The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome

Study Overview
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Brief Summary
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The SARS-CoV2 pandemic has kept the world in suspense for over a year now. Almost 100 million people around the world have contracted COVID-19 to date and over 2 million people have died of COVID-19 by the end of January 2021. Despite the tragedy of these deaths, it must be pointed out at this point that the number of COVID-19 survivors is significantly larger. These COVID-19 survivors are now the focus of interest in rehabilitation measures, as it has been shown that survival of the disease does not go hand in hand with a complete cure. Thirty-five percent of all COVID-19 survivors and 87% of the COVID-19 survivors who were hospitalized in the course of their illness suffer from after-effects that are currently summarized as post-COVID fatigue syndrome also known as Long-COVID. As health care workers are at higher risk of contracting SARS CoV2 and furthermore, considering their central role in the overcoming of this pandemic, a COVID-19 rehabilitation program for healthcare workers of the Medical University of Vienna, Austria as well as the General Hospital of Vienna, Austria - together the second-largest university-clinic in the world - was developed as part of workplace health promotion. Nowadays, the fatigue syndrome is primarily known as a side effect of cancer treatment and thus from the rehabilitation of cancer patients. Cancer-related fatigue is a massive limiting side effect for patients and the currently most effective treatment strategy against cancer-associated fatigue syndrome is physical training. The idea for this current project is, that physical exercise might have similar effects on post-SARS-CoV2 fatigue as it has on cancer-related fatigue. The current study evaluates the effects of this primarily exercise-based rehabilitation program on Long-COVID fatigue.

Detailed Description
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Employees of the Medical University of Vienna, Austria and the General Hospital of Vienna, Austria who survived a SARS-CoV2 infection will be invited to take part in an eight weeks post-COVID-19 rehabilitation program which is part of a workplace health promotion measure. This program consists of eight weeks of exercising (twice per week supervised resistance training + individual, heart-rate controlled endurance training recommendations) with a sports scientist and a sports medicine specialist, complemented by one session of nutrition consultation with a nutritionist and two sessions of psychological consultation with a clinical psychologist. Parallel to this workplace health promotion program, the scientific evaluation of this intevention will be undertaken via this study.

Official Title
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The Effects of a Multi-factorial Rehabilitation Program for Healthcare Workers Suffering From Post-COVID-19 Fatigue Syndrome

Conditions
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COVID-19

Intervention / Treatment
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* Other: Exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Employees of the Medical University of Vienna, Austria or the General Hospital of Vienna, Austria survived COVID-19 infection Exclusion Criteria: acute COVID-19 infection serious, uncontrolled diseases of the cardiovascular system insufficient language skills to complete the study requirements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Stratification regarding post-COVID-19 fatigue syndrome at baseline yes/no
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Post COVID-19 fatigue at baseline yes<br>SARS-CoV2 survivor who attends the exercise program and suffers from post-COVID-19 fatigue Syndrome according to the Post-Covid-19-Functional Scale (PCFS) | Other: Exercise<br>* 8 week exercise program, nutritional & psychological consultation<br>|
| Active Comparator: Post COVID-19 fatigue at baseline no<br>SARS-CoV2 survivor who attends the exercise program and doesn't suffer from post-COVID-19 fatigue Syndrome according to the Post-Covid-19-Functional Scale (PCFS) | Other: Exercise<br>* 8 week exercise program, nutritional & psychological consultation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of maximum oxygen uptake (VO2max) over time-points (baseline - 4 weeks - 8 weeks) assessed during cardio-pulmonary exercise testing (CPET) | Measurement of VO2max during an exhaustive CPET is the gold standard for objectifying cardiopulmonary performance and detecting any cardiovascular risks under stress. VO2max will be measured in ml/kg bodyweight.This examination is the gold standard for objectifying cardiopulmonary performance and detecting any cardiovascular risks under stress. | Baseline, 4 weeks, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of walking distance during a six minutes walk test (6MWT) over time-points (baseline - 4 weeks - 8 weeks) | The 6MWT is used, among other things, to assess and control cardiovascular and pulmonary performance below the anaerobic threshold. This test is used for the clinical evaluation of the basic motor property endurance and measures the distance a patient can walk as quickly as possible on a flat, hard surface in a period of 6 minutes. It will be measured in meters. | Baseline, 4 weeks, 8 weeks | 
| Change of numbers over time-points (baseline - 4 weeks - 8 weeks) how often someone can stand up and sit down on a chair within 30 seconds during a 30-seconds sit-to-stand test (30secSTS) | The 30seconds Sit-to-Stand test is a well-established functional test used to estimate the strength endurance of the lower extremities and describes how often the test person can get up from a chair and sit down again in a period of 30 seconds. In patients suffering from chronic obstructive pulmonary disease (COPD), the 30seconds sit-to-stand test has proven to be a valid and reliable parameter. | Baseline, 4 weeks, 8 weeks | 
| Change of absolute body fat over time-points (baseline - 4 weeks - 8 weeks) via Bioelectrical Impedance Analysis (BiA) | BiA is a non-invasive method for measuring body composition and serves as a basis for assessing metabolic disease risks among others by measuring body fat in absolute (kg) numbers. | Baseline, 4 weeks, 8 weeks | 
| Change of body fat percentage over time-points (baseline - 4 weeks - 8 weeks) via Bioelectrical Impedance Analysis (BiA) | BiA is a non-invasive method for measuring body composition and serves as a basis for assessing metabolic disease risks among others by measuring body fat in relative (%) numbers. | Baseline, 4 weeks, 8 weeks | 
| Change of absolute Lean Body Mass (LBM) over time-points (baseline - 4 weeks - 8 weeks) via Bioelectrical Impedance Analysis (BiA) | BiA is a non-invasive method for measuring body composition and serves as a basis for assessing metabolic disease risks among others by measuring lean body mass in absolute (kg) numbers. | Baseline, 4 weeks, 8 weeks | 
| Change of realtive Lean Body Mass (LBM) over time-points (baseline - 4 weeks - 8 weeks) via Bioelectrical Impedance Analysis (BiA) | BiA is a non-invasive method for measuring body composition and serves as a basis for assessing metabolic disease risks among others by measuring lean body mass in relative (%) numbers. | Baseline, 4 weeks, 8 weeks | 
| Change of generalized anxiety measured over time-points (baseline - 4 weeks - 8 weeks) via Generalized Anxiety Disorder Scale-7 (GAD-7) | The GAD-7 (Generalized Anxiety Disorder 7) is a module of the health questionnaire for patients (PHQ-D), which was designed to identify patients with generalized anxiety disorder and to record the severity of symptoms of generalized anxiety (7 items). Scores range from 0 to 21 points with low scores representing low general anxiety and high scores representing high general anxiety. | Baseline, 4 weeks, 8 weeks | 
| Change of depression measured over time-points (baseline - 4 weeks - 8 weeks) via the Patient Health Questionnaire-9 (PHQ-9) | The questionnaire PHQ-9 corresponds to the depression module of the health questionnaire for patients (PHQ-D). It was developed as a screening instrument for the diagnosis of depression for routine use in the somatic medical field (9 items). Scores range from 0 to 27 points with low scores representing low levels of depression and high scores representing high levels of depression. | Baseline, 4 weeks, 8 weeks | 
| Change of mental stress measured over time-points (baseline - 4 weeks - 8 weeks) via Perceived Stress Scale (PSS-10) | The PSS-10 measures the subjective experience of stress. It records the dimensions of self-efficacy and helplessness in two scales, as well as an overall stress score (10 items). Scores range from 0 to 50 points with low scores representing low stress levels and high scores representing high stress levels. | Baseline, 4 weeks, 8 weeks | 
| Change of fatigue measured over time-points (baseline - 4 weeks - 8 weeks) via Brief Fatigue Inventory (BFI) | The BFI measures the severity and extent of fatigue. The questionnaire covers six dimensions: activity, mood, ability to walk, work, relationship with other people and joie de vivre (10 items). Scores range from 0 to 10 points with low scores representing low fatigue and high scores representing high fatigue. | Baseline, 4 weeks, 8 weeks | 
| Change of resilience measured over time-points (baseline - 4 weeks - 8 weeks) via Brief Resilience Scale (BRS) | The Brief Resilience Scale measures resilience, the ability to successfully cope with difficult, stressful situations or to recover quickly from them (6 items). Scores range from 1 to 5 points with low scores representing low resilience and high scores representing high resilience. | Baseline, 4 weeks, 8 weeks | 
| Change and time kinetics of handgrip strength (HGS) over time-points (baseline and before each exercise session) measured via handgrip Dynamometer. | Data on the fist force in kg (measurement of the basic motor property force), which are collected using a JAMAR® dynamometer. | Baseline, and before every supervised resistance exercise session | 
| Change and time kinetics of physical and functional limitations of COVID-19 survivors over time-points (baseline and before each exercise session) via Post-Covid-19-Functional Scale (PCFS) | The Post-COVID-19 Functional Scale is a questionnaire for self-assessment of physical and functional limitations after a COVID-19 infection. It ranges from 0 (no functional impairment) to 4 (severe functional impairments). | Baseline, and before every supervised resistance exercise session | 
| Change of work ability over time-points (baseline, 4 weeks, 8 weeks) via Work Ability Index (WAI) questionnaire. | The Work Ability Index (WAI) is a measuring instrument for recording the work ability of employees. The WAI is a questionnaire that is filled out either by the respondents themselves or by third parties, e.g. company doctors during the company medical examination. The WAI is predictive of reintegration into working life after workplace-specific rehabilitation against back pain. WAI scores range from 7-27 (poor), over 28-36 (moderate), and 37 to 43 (good) to 44-49 (very good). | Baseline, 4 weeks, 8 weeks | 
| Change of troponin (TnT) over time-points (baseline - 4 weeks - 8 weeks) via blood sample. | TnT (0 - 14 ng/L) is a heart-specific and very sensitive marker for myocardial damage in case of elevated values | Baseline, 4 weeks, 8 weeks | 
| Change of BNP over time-points (baseline - 4 weeks - 8 weeks) via blood sample. | BNP (0 - 125 pg/ml) is increased in cardiac insufficiency and increased volume load on the heart | Baseline, 4 weeks, 8 weeks | 
| Change of CK-MB over time-points (baseline - 4 weeks - 8 weeks) via blood sample. | CK-MB (< 24 U/l) are elevated in cardiac muscle diseases e.g. myocardial infarction, myocarditis, ischemic conditions e.g. angina pectoris, or for the differential diagnosis of muscle diseases | Baseline, 4 weeks, 8 weeks | 
| Change of HS-CRP over time-points (baseline - 4 weeks - 8 weeks) via blood sample. | CRP (< 0,5 mg/dl) is an acute phase protein which increases in infections (bacterial, less viral and fungi), inflammation, post-OP, malignant processes; ultra-sensitive CRP is additionally a risk assessment marker of aterosclerosis | Baseline, 4 weeks, 8 weeks | 
| Change of IL-6 over time-points (baseline - 4 weeks - 8 weeks) via blood sample. | IL-6 (<= 7 pg/mL) is a mediator of the immune system and elevated in inflammatory processes | Baseline, 4 weeks, 8 weeks | 
| Change of cholesterol over time-points (baseline - 4 weeks - 8 weeks) via blood sample. | Cholesterol (< 200 mg/dL) is a risk factor for early atherosclerosis | Baseline, 4 weeks, 8 weeks | 
| Change of triglycerides over time-points (baseline - 4 weeks - 8 weeks) via blood sample. | Triglycerides (< 150 mg/dl) increased in primary hyperlipidemia as a risk faktor for cardiovascular diseases | Baseline, 4 weeks, 8 weeks | 
| Change of distance walked in meters per day over time | Spare time physical activity is a key indicator for physical function and will be measured via activity tracker | From the first exercise session over 8 weeks until the last exercise session (daily) | 
| Change of time of physical activity per day in minutes over time | Spare time physical activity is a key indicator for physical function and will be measured via activity tracker | From the first exercise session over 8 weeks until the last exercise session (daily) | 
| Change of step count per day over time | Spare time physical activity is a key indicator for physical function and will be measured via activity tracker | From the first exercise session over 8 weeks until the last exercise session (daily) | 
| Change of average heart rate per day over time | A low average heart rate during activities of daily living is an indicator for a relatively low cardiovascular load | From the first exercise session over 8 weeks until the last exercise session (daily) | 
| Change of maximum heart rate per day over time | A low maximum heart rate during activities of daily living is an indicator for a relatively lower level of cardiovascular load | From the first exercise session over 8 weeks until the last exercise session (daily) | 
| Change of average oxygen saturation (in %) per day over time | A high oxygen saturation is an indicator for a well functioning gas exchange in the lungs and distribution into the circulatory system | From the first exercise session over 8 weeks until the last exercise session (daily) | 
| Change of Mild Cognitive Impairment over time-points (baseline, 8 weeks) via Montreal Cognitive Assessment (MoCA) | The MoCA test is a screening instrument for Mild Cognitive Impairment. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. | Baseline, 8 weeks | 
| Change of sleep quality over time points (baseline, 4 weeks, 8 weeks) via Insomnia Severity Index (ISI) | The Insomnia Severity Index (ISI) is a brief self-report instrument measuring the patient's perception of both nocturnal and diurnal symptoms of insomnia. | Baseline, 4 weeks, 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Long-COVID, SARS-CoV fatigue syndrome, Exercise, Rehabilitation