Physiology of Long COVID-19 and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity

November 26, 2025 updated by: University of Colorado, Denver

Physiological Underpinnings of Post-Acute Sequelae of SARS CoV-2 ("Long COVID") and Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity

The primary objectives of this study are to determine whether exercise training is an effective strategy for treatment of Long COVID and characterize the cardiorespiratory and autonomic physiology in these patients to precisely characterize mechanisms contributing to this syndrome.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Abnormalities observed among Long COVID patients are consistent with cardiac deconditioning. The Long COVID syndrome has been attributed to dysautonomia and/or postural orthostatic tachycardia syndrome (POTS) based largely on anecdotal experience and observations of positional tachycardia among affected individuals. However, it has been emphasized that data are clearly lacking to implicate dysautonomia alone as the cause of Long COVID. Alternatively, cardiac deconditioning leads to a constellation of symptoms, including exercise intolerance, brain fog/cognitive impairments, tachycardia and orthostatic intolerance, all of which are reported among reported among patients with Long COVID. Multiple studies have demonstrated that cardiac deconditioning may occur with as little as 20 hours of bedrest. Exercise training improves cardiorespiratory performance among patients suffering from cardiac deconditioning. Exercise training improves HR regulation and cardiovascular function during submaximal and peak exercise, and improves overall exercise capacity particularly among individuals with cardiac deconditioning following bedrest (e.g. Dallas bedrest studies) and among individuals with postural orthostatic tachycardia syndrome. Our preliminary data demonstrate a significant improvement/resolution in Long-COVID symptoms following a twelve-week exercise training program in a community setting. During the height of the COVID pandemic, the investigators developed an exercise protocol that has been used in the clinical setting to assist with management of patients suffering from Long COVID. This protocol involves recumbent/semi-recumbent exercise - specifically, rowing or cycling on a recumbent ergometer.

This proposal involves a clinical trial involving a two-aim initiative whereby participants with Long COVID will be randomized to a 12-week period of exercise training v. usual care ("controls") with baseline and follow-up assessments in order to: 1) Determine whether exercise training is an effective treatment strategy for management of Long COVID (Aim 1); and 2) Characterize cardiovascular/autonomic physiology among patients with Long COVID (Aim 2). In a third aim, healthy individuals will undergo a hemodynamic assessment afterbefore and after 24 hours of bedrest. The hemodynamic assessment will be identical to participants with Long COVID.

There will be a baseline assessment (Visit1) for all participants. After the baseline assessment, participants will be randomized in a 1:1 fashion to either undergo an exercise training program (exercise group) or usual care (control group) with no intervention. After completion of the exercise training program, the exercise group will return for a follow-up assessment (Visit2) that will be identical to the baseline (Visit 1) assessment. Participants in the control group will return for a follow-up (Visit 2) assessment, after which time they will crossover to complete the exercise training program. After completion of the exercise training program, these participants will return for a follow-up assessment (Visit 3). So, participants in the exercise group will complete two visits; participants in the control group will complete three visits.

Each assessment (Visits 1,2 and 3) is identical and includes a baseline resting assessment, watching heart rate and blood pressure while laying flat, as well as a tilt table test, a 10-minute stand, and an exercise test. Participants also complete a questionnaire asking about quality-of-life. The visit lasts about 2-2.5 hours.

The exercise training program is about twelve weeks long. Participants are provided exercise equipment at home, to complete the program. The program involves recumbent exercise (e.g. rowing machine, or recumbent cycling) and starts off with low duration, low intensity exercise, and gradually increases in duration and intensity over time.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University of Colorado Hospital
        • Contact:
          • William K Cornwell, III, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Adults ≥18 years with documented history of COVID-19 infection and symptoms consistent with Long COVID lasting >12 weeks after diagnosis.

Exclusion Criteria:

  • History of cardiovascular/pulmonary disease prior to infection
  • COVID-related myocardial injury such as evidence of myocarditis
  • Deep vein thrombosis/pulmonary embolism following COVID-19 infection
  • Exercise intolerance resulting from conditions that are not related to cardiorespiratory or autonomic factors (e.g. osteoarthritis or other musculoskeletal diseases);
  • Dependency of supplemental oxygen following COVID infection due to cardiovascular and/or pulmonary complications following acute COVID infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Control
Experimental: Exercise
Behavioral: Exercise
exercise protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Characterizing the impact of exercise training (cardiac rehabilitation) on functional capacity among patients with Long COVID
Time Frame: 12 weeks
functional capacity as determined by VO2max
12 weeks
Characterizing the impact of exercise training (cardiac rehabilitation) on HRqOL among patients with Long COVID
Time Frame: 12 weeks
Health-related quality of life (HRqOL) from SF-36 form; all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
orthostatic challenge
Time Frame: 12 weeks
Heart rate during orthostatic challenge
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Colorado, Denver

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2023

Primary Completion (Estimated)

October 31, 2027

Study Completion (Estimated)

October 31, 2027

Study Registration Dates

First Submitted

September 30, 2022

First Submitted That Met QC Criteria

September 30, 2022

First Posted (Actual)

October 4, 2022

Study Record Updates

Last Update Posted (Estimated)

December 4, 2025

Last Update Submitted That Met QC Criteria

November 26, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 22-1093

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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