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

The primary objectives of this study are to establish exercise training as a novel intervention to treat Long COVID and characterize the cardiorespiratory and autonomic physiology in these patients to precisely characterize mechanisms contributing to this syndrome.

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) Establish exercise training as a novel treatment strategy for management of Long COVID (Aim 1); and 2) Characterize cardiovascular/autonomic physiology among patients with Long COVID (Aim 2).

There will be a total of 4 visits for testing.

* Baseline Evaluation

  * Visit 1: non-invasive baseline assessment. Visit length \~2 hours.
  * Visit 2: invasive baseline assessment. Visit length \~3 hours.
  * Visit 3: non-invasive, post-exercise assessment. Protocol identical to Visit 1
  * Visit 4: invasive, follow-up assessment. Protocol identical to Visit 2.
* Following completion of Visits 1 and 2, participants will be randomized in a 1:1 ratio to either: 1) Twelve weeks of exercise training (N=15); or 2) Twelve weeks of conservative management (N=15). Thereafter, all participants will complete follow-up evaluation with noninvasive assessment (Visit 3) and invasive assessment (Visit 4), identical to the protocol for Visits 1-2.

Eligibility Criteria:
Inclusion Criteria:

* Adults ≥18 years with documented history of COVID-19 infection and symptoms consistent with Long COVID lasting \>4 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
* body mass index \> 35kg/m2
* age of greater than 65 years.