RECOVER-ENERGIZE is studying possible treatments, also called study interventions, for exercise intolerance and post-exertional malaise (PEM) related to Long COVID. These studies will include adults who had COVID and who still have exercise intolerance or PEM symptoms.


Exercise Intolerance:
shortness of breath, muscle weakness, or extreme tiredness that causes the person to stop physical activity.

Post-Exertional Malaise (PEM):
exercise intolerance, difficulty thinking, trouble sleeping, sore throat, headaches, muscle aches, dizziness, or severe tiredness after minimal physical, mental, social, or emotional activity. These symptoms may get worse 12 to 48 hours after an activity and may last for days or even weeks.

After answering questions about PEM symptoms, participants will be enrolled in 1 of 2 clinical trials to learn if the study program improves their Long COVID symptoms. Within these studies, participants will have an equal chance of being assigned to an active study program group or to a control group.

RECOVER-ENERGIZE Exercise Intolerance (Personalized Cardiopulmonary Rehabilitation): a program for participants without PEM that combines exercises to help the heart and lungs work better with education to help participants improve their quality of life and ability to do physical activities.
RECOVER-ENERGIZE Post-Exertional Malaise (Structured Pacing): a program for participants with PEM designed to help them get to know, control, and minimize PEM symptoms to stabilize their daily functioning and improve their quality of life.
Participants with PEM will NOT be included in study activities that involve exercise to minimize the risk of their PEM getting worse.

Inclusion

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. ≥ 18 years of age at the time of enrollment

2. Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization16? ? Suspected or probable SARS-CoV-2 infection will only be allowed if it occurred before May 1, 2021, and will be limited to no more than 10% of the study population. Otherwise, confirmed cases are required. Refer to the Manual of Procedures (MOP) for details. Suspected case of SARS-CoV-2 infection - Three options, A through C: A. A person who meets the clinical OR epidemiological criteria. Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization; or C. With no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test. Probable case of SARS-CoV-2 infection: A. A patient who meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster. Confirmed case of SARS-CoV-2 infection - Two options, A and B: A. A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or B. Meeting clinical criteria AND/OR epidemiological criteria (See suspected case A above for criteria). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test. 

3. Self-reported limitation to physical activity due to the presence of symptoms such as fatigue, shortness of breath, and/or PEM following a SARS-CoV-2 infection, that has persisted for at least 12 weeks and is present at the time of consent.

4. Willing, able, and agree to provide informed consent, complete questionnaires and outcome assessments, and participate in the study, including assigned intervention or control and study visits whether remote, hybrid, or in-person.

Exclusion

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Known active acute SARS-CoV-2 infection ≤ 4 weeks prior to the consent.

2. Known prior diagnosis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), not related to SARS-CoV-2 infection.

3. Current or recent use (within the last 14 days) of a formal program utilizing one or more of the current study intervention(s) or similar intervention(s) to treat the underlying condition, unless a washout period is permitted per Appendices.

4. Participation in another interventional clinical trial.

5. Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study.