Pulmonary Rehabilitation for Long COVID (Post COVID-19 Condition)

Study Overview
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Brief Summary
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In the PuRe COVID study (a randomized, controlled, multicenter, pragmatic trial) the investigators aim to assess the effect of a pulmonary rehabilitation program in primary care on exercise capacity (6MWT) and daily life physical activity in patients with long COVID. 134 patients with long COVID, defined by self-reported persistent COVID related symptoms ≥6 weeks after COVID-19 infection and a positive symptom score (CAT score ≥10 or mMRC score ≥2 or CIS-fatigue ≥36 or PCFS score of ≥2), will be recruited and divided into an intervention group or a control group. The intervention group will get twelve weeks of primary care pulmonary rehabilitation (PR) including coaching by primary care physiotherapists. The control group consists of usual care, which does not include a pulmonary rehabilitation program. This study will help determine whether the type of symptoms or affected body system can impact recovery form long covid during rehabilitation and after follow-up. The investigators will analyze determinants and risk factors that characterize non-responders and non-adherers to better understand which patients with long COVID benefit from rehabilitation.

Official Title
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Changes in Functional Exercise Capacity After PUlmonary REhabilitation in Primary Care: a Randomized, Controlled, Multicenter, Pragmatic Trial in 134 Patients With Long COVID (PuRe-COVID)

Conditions
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COVID-19, Long COVID, Post COVID-19 Condition

Intervention / Treatment
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* Other: Pulmonary rehabilitation in primary care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with status post COVID-19 (positive COVID-19 PCR or an official pharmacy performed antigen test or a self-performed test confirmed by a physician during the acute COVID-19 ≥ 6 weeks ago or positive antibodies before vaccination or positive antibodies before vaccination). Persistent COVID related symptoms that were not present pre-COVID-19 or were less severe pre-COVID. Symptomatic: quantified by dyspnea on exertion, loss of energy, fatigue or sleep impairment based upon the score of four questionnaires: COPD Assessment Test (CAT) ≥10, and/or modified Medical Research Council dyspnea scale (mMRC) ≥2, and/or CIS-fatigue ≥36, and/or post-COVID-19 Functional Status (PCFS) ≥2. Exclusion Criteria: Patients with known or self-reported cognitive, hearing, visual, neurological or musculoskeletal conditions that make it impossible to participate in pulmonary rehabilitation. Prior physiotherapy for long COVID if: patients who have completed ≥9 sessions of physiotherapy in total for long COVID. patients who completed any physiotherapy session in the previous 12 weeks for long COVID (primary care or hospital based; pulmonary or non-pulmonary). Patients with predominantly neurological disorders impacting respiratory function will not be eligible for the study. Patients that are not able to give informed consent or not able to complete questionnaires. Patients who have had any organ transplatation in the past, have to undergo any transplantation or are on an active transplantation list. Patients with active malignancy and/or (maintenance) treatment for active malignancy or curatively treated carcinoma within the past year.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pulmonary rehabilitation group<br>The intervention group receives a 12 weeks pulmonary rehabilitation program supervised by a primary care physiotherapist consisting of maximum 36 sessions (3 sessions per week). | Other: Pulmonary rehabilitation in primary care<br>* Pulmonary rehabilitation consists breathing exercises, exercise capacity, muscle strength and change towards an active lifestyle.<br>|
| No Intervention: Control group without rehabilitation<br>The control group will receive usual care that doesn't include pulmonary rehabilitation or a supervised physical activity program. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise capacity | Change in functional exercise capacity measured by 6-minute walk test (6MWT). | Baseline - 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in physical activity | Change in physical activity as objectively measured by an activity tracker (number of steps). | Baseline - 12 weeks | 
| Change in COVID-19 related symptoms | The COVID-19 related symptoms will be measured with the COPD assessment test (CAT). The total CAT score ranges from 0 to 40 where 0 represents no symptoms and 40 very bad symptoms. | Baseline - 12 weeks - 24 weeks - 36 weeks | 
| Change in quality of life | The quality of life will be measured with the EQ-5D-5L. | Baseline - 12 weeks - 24 weeks - 36 weeks | 
| Change in fatigue | The changes of the level of fatigue will be measured with the Checklist Individual Strength -fatigue (CIS-fatigue) score. The total CIS-fatigue score ranges from 20 to 140 where 20 represents no symptoms and 140 very bad symptoms. | Baseline - 12 weeks - 24 weeks - 36 weeks | 
| Change in dyspnoea | Changes in dyspnoea, measured with the modified medical research council (mMRC). The total mMRC scale ranges from 0 to 4 score where 0 represents no dyspnoea and 4 a lot of dyspnoea. | Baseline - 24 weeks - 36 weeks | 
| Change in functional status | The functional status will be measured by the post COVID-19 functional status scale (PCFS). It is an ordinal score ranging from 0 to 4 where 4 means the patient has a lot of limitations in daily life. | Baseline - 12 weeks - 24 weeks - 36 weeks | 
| Change in work productivity and activity impairment. | This will be measured with the work productivity and activity impairment questionnaire (WPAI), consisting of 6 questions. | Baseline - 24 weeks - 36 weeks | 
| Change in anxiety and depression symptoms. | This will be measured by the Hospital Anxiety and depression scale (HADS). The HADS is a fourteen item scale. Seven of the items relate to anxiety and seven relate to depression. The anxiety and depression subscales each range from 0 to 21, with higher scores indicating higher anxiety/depression complains. Patients were defined as having anxiety or depression or both if the score was 8 or more in the corresponding subscale. | Baseline - 24 weeks - 36 weeks | 
| Change in dysfunctional breathing | This will be measured with the Nijmegen questionnaire. 16 questions will be asked, ranging from 0 to 4. The higher the score, the more likely it is that they have dysfunctional breathing. | Baseline - 24 weeks - 36 weeks | 
| Change in exercise capacity | The functional exercise capacity will be measured by 6-minute walk test (6MWT). | Baseline - 24 weeks | 
| Predictors of response in 6- minute walk distance (6MWD) | The predictors will be based on baseline symptom scores (CAT, mMRC, CIS), baseline 6MWD and hospitalisation status. | Post pulmonary rehabilitation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary rehabilitation, Physiotherapy, Respiratory physiotherapy