Sequelae of COVID-19 With Focus on Exercise Capacity and Underlying Mechanisms (COR-PHYS)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Controls; Patients Post-COVID-19
• 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

• Study Type: Observational
• Enrollment (Anticipated): 128

Contacts and Locations

Study Locations

• Switzerland
  • BS
    • Basel, BS, Switzerland, 4052
      • Recruiting
      • Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, University of Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Previously hospitalised patients recovering from COVID-19 and fully vaccinated controls with no history of symptomatic COVID-19.

Recruitment of patients will be done via the University Hospital of Basel, Switzerland, the Clinic Barmelweid, Barmelweid, Switzerland, and Cantonal Hospital Olten, Olten, Switzerland. Participants for the control group will be recruited prospectively through unaddressed letters distributed in the Basel-Stadt area, newspaper, internet-based media, and word-of-mouth. Recruitment will continue until the number of valid datasets corresponds to the calculated sample size.

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
COVID-19 (18 months post-infection); 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; Cardiopulmonary exercise testing; Diagnostic test: Lung function; Body plethysmography; Diagnostic test: Muscular strength and balance tests; Handgrip strength test, mid-thigh pull test and standing balance test in static tandem stance; Diagnostic test: Micro- and macrovascular endothelial function and cardiac function; Measurement of flow-mediated dilation, static and dynamic retinal vessel analysis, echocardiography; Diagnostic test: Blood sampling and analysis; Blood sampling by venepuncture; Diagnostic test: Physical activity; Physical activity surveillance using accelerometers; Diagnostic test: Questionnaires; 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; Diagnostic test: Body composition; Dual-energy x-ray absorptiometry (DXA)
Control group; Age-, sex-, and comorbidity-matched (frequency matching), fully vaccinated individuals with no history of symptomatic SARS-CoV-2 infection.	Diagnostic test: Cardiorespiratory fitness; Cardiopulmonary exercise testing; Diagnostic test: Lung function; Body plethysmography; Diagnostic test: Muscular strength and balance tests; Handgrip strength test, mid-thigh pull test and standing balance test in static tandem stance; Diagnostic test: Micro- and macrovascular endothelial function and cardiac function; Measurement of flow-mediated dilation, static and dynamic retinal vessel analysis, echocardiography; Diagnostic test: Blood sampling and analysis; Blood sampling by venepuncture; Diagnostic test: Physical activity; Physical activity surveillance using accelerometers; Diagnostic test: Questionnaires; 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; Diagnostic test: Body composition; Dual-energy x-ray absorptiometry (DXA)

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

Collaborators and Investigators

• Sponsor: Arno Schmidt-Trucksäss

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 3, 2023
• Primary Completion (ANTICIPATED): March 1, 2024
• Study Completion (ANTICIPATED): March 1, 2024

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (ACTUAL): November 12, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 8, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Coronavirus; Cardiopulmonary exercise testing; Sequelae; Exercise intolerance
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: EKNZ 2021-01039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No