Symptom-based Rehabilitation Compared to Usual Care in Post-COVID - a Randomized Controlled Trial

Study Overview
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Brief Summary
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Inpatient, multimodal rehabilitation represents one of the most important interventions in the disease management of post/long COVID. Different professional societies, including the German Society of Pneumology and the European Respiratory Society, recommend rehabilitation intervention to reduce the sequelae of COVID-19. However, from the perspective of science and practice, there are relevant areas that have been insufficiently investigated and are essential for the treatment success of post/long COVID patients: Differentiation of rehabilitation effects from natural recovery after COVID-19. Lack of personalized and symptom-based treatment approaches that can address the heterogeneity of symptoms in post/long COVID Lack of uniform, high-quality rehabilitation standards in post-/long-COVID. Therefore, post-COVID patients will be recruited at several post-COVID practices around Germany and randomized to receive (A) a rehabilitation program or (B) usual care. The primary objective of this randomized controlled trial (RCT) is to investigate whether a 3-week symptom-oriented, inpatient, multidisciplinary rehabilitation intervention, whose content focus is standardized according to cluster assignment (fatigue, cognition, soma), has a positive effect on the quality of life (primary outcome) in post-COVID syndrome patients compared to a usual care group (standard outpatient care). All study participants will be provided with a continuous telemonitoring system (SaniQ app) throughout the study period. After the interventional phase, there will be a 3 months follow-up assessment to evaluate the maintenance effects of COVID rehabilitation.

Official Title
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Symptom-based Rehabilitation Compared to Usual Care in Post-COVID - a Randomized Controlled Trial

Conditions
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COVID-19, Long-COVID

Intervention / Treatment
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* Other: symptom-focused rehabilitation
* Other: usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-COVID Syndrome according to World Health Organisation definition (persistent symptoms for at least 3 months after PCR-test confirmed SARS-CoV 2 infection) Exclusion Criteria: no walking ability not able to operate smartphone apps rehabilitation program within the previous 6 months

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: Symptom-focused Rehabilitation<br>Patients in this arm will be referred to a 3-week inpatient comprehensive rehabilitation program. Initially, patients will be classified into one out of three clusters namely: Cluster A (Fatigue), Cluster B (cognition), or Cluster C (physical). The content of the rehabilitation program will be individually adapted according to the patient's most relevant symptom cluster. | Other: symptom-focused rehabilitation<br>* Patients in this arm will be referred to a 3-week inpatient comprehensive rehabilitation program. Initially, patients will be classified into one out of three clusters namely: Cluster A (Fatigue), Cluster B (cognition), or Cluster C (physical). The content of the rehabilitation program will be individually adapted according to the patient's most relevant symptom cluster.<br>|
| Other: Usual Care<br>Patients in this arm do not receive any intervention beyond usual care during the study phase. However, all patients in this group will get the opportunity to also receive a rehabilitation program after the study phase. | Other: usual care<br>* Patients in this arm do not receive any intervention beyond usual care during the study phase. However, all patients in this group will get the opportunity to also receive a rehabilitation program after the study phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Quality of life assessed by Short Form - 12 Questionnaire at week 4 and week 12 | the scale of the physical and mental Health component summary score ranges from minimum 0 to maximum 100 points with higher scores indicating better quality of life | baseline, week 4, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline COVID-related symptoms at week 4 and week 12 | the number of COVID-symptoms will recorded as well as their intensity will be rated on a scale from 0 [not relevant] until 10 [very severe symptom]. | baseline, week 4, week 12 | 
| Change from baseline lung function at week 4 and week 12 | following Parameters will be collected: forced expiratory volume in 1 sec, peak flow, forced vital capacity, total lung capacity, diffusion lung capacity for carbonmonoxide | baseline, week 4, week 12 | 
| Change from baseline blood gas analysis at week 4 and week 12 | following parameters will be collected at rest and at the end of an incremental cycle test: partial pressure for oxygen and carbon dioxide | baseline, week 4, week 12 | 
| Change from baseline Cardiac Doppler echocardiography at week 4 and week 12 | Left and right heart echocardiography will be performed | baseline, week 4, week 12 | 
| Change from baseline laboratory parameters at week 4 and week 12 | blood samples will be taken from venous blood | baseline, week 4, week 12 | 
| Change from baseline exercise performance at week 4 and week 12 | incremental cardiopulmonary exercise testing will be performed with spirometry | baseline, week 4, week 12 | 
| Change from baseline health care service needs at week 4 and week 12 | Number of visits at the general practitioner, pulmonologist, psychologist, physiotherapist, COVID-ambulance, hospital admission until the last visit will be recorded | baseline, week 4, week 12 | 
| Change from baseline working capability at week 4 and week 12 | number of days of incapacity to work until the last visit will be recorded | baseline, week 4, week 12 | 
| Change from baseline sleep quality at week 4 and week 12 | Sleep quality will be assessed by using the Pittsburgh Sleep Quality Index (total score ranges from 0 to 21 with higher scores indicating higher impairment) | baseline, week 4, week 12 | 
| Change from baseline sleep quality at week 4 and week 12 | daytime sleepiness will be assessed by using the Epworth Sleepiness Scale (total score ranges from 0 to 24 with higher scores indicating higher impairment) | baseline, week 4, week 12 | 
| Change from baseline Depression status assessed by Patient Health Questionnaire 9 | the total score ranges from 0 to 27 points with higher scores indicating worse Depression symptoms | baseline, week 4, week 12 | 
| Change from baseline Depression status assessed by Generalized Anxiety Disorder Scale 7 | the total score ranges from 0 to 21 points with higher scores indicating more anxiety symptoms | baseline, week 4, week 12 | 
| Change from baseline resilience assessed by resilience scale 13 | the total score ranges from 13 to 91 points with higher scores indicating higher resilience | baseline, week 4, week 12 | 
| Change from baseline cognitive status assessed by Montreal Cognitive Assessment Test | the total score ranges from 0 to 30 points with higher scores indicating a better cognitive status | baseline, week 4, week 12 | 
| Change from baseline dyspnea assessed by Modified Medical Research Counsil score at week 4 and week 12 | the total score ranges from 0 to 4 points with higher scores indicating more dyspnea | baseline, week 4, week 12 | 
| Change from baseline dysfunctional breathing assessed by Nijmegen breathing questionnaire at week 4 and week 12 | the total score ranges from 0 to 64 points with higher scores indicating hyperventilation | baseline, week 4, week 12 | 
| Change from baseline chronic fatigue syndrome assessed by fatigue assessment scale at week 4 and week 12 | the total score ranges from 10 to 50 points with higher scores indicating more fatigue | baseline, week 4, week 12 | 
| Change from baseline chronic fatigue syndrome assessed by canadian consensus criteria at week 12 | the canadian consensus criteria indicate if patients developed a chronic fatigue syndrome/myalgic encephalomyelitis | baseline, week 12 | 
| Change from baseline functional status assessed by post-COVID functional status scale at week 4 and week 12 | the total score ranges from 0 to 4 points with higher scores indicating more impairment | baseline, week 4, week 12 | 
| Change from baseline physical activity assessed by Garmin watch at week 4 and week 12 | daily total steps per day will be recorded by a Garmin watch linked to the SaniQ App | baseline, week 4, week 12 | 
| Change from baseline blood pressure assessed at week 4 and week 12 | blood pressure will be measured at the upper arm using the Aponorm device | baseline, week 4, week 12 | 
| Change from baseline oxygen saturation assessed by pulse oximeter at week 4 and week 12 | Beurer pulse oximeter | baseline, week 4, week 12 | 
| Change from baseline peak flow assessed by peak flow meter at week 4 and week 12 | peak flow will be assessed by smart one spirometer | baseline, week 4, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rehabilitation, intervention, quality of life, long-COVID, post-COVID syndrome, sequelae, recovery