This is a platform protocol designed to be flexible so that it is suitable for a range of interventions and settings within diverse health care systems and community settings with incorporation into clinical COVID-19 management programs and treatment plans if results achieve key study outcomes.

This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating interventions to address and improve exercise intolerance and post-exertional malaise (PEM) as manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC).

The focus of this protocol is to assess interventions that can improve exercise capacity, daily activities tolerance, and quality of life in patients with PASC.

Study interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix. Study intervention appendices may be added or removed according to adaptive design and/or emerging evidence.

The platform protocol enrolls participants who meet study eligibility criteria. After completing initial screening assessments, eligible participants are assigned to one of the study intervention appendices that are actively enrolling. Participants must meet certain criteria within a specific appendix in order to be included in that appendix. Once assigned to an appendix, eligible participants are randomized to either the study intervention group or a control group.

Inclusion Criteria:

• See NCT06404047 for RECOVER-ENERGIZE: Platform Protocol level inclusion and exclusion criteria which applies to this appendix

Additional Appendix A (Cardiopulmonary Rehabilitation (Exercise Intolerance)) Level Exclusion Criteria:

1. Known pre-existing postural orthostatic tachycardia syndrome, not related to SARS-CoV-2 infection
2. Known uncontrolled hypertension (blood pressure [BP] ≥ 160/100 mmHg at rest)
3. Any of the following within 4 weeks of enrollment - acute myocardial infarction, unstable angina, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema), acute pulmonary embolism, suspected dissecting aneurysm, severe hypoxemia at rest, thromboembolic event(s), any acute or chronic disorder that may affect exercise capacity or be aggravated by exercise (e.g., infection, exercise induced syncope, thyrotoxicosis, unable to cooperate)
4. Score of 2 or greater for both frequency and severity for any of the first 5 questions on the Screening mDSQ-PEM AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of > 14 hours in item 9 OR Score of 3 or greater on any severity question (regardless of frequency) AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of > 14 hours in item 9 OR Any score of 3 or greater on any of the severity questions on the mDSQ-PEM 48-72 hours following the Screening ISWT test
5. A selection of ≥ 8 on question 1 or ≥ 9 on question 3 of the OH Activity Scale from the mOHQ
6. Engaged in purposeful moderate or greater intensity exercise with the intent to improve one's health 2 or more times per week over the 30 days prior to informed consent
7. Inability to walk

The summary of the results will be shared on the study website: https://recovercovid.org/

The assessor of the primary outcome, Endurance Shuttle Walk Test (ESWT), is blinded.