-off scores across a large range of mental health problems to replicate and expand on prior findings [4–6]. Second, as it is currently unclear if and how physical and mental health impairments relate to each other in post-COVID condition, we tested whether pulmonary functioning at admission correlated with self-reported mental and physical health at admission. Third, as there is currently no “gold standard” treatment for post-COVID condition, we tested if and how self-reported mental and physical health changed during pulmonary rehabilitation treatment from admission to discharge.

Methods

Sample

This retrospective study of medical records using fully anonymized data did not require informed consent and was approved by the ethics committee at the University of Marburg (Marburg, Germany; reference no. 24–172 RS). Data of a consecutive sample of 140 persons who were infected with COVID–19 between 2020 and 2023 and who were admitted to inpatient pulmonary rehabilitation treatment for post-COVID condition at the Schön Klinik Berchtesgadener Land (Schönau am Königssee, Germany) between 16/01/2023 and 16/12/2023 were accessed on 19/06/2024 and analyzed. No additional inclusion or exclusion criteria were applied. Thus, time between the first COVID infection and admission to the hospital approximately ranged between 1–3 years (as the exact date of the first COVID infection could not be exactly determined retrospectively, no precise numbers can be reported here). Sample characteristics are displayed in Table 1. Treatment elements included diagnostic assessments, medical treatment, endurance and strength training, patient education, respiratory physiotherapy, relaxation techniques, occupational therapy, psychological support, and nutrition counseling [10].

Table 1. Sample characteristics.

Variables Descriptive statistics
Age (years) M = 50.8, SD = 13.8
Sex
 Female n/N = 92/140, 65.7%
 Male n/N = 48/140, 34.3%
Marital status
 Unmarried and single n/N = 15/140, 10.7%
 Unmarried and in a relationship n/N = 25/140, 17.9%
 Married or living with partner n/N = 67/140, 47.9%
 Divorced or separated or widowed and single n/N = 13/140, 9.3%
 Divorced or separated or widowed and in a relationship n/N = 20/140, 14.3%
Education
 Lower secondary education n/N = 27/135, 20.0%
 Middle secondary education n/N = 32/135, 23.7%
 Higher secondary education n/N = 28/135, 20.7%
 Tertiary education n/N = 48/135, 35.6%
Body mass index (kg/m²) M = 27.6, SD = 6.3
Forced expiratory volume (l/s) M = 2.8, SD = 0.9
Partial pressure of oxygen at rest (mmHg) M = 79.9, SD = 10.0
Diffusing capacity of the lungs for carbon monoxide (mmol/(min*kPa)) M = 7.9, SD = 3.7
Number of times infected with COVID–19
 Once n/N = 133/140, 95.0%
 Twice n/N = 6/140, 4.3%
 Three times n/N = 1/140, 0.7%
WHO Ordinal Scale for Clinical Improvement
 Ambulatory: limitation of activities n/N = 119/137, 86.9%
 Hospitalized: mild disease, no oxygen therapy n/N = 6/137, 4.4%
 Hospitalized: mild disease, oxygen by mask or nasal prongs n/N = 7/137, 5.1%
 Hospitalized: severe disease, non-invasive ventilation or high-flow oxygen n/N = 2/137, 1.5%
 Hospitalized: severe disease, intubation and mechanical ventilation n/N = 2/137, 1.5%
 Hospitalized: severe disease, ventilation and additional organ support n/N = 1/137, 0.7%
Mental disorders before first COVID–19 infection (self-reported)
 Depression n/N = 36/140, 25.7%
 Anxiety disorder n/N = 10/140, 7.1%
 Obsessive–compulsive disorder n/N = 2/140, 1.4%
 Post-traumatic stress disorder n/N = 11/140, 7.9%
 Eating disorder n/N = 0/140, 0.0%
 Personality disorder n/N = 2/140, 1.4%
 Schizophrenia n/N = 0/140, 0.0%
 Bipolar disorder n/N = 0/140, 0.0%
 Substance use disorder n/N = 1/140, 0.7%
 Chronic pain n/N = 9/140, 6.4%
 Other n/N = 7/140, 5.0%
Change in mental well-being since COVID–19 infection
 Improved n/N = 3/129, 2.3%
 No change n/N = 39/129, 30.2%
 Worsened n/N = 65/129, 50.4%
 Strongly worsened n/N = 22/129, 17.1%
Duration of inpatient pulmonary rehabilitation treatment (days) M = 26.9, SD = 11.0
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Measures

Pulmonary functioning. Pulmonary functioning was assessed at admission with spirometry (forced expiratory volume, FEV1), blood gas analysis (partial pressure of oxygen at rest, pO2), and diffusing capacity for carbon monoxide (DLCO).

Patient Health Questionnaire (PHQ). The PHQ is a self-report questionnaire for the assessment of mental disorders and associated symptoms in the past weeks [11] and patients completed the German version (PHQ–D; [12]) at admission and discharge. The PHQ includes different scales and response options and both categorical and continuous scores can be derived from item responses. Using the categorical scoring algorithms produces binary variables for the presence of somatoform syndrome (a pattern of multiple, recurrent, and frequently changing physical symptoms), depression, panic disorder, generalized anxiety, eating disorder, and alcohol use disorder. Using the continuous scoring instructions produces sum scores of items representing somatic symptoms severity (PHQ–15; for which internal consistency was ω = 0.81 at admission and ω = 0.87 at discharge), depressive symptoms severity (PHQ–9; for which internal consistency was ω = 0.84 at admission and ω = 0.89 at discharge), and stress (for which internal consistency was ω = 0.76 at admission and ω = 0.83 at discharge).

Primary Care PTSD screen (PC–PTSD). The PC–PTSD is a self-report questionnaire for the assessment of PTSD symptoms in the past month [13] and patients completed the German version [14] at admission and discharge. It has four items with dichotomous response options (0 = no, 1 = yes). Thus, sum scores can range between 0 and 4. Internal consistency was ω = 0.83 at admission and ω = 0.85 at discharge. A categorical score can also be derived using a cut-off score of 3, that is, there is an indication that a person might have PTSD when at least three items are answered with yes [13].

Short Form Health Survey (SF–36). The SF–36 is a self-report questionnaire for the assessment of mental and physical health in the past weeks [15,16] and patients completed the German version [17] at admission and discharge. It has 36 items with different response formats. All items are recoded such that mean scores of all subscales can range between 0 and 100, with higher values indicating better health. There are 8 subscales that represent physical functioning (for which internal consistency was ω = 0.93 at admission and ω = 0.94 at discharge), role limitations due to physical health (for which internal consistency was ω = 0.76 at admission and ω = 0.81 at discharge), role limitations due to emotional problems (for which internal consistency was ω = 0.88 at admission and ω = 0.95 at discharge), energy/fatigue (for which internal consistency was ω = 0.87 at admission and ω = 0.94 at discharge), emotional well-being (for which internal consistency was ω = 0.88 at admission and ω = 0.91 at discharge), social functioning (for which internal consistency was rsb = 0.84 at admission and rsb = 0.88 at discharge), pain (for which internal consistency was rsb = 0.91 at admission and rsb = 0.91 at discharge), and general health (for which internal consistency was ω = 0.74 at admission and ω = 0.72 at discharge).

Other information. Data on patients’ characteristics were taken from the clinical records at the hospital (e.g., age, sex, body height and weight, number and date of COVID–19 infections and impairment according to the WHO Ordinal Scale for Clinical Improvement, date of admission and discharge at the hospital). In addition, patients completed a self-made questionnaire that included questions on marital status and education as well as a question about how mental well-being has changed since the COVID–19 infection (response categories: strongly improved, improved, no change, worsened, strongly worsened) as part of the routine diagnostic assessment at the hospital.

Data analyses

Data were analyzed with R version 4.3.3 in RStudio version RStudio 2024.04.1. Descriptive statistics were computed with the package summarytools. Internal consistencies (McDonald’s ω for multi-item scales and split-half reliability with Spearman–Brown correction for two-item scales) of items used for composite scores were computed with the package psych. Correlations between continuous variables (Pearson’s coefficient) were computed with the package stats and between continuous and categorical variables (point-biserial coefficients) with the package ltm. To test changes in self-reported mental and physical health variables from admission to discharge, linear mixed models (for continuous variables) and generalized linear mixed models (for categorical variables) that included the fixed effect of time (admission vs. discharge) and a random intercept were computed with the package lme4. Effect sizes (Cohen’s d for continuous variables and Cohen’s g for categorical variables) were computed with the package effectsize. Because of the numerous inferential tests and large sample size, we considered effects as significant at p < 0.005, as has been recommended by Benjamin and colleagues [18] who argue that this alpha level “represents ‘substantial’ to ‘strong’ evidence according to conventional Bayes factor classifications” and “would reduce the false positive rate to levels we judge to be reasonable” (p. 7). The data and R code with which results can be reproduced are available at https://osf.io/byfzc.

Results

The majority of patients (67.5%) indicated that their mental well-being worsened or strongly worsened since the COVID–19 infection (Table 1). At admission, about half of the sample were screened positive for somatoform syndrome (54%), 36% for depression or generalized anxiety, respectively, 14% for PTSD, 9% for panic disorder, 7% for eating disorder, and none for alcohol use disorder (Table 2). Higher self-reported physical functioning related to higher forced expiratory volume and higher partial pressure of oxygen (Table 2). All other self-reported indicators of mental and physical health were unrelated to pulmonary functioning (Table 2). Somatic symptoms severity, depression, depressive symptoms severity, generalized anxiety, and stress decreased from admission to discharge with small-to-large effect sizes (Table 2). Physical functioning, energy/fatigue, and emotional well-being increased from admission to discharge with small-to-medium effect sizes (Table 2).

Table 2. Correlations between self-report measures of mental and physical health and pulmonary functioning indicators at admission as well as descriptive and inferential statistics for changes from admission to discharge.

Variables Correlations with pulmonary functioning Admission Discharge p Effect size
FEV1 pO2 DLCO
Patient Health Questionnaire
 Somatoform syndrome −0.12 −0.06 −0.03 n/N = 76/140, 54.3% n/N = 56/134, 41.2% 0.008 g = 0.25
 Somatic symptoms severity (PHQ–15) −0.17 −0.01 0.02 M = 13.7, SD = 5.2 M = 12.0, SD = 5.8 <0.001 d = 0.45
 Depression −0.15 0.05 0.04 n/N = 50/140, 35.7% n/N = 28/134, 20.9% 0.002 g = 0.29
 Depressive symptoms severity (PHQ–9) −0.12 0.08 0.04 M = 11.5, SD = 5.0 M = 9.0, SD = 5.5 <0.001 d = 0.60
 Panic disorder −0.19 −0.12 −0.18 n/N = 13/140, 9.3% n/N = 15/130, 11.5% 0.241 g = 0.12
 Generalized anxiety 0.01 −0.02 0.01 n/N = 51/140, 36.4% n/N = 35/133, 26.3% 0.004 g = 0.26
 Eating disorder 0.04 −0.06 0.09 n/N = 10/139, 7.2% n/N = 2/133, 1.5% 0.010 NA
 Alcohol use disorder NA NA NA n/N = 0/138, 0.0% n/N = 1/133, 0.8% NA NA
 Stress −0.03 0.03 −0.01 M = 6.9, SD = 3.8 M = 5.7, SD = 4.0 <0.001 d = 0.42
Primary Care PTSD Screen
 PTSD −0.02 0.06 −0.07 n/N = 20/140, 14.3% n/N = 18/132, 13.6% 0.719 g = 0.03
 PTSD symptoms −0.05 0.10 −0.004 M = 0.9, SD = 1.3 M = 0.9, SD = 1.3 0.879 d = 0.01
Short Form Health Survey
 Physical functioning 0.38* 0.27* 0.14 M = 47.3, SD = 24.0 M = 57.6, SD = 25.3 <0.001 d = 0.56
 Role limitations due to physical health 0.06 −0.05 −0.01 M = 15.2, SD = 26.8 M = 19.9, SD = 31.4 0.046 d = 0.17
 Role limitations due to emotional problems 0.17 0.12 0.02 M = 53.8, SD = 44.9 M = 57.6, SD = 47.2 0.403 d = 0.06
 Energy/fatigue −0.01 −0.09 −0.12 M = 26.6, SD = 16.9 M = 35.2, SD = 21.9 <0.001 d = 0.45
 Emotional well-being 0.08 −0.05 0.003 M = 57.3, SD = 20.2 M = 64.5, SD = 20.4 <0.001 d = 0.44
 Social functioning 0.11 −0.16 −0.09 M = 44.4, SD = 27.5 M = 50.6, SD = 29.5 0.005 d = 0.24
 Pain 0.10 0.06 −0.13 M = 48.7, SD = 29.2 M = 52.0, SD = 28.8 0.171 d = 0.11
 General health −0.004 −0.21 −0.002 M = 36.5, SD = 16.4 M = 40.1, SD = 16.6 0.006 d = 0.24
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Notes. FEV1 = Forced expiratory volume, pO2 = Partial pressure of oxygen, DLCO = Diffusing capacity of the lungs for carbon monoxide, PTSD = Post-Traumatic Stress Disorder, NA = Not available (values cannot be computed as one cell contains zero observations). Note that rules of thumb are 0.2 = small effect, 0.5 = medium effect, 0.8 = large effect for Cohen’s d and 0.05 = small effect, 0.15 = medium effect, 0.25 = large effect for Cohen’s g [31]. Correlations are Pearson’s coefficients for continuous variables and point-biserial coefficients when one of the variables is categorical.

*p < 0.005.

One of the reviewers asked whether treatment duration related to treatment outcome. Thus, we tested any time × length of stay interaction effects (see analysis code available here https://osf.io/byfzc), which were all p > 0.021, thus indicating that treatment duration did not relate to treatment outcome.

Discussion

Prevalence of mental health problems

In the current study, the majority of patients reported that their mental well-being worsened after the COVID–19 infection. In line with this, there were high rates of mental health problems. Specifically, 54% of the current sample screened positively for somatoform syndrome, 36% for generalized anxiety, 36% for depression, and 14% for PTSD.

The percentage of persons exceeding the somatoform syndrome cut-off score seems to be considerably higher than in other samples. For example, the prevalence of somatoform syndrome as assessed with the same instrument as in the current study (i.e., PHQ–15) was 25% in a sample of university students in Germany during the COVID–19 pandemic in 2021 [19] and, thus, less than half of the prevalence found in the current sample. Moreover, the mean somatic symptoms severity sum score was 14 in the current study and, thus, substantially higher than the score of 6 reported in sample of persons after a COVID–19 infection (with or without post-COVID condition; [20]).

The percentage of persons exceeding the generalized anxiety cut-off score also seems to be considerably higher than in other samples. For example, the prevalence of both panic disorder and other anxiety symptoms combined was 20% in the study by Holm-Hadulla and colleagues [19] and, thus, lower than the prevalence of generalized anxiety alone in the current sample.

The percentage of persons exceeding the depression cut-off score was not higher when compared to other samples. For example, the prevalence of depression as assessed with the same instrument as in the current study (i.e., the PHQ–9) was 42% in the study by Holm-Hadulla and colleagues [19] and, thus, slightly higher than the prevalence found in the current sample. However, the mean depressive symptoms severity sum score was 12 in the current study and, thus, higher than in other samples such as patients that presented at a post-COVID–19 clinic and in general internal medicine patients in the USA [21], a community sample of persons with or without a COVID–19 infection in the UK during the COVID–19 pandemic in 2021 [22], and patients with chronic obstructive pulmonary disease (COPD; [23]).

The percentage of persons exceeding the PTSD cut-off score was similar to a study reporting on patients recovering from COVID–19 infection in India [24]. However, when compared with studies that used the same instrument as in the current study (i.e., the PC–PTSD), it appears that the prevalence was actually lower than in other samples such as primary care patients [13], college students [25], and persons with post-COVID condition [26].

Relationships between pulmonary functioning and self-report measures

Higher physical functioning as measured with the SF–36 related to better pulmonary functioning as measured with FEV1 and pO2. In contrast, pulmonary functioning was unrelated to measures of mental health in the current study. This finding is in line with studies in patients with asthma and COPD that report that higher FEV1 primarily relates to higher scores on the SF–36 physical functioning subscale but not to scores on the SF–36 subscale emotional well-being [27,28]. Thus, it appears that while persons with post-COVID condition report high rates of mental health issues, these do not seem to be directly attributable to impaired pulmonary functioning.

Changes from admission to discharge

Somatic and depressive symptoms severity, generalized anxiety, and stress as assessed with the PHQ significantly decreased from admission to discharge with small-to-large effect sizes. In contrast, symptoms of panic disorder, eating disorders, and PTSD did not change from admission to discharge, suggesting that patients with post-COVID condition presenting with these symptoms require specialized psychotherapy in addition to pulmonary rehabilitation treatment. The largest improvements on the SF–36 were observed for physical functioning, energy/fatigue, and emotional well-being in the current study. In line with this, a recent study examining effects of hyperbaric oxygenation in outpatients with post-COVID condition reported comparable SF–36 scores across subscales at the beginning of treatment and also reported the largest improvements in physical functioning, energy/fatigue, and emotional well-being [9]. As inpatient treatment is more expensive than daypatient or outpatient treatment, future studies are needed that compare different treatment elements and treatment settings in terms of cost-benefit efficacy.

Limitations

Interpretation of results is limited to inpatients treated in Germany and may not translate to other countries with different healthcare systems. Moreover, indicators of mental and physical health were based on self-report questionnaires, which may potentially be biased (e.g., due to demand effects or social desirability, possibly leading to an overestimation of the prevalence of psychosomatic and psychological conditions or treatment effects). Finally, while this study corroborates findings about high rates of mental health problems in patients with post-COVID condition that partially improve during treatment, what this study cannot answer is the causal direction of effects. For example, it might be that mental health problems follow from the physical symptoms of post-COVID condition and resulting impairments in daily functioning [7]. However, it may also be that illness-related anxiety and dysfunctional symptom expectation contribute to persistence of physical post-COVID condition symptoms [29]. Relatedly, while preliminary findings suggest that rehabilitation interventions are superior to natural recovery [30], the current study did not include a control group of patients that were not treated or received an alternative treatment. Thus, changes from admission to discharge observed in current study cannot be causally attributed the pulmonary rehabilitation treatment.

Conclusion

The current study dovetails with findings about the high mental and physical burden of post-COVID condition. However, both mental and physical symptoms showed partial improvement during a specialized inpatient pulmonary rehabilitation treatment. While impaired mental health may follow from physical post-COVID condition symptoms, future studies need to address the role of pre-COVID–19 somatization tendencies in the development and maintenance of post-COVID condition.

Data Availability

The data and R code with which results can be reproduced are available at the Open Science Framework (https://doi.org/10.17605/OSF.IO/BYFZC).

Funding Statement

The author(s) received no specific funding for this work.

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PLoS One. 2025 Aug 26;20(8):e0330938. doi: 10.1371/journal.pone.0330938.r001

Author response to Decision Letter 0

Transfer Alert

This paper was transferred from another journal. As a result, its full editorial history (including decision letters, peer reviews and author responses) may not be present.

2 Sep 2024

Decision Letter 0

Kamal Sharma

31 Jan 2025

PONE-D-24-34925Mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID conditionPLOS ONE

Dear Dr. Meule,

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.

Hello,

It is an important paper looking at "Mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID condition". It is a well written paper however it needs to address important points for the scientific validation of the results as pointed out by the reviewer-

1. What Were there inclusion/exclusion criteria for the sample?

2. What was the  participants’ pre-COVID mental health conditions ?

3. What scoring systems have been  validated or are they widely used in COVID-related research?

4. What was the correlation between physical health with changes in mental health.

These and other comments need to be addressed for final review.

Thanks

Please submit your revised manuscript by Mar 17 2025 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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We look forward to receiving your revised manuscript.

Kind regards,

Kamal Sharma

Academic Editor

PLOS ONE

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Additional Editor Comments:

Hello,

It is an important paper looking at "Mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID condition". It is a well written paper however it needs to address important points for the scientific validation of the results as pointed out by the reviewer-

1. What Were there inclusion/exclusion criteria for the sample?

2. What was the participants’ pre-COVID mental health conditions ?

3. What scoring systems have been validated or are they widely used in COVID-related research?

4. What was the correlation between physical health with changes in mental health.

These and other comments need to be addressed for final review.

Thanks

[Note: HTML markup is below. Please do not edit.]

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

**********

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. 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

**********

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

**********

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:  Thank you for the opportunity to review the manuscript “Mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID condition.”

This study examined the mental and physical health characteristics of individuals undergoing inpatient pulmonary rehabilitation for post-COVID condition. Mental health conditions were prevalent in this sample, including somatoform syndrome, anxiety, depression, and PTSD. Pulmonary functioning was associated with better self-reported physical functioning at the beginning of the program, but not with mental health scores. Both mental and physical health indicators showed improvement from admission to discharge.

This study addresses a timely topic and provides valuable information about the mental and physical health burden of post-COVID condition, particularly in the context of rehabilitation. The study also evaluates a wide range of both mental and physical health outcomes and is strengthened by its pre and post-treatment assessments.

However, there are several areas where the manuscript could be strengthened, and I have a few questions regarding the methods. My comments are as follows:

Abstract:

- I would suggest including length of treatment in the abstract.

Introduction

- The introduction could be improved by more clearly articulating the study rationale and research gap addressed.

- It would also be strengthened by providing justification for focusing on pulmonary rehabilitation, specifically in relation to its potential impact on mental health.

- I would suggest discussing the bidirectional relationship between physical and mental health impairments to provide a stronger theoretical framework for the study.

Methods

- Were there inclusion/exclusion criteria for the sample?

- Are data on participants’ pre-COVID mental health conditions available?

- Are data on the time between COVID-19 infection and admission to rehabilitation available?

- Have these measures been validated or widely used in COVID-related research?

- Did changes in physical health during treatment corresponded with changes in mental health.

- Did duration of treatment predict any outcomes?

Discussion

- The introduction emphasizes the need to evaluate treatments for post-COVID condition, but the discussion does not fully tie findings back to treatment relevance.

- The discussion includes extensive comparisons to prevalence rates and scores shown in previous studies, which makes it challenging to discern the central takeaways from the current study. I would recommend streamlining comparisons to previous studies and focusing Focus on contextualizing the findings within the broader literature without overwhelming the reader with extensive numerical comparisons.

- The authors might say more about somatoform syndrome, as it may be less familiar to readers compared to anxiety and depression.

- I would suggest discussing the clinical and public health implications of the findings more thoroughly, especially in terms of rehabilitation and mental health care for post-COVID condition.

- The discussion could be strengthened by highlighting what is novel and unique about this study.

- While self-report bias is mentioned as a limitation, its potential impact on the study’s findings is not discussed.

**********

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.

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: No

**********

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PLoS One. 2025 Aug 26;20(8):e0330938. doi: 10.1371/journal.pone.0330938.r003

Author response to Decision Letter 1

31 Mar 2025

Editor’s comments:

1. What were the inclusion/exclusion criteria for the sample?

RESPONSE: There were no inclusion or exclusion criteria other than that patients were admitted for post-COVID condition, as outlined in the sample paragraph of the method section.

2. What were the participants’ pre-COVID mental health conditions?

RESPONSE: We have now added self-reported mental disorders before the first COVID infection to Table 1.

3. What scoring systems have been validated or are they widely used in COVID-related research?

RESPONSE: All of the used measures are widely used in COVID-related research (e.g., https://doi.org/10.1186/s12912-021-00800-2, https://doi.org/10.12688/f1000research.50781.1, https://doi.org/10.2147/PRBM.S329380, https://doi.org/10.1186/s12905-024-03102-2, https://doi.org/10.3389/fpsyt.2021.695678, https://doi.org/10.23937/2572-4037.1510049, https://doi.org/10.1080/21641846.2023.2295419, https://doi.org/10.1371/journal.pone.0293081, https://doi.org/10.1007/s12144-022-02833-5). However, we have restricted to citing only the most relevant studies in the discussion section.

4. What was the correlation between physical health with changes in mental health.

RESPONSE: We are not sure how to answer this question. Pulmonary functioning variables were only available at admission, as described in the method section. While there is one subscale of the SF-36 entitled “physical functioning”, the other subscales of the SF-36 as well as the PHQ-D also assess aspects of physical health or aspects for which physical and mental health cannot be clearly separated (e.g., somatoform syndrome/somatic symptoms severity, energy/fatigue, pain). Thus, we are not sure which correlations the editor is interested in but we would be happy to address this in another revision if the editor can clarify this.

Reviewer’s comments:

Abstract:

1. I would suggest including length of treatment in the abstract.

RESPONSE: We have now added mean length of treatment to the abstract.

Introduction:

2. The introduction could be improved by more clearly articulating the study rationale and research gap addressed.

RESPONSE: We have now expanded on this by explicitly describing three study aims and their rationale in the final paragraph of the introduction section.

3. It would also be strengthened by providing justification for focusing on pulmonary rehabilitation, specifically in relation to its potential impact on mental health.

RESPONSE: See response above.

4. I would suggest discussing the bidirectional relationship between physical and mental health impairments to provide a stronger theoretical framework for the study.

RESPONSE: See response above.

Methods:

5. Were there inclusion/exclusion criteria for the sample?

RESPONSE: There were no inclusion or exclusion criteria other than that patients were admitted for post-COVID condition, as outlined in the sample paragraph of the method section.

6. Are data on participants’ pre-COVID mental health conditions available?

RESPONSE: Yes, we have now added self-reported mental disorders before the first COVID infection to Table 1.

7. Are data on the time between COVID-19 infection and admission to rehabilitation available?

RESPONSE: We have now added to the sample description that “time between the first COVID infection and admission to the hospital approximately ranged between 1–3 years (as the exact date of the first COVID infection could not be exactly determined retrospectively, no precise numbers can be reported here).”

8. Have these measures been validated or widely used in COVID-related research?

RESPONSE: Yes, the PHQ-9/PHQ-15, PC-PTSD, and SF-36 are widely used in COVID-related research (e.g., https://doi.org/10.1186/s12912-021-00800-2, https://doi.org/10.12688/f1000research.50781.1, https://doi.org/10.2147/PRBM.S329380, https://doi.org/10.1186/s12905-024-03102-2, https://doi.org/10.3389/fpsyt.2021.695678, https://doi.org/10.23937/2572-4037.1510049, https://doi.org/10.1080/21641846.2023.2295419, https://doi.org/10.1371/journal.pone.0293081, https://doi.org/10.1007/s12144-022-02833-5). However, we have restricted to citing only the most relevant studies in the discussion section.

9. Did changes in physical health during treatment corresponded with changes in mental health?

RESPONSE: We are not sure how to answer this question. Pulmonary functioning variables were only available at admission, as described in the method section. While there is one subscale of the SF-36 entitled “physical functioning”, the other subscales of the SF-36 as well as the PHQ-D also assess aspects of physical health or aspects for which physical and mental health cannot be clearly separated (e.g., somatoform syndrome/somatic symptoms severity, energy/fatigue, pain). Thus, we are not sure which correlations the reviewer is interested in but we would be happy to address this in another revision if the reviewer can clarify this.

10. Did duration of treatment predict any outcomes?

RESPONSE: It did not, which we now report in Footnote 1.

Discussion:

11. The introduction emphasizes the need to evaluate treatments for post-COVID condition, but the discussion does not fully tie findings back to treatment relevance.

RESPONSE: We agree and have now restructured the discussion section (e.g., introduced subheadings) and have added more discussion about treatment effects.

12. The discussion includes extensive comparisons to prevalence rates and scores shown in previous studies, which makes it challenging to discern the central takeaways from the current study. I would recommend streamlining comparisons to previous studies and focusing Focus on contextualizing the findings within the broader literature without overwhelming the reader with extensive numerical comparisons.

RESPONSE: We agree and have now restructured and rewritten the first few paragraphs of the discussion section, for example, by removing the detailed numbers found in other studies and instead describe more broadly how the current findings compare to other studies.

13. The authors might say more about somatoform syndrome, as it may be less familiar to readers compared to anxiety and depression.

RESPONSE: We have now added to the description of the PHQ in the methods section that this refers to a pattern of multiple, recurrent, and frequently changing physical symptoms.

14. I would suggest discussing the clinical and public health implications of the findings more thoroughly, especially in terms of rehabilitation and mental health care for post-COVID condition.

RESPONSE: We have now expanded on this in the discussion section by discussing that, as inpatient treatment is more expensive than daypatient or outpatient treatment, future studies are needed that compare different treatment settings in terms of cost-benefit efficacy.

15. The discussion could be strengthened by highlighting what is novel and unique about this study.

RESPONSE: One new aspect is that we report on changes in self-reported mental and physical problems during a specialized inpatient pulmonary rehabilitation treatment. However, there are, of course, other similar studies und parts of the current manuscript report on findings that have been investigated in other studies as well. PLOS One’s policy is that novelty and uniqueness are no prerequisites for publication of scientific studies (https://everyone.plos.org/about-plos-one), similar to suggestions by others (https://doi.org/10.3389/fpsyg.2021.609802). Thus, we feel that highlighting novelty and uniqueness is not required or may even be inappropriate in light of the journal’s policy.

16. While self-report bias is mentioned as a limitation, its potential impact on the study’s findings is not discussed.

RESPONSE: We have now extended this sentence such that potential self-report biases may possibly lead to an overestimation of the prevalence of psychosomatic and psychological conditions or treatment effects.

Attachment

Submitted filename: comments.docx

pone.0330938.s002.docx (21KB, docx)

Decision Letter 1

Kamal Sharma

12 May 2025

PONE-D-24-34925R1Mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID conditionPLOS ONE

Dear Dr. Meule,

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.

Please submit your revised manuscript by Jun 26 2025 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.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Kamal Sharma

Academic Editor

PLOS ONE

Additional Editor Comments:

Hello,

As per the reviewers' comments please revise the manuscript and resubmit for consideration.

Thanks

[Note: HTML markup is below. Please do not edit.]

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

Reviewer #3: All comments have been addressed

**********

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

Reviewer #3: Partly

**********

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

Reviewer #2: Yes

Reviewer #3: No

**********

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: (No Response)

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

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: While the manuscript is much improved, I still have a few minor suggestions for the authors to consider in their final revision:

Clarify the clinical significance of symptom reduction, especially for PTSD and anxiety. A one-sentence addition noting whether changes meet known thresholds for clinical relevance would help contextualize the results for clinicians.

In Table 1, consider highlighting the mental health scales where improvement was statistically significant. Asterisking or bolding these values can guide readers better.

The addition of the correlation between pulmonary function and self-reported physical health is appreciated. Still, a short note in the Discussion section interpreting the lack of correlation between pulmonary function and mental health outcomes would add nuance to the findings.

Typographical Clean-Up: One or two sentences could benefit from slight tightening. Example: "Mental and physical problems partially remit..." could be refined to "Both mental and physical symptoms showed partial improvement

Reviewer #3: Previous Comment:

In extension to editor's comment 1. What were the inclusion/exclusion criteria for the sample? The answer could be all-comers, if there is no inclusion exclusion criteria.

New comments:

1. Please include severity of Covid infection, length of treatment, and ICU admission of patients at the time of COVID infection and in result section severity comparison on study results.

2. It is suggested to follow standard numerical presentation throughout the manuscript. e.g. in Measures section .81 should be replaced with 0.81.

3. Elaborate pulmonary rehabilitation treatment to patients in includes what type of treatment was given and length of treatment. 

4. Present manuscript is a small sample size but it mentioned Because of the numerous inferential tests and large sample size, we considered effects as significant at p < .005 (cf. Benjamin et al., 2018). Author needs to clarify how and why redefined p value 0.005 is applicable in the line of cited reference.

5. It has been 1.5 years since last follow-up and linger follow-up and comparison to baseline would be helpful.

6. Please provide the role of each author in present manuscript.

**********

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: Yes:  Elabbass Ali Abdelmahmuod

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. 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.

PLoS One. 2025 Aug 26;20(8):e0330938. doi: 10.1371/journal.pone.0330938.r005

Author response to Decision Letter 2

26 Jun 2025

Reviewer #2:

1. Clarify the clinical significance of symptom reduction, especially for PTSD and anxiety. A one-sentence addition noting whether changes meet known thresholds for clinical relevance would help contextualize the results for clinicians.

RESPONSE: We agree have reformulated and expanded on this in the “Changes from admission to discharge” section in the discussion section: “Somatic and depressive symptoms severity, generalized anxiety, and stress as assessed with the PHQ significantly decreased from admission to discharge with small-to-large effect sizes. In contrast, symptoms of panic disorder, eating disorders, and PTSD did not change from admission to discharge, suggesting that patients with post-COVID condition presenting with these symptoms require specialized psychotherapy in addition to pulmonary rehabilitation treatment.”

2. In Table 1, consider highlighting the mental health scales where improvement was statistically significant. Asterisking or bolding these values can guide readers better.

RESPONSE: Thank you for this suggestion. We believe the comment may refer to Table 2, as Table 1 presents only descriptive statistics. In Table 2, we have indeed included asterisks to indicate statistically significant correlation coefficients, and we fully agree that this enhances the table’s readability. Regarding the results on changes from admission to discharge, we reported the exact p-values in the table. For that reason, we decided not to use asterisks, as we felt they would be redundant in this context. For example, annotating a value with both “< 0.001” and a table note stating “p < .005” does not provide additional clarity, as the exact p-value already conveys that the result is statistically significant. We hope this explanation clarifies our approach, and we’re happy to adjust the presentation if further clarification is needed.

3. The addition of the correlation between pulmonary function and self-reported physical health is appreciated. Still, a short note in the Discussion section interpreting the lack of correlation between pulmonary function and mental health outcomes would add nuance to the findings.

RESPONSE: We agree and have added this sentence to the “Relationships between pulmonary functioning and self-report measures” section in the discussion section: “Thus, it appears that while persons with post-COVID condition report high rates of mental health issues, these do not seem to be directly attributable to impaired pulmonary functioning.”

4. Typographical Clean-Up: One or two sentences could benefit from slight tightening. Example: "Mental and physical problems partially remit..." could be refined to "Both mental and physical symptoms showed partial improvement

RESPONSE: We have now reformulated these sentences as suggested. 

Reviewer #3:

Previous Comment:

1. In extension to editor's comment 1. What were the inclusion/exclusion criteria for the sample? The answer could be all-comers, if there is no inclusion exclusion criteria.

RESPONSE: We have now reformulated this sentence as follows to be more precise: “Data of a consecutive sample of 141 persons who were infected with COVID–19 between 2020 and 2023 and who were admitted to inpatient pulmonary rehabilitation treatment for post-COVID condition at the Schön Klinik Berchtesgadener Land (Schönau am Königssee, Germany) between 16/01/2023 and 16/12/2023 were accessed on 19/06/2024 and analyzed. No additional inclusion or exclusion criteria were applied.”

New comments:

1. Please include severity of Covid infection, length of treatment, and ICU admission of patients at the time of COVID infection and in result section severity comparison on study results.

RESPONSE: Thank you for this comment. We would like to clarify that severity of COVID-19 infection—based on the WHO Ordinal Scale for Clinical Improvement—and whether patients were hospitalized is already presented in Table 1. The length of pulmonary rehabilitation treatment is also provided there. If the reviewer is referring instead to the duration of acute COVID-19 treatment at the time of initial infection, unfortunately, we do not have access to that information in our dataset. Regarding ICU admission, as shown in Table 1, the vast majority of patients (87%) received ambulatory care and were not hospitalized (data were missing for 4 individuals). Because of this strong imbalance—e.g., only 18 patients were hospitalized—it was not feasible to conduct meaningful comparisons in the inferential analyses. We hope this clarification is helpful and are happy to revise further if the reviewer had something different in mind.

2. It is suggested to follow standard numerical presentation throughout the manuscript. e.g. in Measures section .81 should be replaced with 0.81.

RESPONSE: We have now added the leading zeros to the decimal numbers for which we had previously omitted the leading zeros (i.e., decimal numbers that cannot exceed -1 or 1, cf. Publication Manual of the American Psychological Association 7th edition).

3. Elaborate pulmonary rehabilitation treatment to patients in includes what type of treatment was given and length of treatment.

RESPONSE: Thank you for this comment. We would like to point out that details on the pulmonary rehabilitation treatment are already included in the manuscript. Specifically, the “sample” section (first paragraph of the Methods) describes the key treatment components—namely diagnostic assessments, medical treatment, endurance and strength training, patient education, respiratory physiotherapy, relaxation techniques, occupational therapy, psychological support, and nutrition counseling (Gloeckl et al., 2021). Additionally, the length of treatment is reported in Table 1. We hope this addresses the reviewer’s suggestion, and we are happy to further clarify or elaborate if needed.

4. Present manuscript is a small sample size but it mentioned Because of the numerous inferential tests and large sample size, we considered effects as significant at p < .005 (cf. Benjamin et al., 2018). Author needs to clarify how and why redefined p value 0.005 is applicable in the line of cited reference.

RESPONSE: Thank you for raising this important point. We have reworded the sentence in the manuscript to read: “Because of the numerous inferential tests and large sample size, we considered effects as significant at p < 0.005, as has been recommended by Benjamin et al. (2018), who argue that this alpha level ‘represents “substantial” to “strong” evidence according to conventional Bayes factor classifications’ and ‘would reduce the false positive rate to levels we judge to be reasonable’ (p. 7).” We understand the reviewer’s concern regarding the characterization of the sample size. While it may be considered modest in absolute terms, we believe it is sufficiently large for the types of analyses conducted. Specifically, the sample provided ample statistical power to detect even small effect sizes in both between-person correlations and within-person pre-post comparisons. In these contexts, effects such as correlations below r = 0.3 and Cohen’s d below 0.5 reached significance at the adjusted alpha level of 0.005. We hope this clarification helps justify the chosen significance threshold, and we remain open to further adjustment or elaboration if needed.

5. It has been 1.5 years since last follow-up and linger follow-up and comparison to baseline would be helpful.

RESPONSE: Thank you for this valuable suggestion. We would be happy to clarify that although 1.5 years have passed since data collection was completed, collecting additional follow-up data is unfortunately not feasible. Specifically, our ethical approval did not include provisions for recontacting participants, and the data have been fully and irreversibly anonymized in accordance with those ethical standards. As such, while we agree that longer-term follow-up would indeed offer meaningful insights, this lies beyond the scope of the current study’s approved framework.

6. Please provide the role of each author in present manuscript.

RESPONSE: We had actually already indicated the author contributions in the submission system but have now additionally included these in the manuscript.

Attachment

Submitted filename: comments_auresp_2.docx

pone.0330938.s003.docx (18.7KB, docx)

Decision Letter 2

Kamal Sharma

8 Aug 2025

<p>Mental and physical health in persons receiving inpatient pulmonary rehabilitation treatment for post-COVID condition

PONE-D-24-34925R2

Dear Dr. Meule,

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Kamal Sharma

Academic Editor

PLOS ONE

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Hello,

After 2nd revision and acceptance by both the reviewers the new manuscript is good to proceed to editorial desk towards acceptance.

Thanks

Reviewers' comments:

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Reviewer #2: Minor Suggestions:

Abstract:

Consider including effect size or quantitative outcomes in the abstract to better reflect the strength of your findings.

Figures and Tables:

Ensure that all figures are of high resolution and labels are readable.

Add a brief legend to the primary outcome table to clarify group coding.

Discussion:

While your additions were valuable, consider briefly mentioning how your findings may inform national-level mental health policy in India or be adapted in similar LMIC settings.

Conclusion:

Slightly tighten the conclusion to emphasize policy implications and potential for scale-up.

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Acceptance letter

Kamal Sharma

PONE-D-24-34925R2

PLOS ONE

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    Attachment

    Submitted filename: comments.docx

    pone.0330938.s002.docx (21KB, docx)
    Attachment

    Submitted filename: comments_auresp_2.docx

    pone.0330938.s003.docx (18.7KB, docx)

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