Sequelae of COVID-19 With Focus on Exercise Capacity and Underlying Mechanisms

Study Overview
=================
Brief Summary
-----------------
The project is designed as a cross-sectional study and aims to examine long-term consequences of coronavirus disease 2019 (COVID-19) for selected bio-behavioural parameters while taking the disease course severity into account.

Official Title
-----------------
COVID-19 Severity, Long-term Consequences for Exercise Capacity and Link to Associated Mechanisms

Conditions
-----------------
Patients Post-COVID-19, Controls

Intervention / Treatment
-----------------
* Diagnostic Test: Cardiorespiratory fitness
* Diagnostic Test: Lung function
* Diagnostic Test: Muscular strength and balance tests
* Diagnostic Test: Micro- and macrovascular endothelial function and cardiac function
* Diagnostic Test: Blood sampling and analysis
* Diagnostic Test: Physical activity
* Diagnostic Test: Questionnaires
* Diagnostic Test: Body composition


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: tested positive for SARS-CoV-2 using antigen- or PCR tests within the last 18 months previous hospitalisation due to COVID-19 fully vaccinated (only for controls) Exclusion Criteria: inability to follow the study procedures (e.g. due to language barriers, psychological disorders, dementia, etc.), known pregnancy or lactating women, presence of any contraindications for exercising until maximum exhaustion, including insufficient blood pressure control (systolic >170 mmHg, diastolic >100 mmHg), ongoing cancer treatment, unstable angina pectoris, uncontrolled bradyarrhythmia or tachyarrhythmia, severe uncorrected valvular heart disease, clinically relevant acute infection, any form of musculoskeletal injury, participating in any interventional clinical trial within the last four weeks, previous participation in the current study history of symptomatic COVID-19 (only for controls)

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| COVID-19 (18 months post-infection)<br>Individuals with a positive Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) antigen-/polymerase chain reaction (PCR) test within the last 18 months that required hospitalisation. Symptoms typically worsened within a period of 5 to 10 days leading to e.g., prolonged fever, feeling of sickness and/or shortness of breath. This also includes individuals hospitalised in an intensive care ward. Individuals need to be hospitalised due to COVID-19 and not only with COVID-19. | Diagnostic Test: Cardiorespiratory fitness<br>* Cardiopulmonary exercise testing<br>Diagnostic Test: Lung function<br>* Body plethysmography<br>Diagnostic Test: Muscular strength and balance tests<br>* Handgrip strength test, mid-thigh pull test and standing balance test in static tandem stance<br>Diagnostic Test: Micro- and macrovascular endothelial function and cardiac function<br>* Measurement of flow-mediated dilation, static and dynamic retinal vessel analysis, echocardiography<br>Diagnostic Test: Blood sampling and analysis<br>* Blood sampling by venepuncture<br>Diagnostic Test: Physical activity<br>* Physical activity surveillance using accelerometers<br>Diagnostic Test: Questionnaires<br>* Global physical activity questionnaire (GPAQ), short-form 8 health survey (SF-8), barriers to physical activity, fatigue assessment scale (FAS), modified medical research council dyspnea scale (mMRC), depression, anxiety, and stress scale (DASS21), post-COVID-19 syndrome symptoms<br>Diagnostic Test: Body composition<br>* Dual-energy x-ray absorptiometry (DXA)<br>|
| Control group<br>Age-, sex-, and comorbidity-matched (frequency matching), fully vaccinated individuals with no history of symptomatic SARS-CoV-2 infection. | Diagnostic Test: Cardiorespiratory fitness<br>* Cardiopulmonary exercise testing<br>Diagnostic Test: Lung function<br>* Body plethysmography<br>Diagnostic Test: Muscular strength and balance tests<br>* Handgrip strength test, mid-thigh pull test and standing balance test in static tandem stance<br>Diagnostic Test: Micro- and macrovascular endothelial function and cardiac function<br>* Measurement of flow-mediated dilation, static and dynamic retinal vessel analysis, echocardiography<br>Diagnostic Test: Blood sampling and analysis<br>* Blood sampling by venepuncture<br>Diagnostic Test: Physical activity<br>* Physical activity surveillance using accelerometers<br>Diagnostic Test: Questionnaires<br>* Global physical activity questionnaire (GPAQ), short-form 8 health survey (SF-8), barriers to physical activity, fatigue assessment scale (FAS), modified medical research council dyspnea scale (mMRC), depression, anxiety, and stress scale (DASS21), post-COVID-19 syndrome symptoms<br>Diagnostic Test: Body composition<br>* Dual-energy x-ray absorptiometry (DXA)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiorespiratory fitness (as % of predicted V̇O2max) | Measured during cardiopulmonary exercise testing on a cycle ergometer. | 1.5 hours after inclusion in study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume in 1 s (as % of predicted) | Measured during bodyplethysmography. | 1.5 hours after inclusion in study | 
| Forced vital capacity (as % of predicted) | Measured during bodyplethysmography. | 1.5 hours after inclusion in study | 
| Total lung capacity (as % of predicted) | Measured during bodyplethysmography. | 1.5 hours after inclusion in study | 
| Diffusion capacity of the lungs (as % of predicted) | Measured during bodyplethysmography. | 1.5 hours after inclusion in study | 
| Muscle oxygenation at peak exercise (in %) | Measured using near-infrared spectroscopy during cardiopulmonary exercise testing on a cycle ergometer. | 1.5 hours after inclusion in study | 
| Cardiac output at peak exercise (in mL) | Measured non-invasive using the PhysioFlow device during cardiopulmonary exercise testing on a cycle ergometer. | 1.5 hours after inclusion in study | 
| Handgrip strength (in N) | Measured by a handheld dynamometer. | 1 hour after inclusion in study | 
| Handgrip rate of force development (in N/s) | Measured by a handheld dynamometer. | 1 hour after inclusion in study | 
| Macrovascular flow-mediated dilation at rest (in %) | Measured by ultrasound. | 0.5 hours after inclusion in study | 
| Microvascular flow-mediated dilation at rest (in %) | Measured by retinal vessel analysis. | 2 to 14 days after inclusion in study | 
| Fatigue Assessment Scale (FAS) score | Scores range from 5 to 50 with higher scores indicating more severe fatigue. | 2 to 14 days after inclusion in study | 
| Score of depression, anxiety, and stress questionnaire (DASS21) | Scores range from 0 to 63 with higher scores indicating worse mental health. | 2 to 14 days after inclusion in study | 
| Health distance | The statistical (Mahalanobis) distance (health distance) is a composite measure of various health biomarkers | Calculated during statistical analysis | 
| Cerebral oxygenation at peak exercise (in %) | Measured using functional near-infrared spectroscopy during cardiopulmonary exercise testing on a cycle ergometer. | 1.5 hours after inclusion in study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SARS-CoV-2, Coronavirus, Sequelae, Exercise intolerance, Cardiopulmonary exercise testing