Long Haul COVID Rehabilitation & Recovery Research Program

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the physiologic, immunologic, and mental health effects of a rehabilitation program on patients with Long Haul COVID (LHC).

Detailed Description
-----------------
1.0 Objectives 1.1 Describe the purpose, specific aims, or objectives. The purpose is to assess the physiologic, immunologic, and mental health effects of a rehabilitation program on patients with Long Haul COVID (LHC). 1.2 State the hypotheses to be tested. Long Haul COVID Patients who enroll and complete a 10 week program of Physiologic and Psychological Rehabilitation will have reduced Long Haul COVID Symptoms, Improved Physical Status, Reduced Inflammatory Markers, and Augmented Psychological Well Being.

Official Title
-----------------
Long Haul COVID Rehabilitation Research Program

Conditions
-----------------
Long Haul COVID or Post Acute Sequella of COVID - PASC (U09.9)

Intervention / Treatment
-----------------
* Other: Virtual vs On Site Pulmonary Rehabilitation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Long Haul COVID Infection (Documented by PCR or patient report) Age >= 18 years old. At least 12 weeks since the initial COVID Infection. One or more of the following symptom/signs: Fatigue, Dyspnea, Exercise Intolerance, Post Exertional Malaise and/or Difficulty Breathing. Able to perform a cardiopulmonary exercise test. Exclusion Criteria: Patients is not able to perform technically acceptable pulmonary function tests and symptom-limited cardiopulmonary cycle ergometry tests. Patients who desaturate to SpO2 <80% on screening incremental exercise testing. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit or patients who are currently in a pulmonary rehabilitation program. Patients who have taken an investigational drug within one month or six half-lives (whichever is greater) prior to screening visit (Visit 1). Pregnant or nursing women. Women of childbearing potential who are not using a highly effective method of birth control. Female patients will be considered of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years. Patients who are currently participating in another interventional study. Malignancy for which the patient has undergone resection, radiation therapy, or chemotherapy within the last 2 years Any other significant disease than COVID which, in the opinion of the investigator, may i) put the patient at risk because of participation in the study, ii) influence the results of the study (e.g. Insulin or testosterone therapy, systemic corticosteroids, HIV, etc), iii) cause concern regarding the patient's ability to participate in the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups: Post exertional Malaise (PEM) present who will receive virtual low intensity rehabilitation. No Post Exertional Malaise group (no PEM) who will receive 10 weeks of traditional pulmonary rehabiltiation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: + PEM<br>Patients who experience Post Exertional Malaise (PEM) will receive 10 weeks of virtual rehabilitation. | Other: Virtual vs On Site Pulmonary Rehabilitation<br>* As part of the on site or virtual visits, the subject will receive standard pulmonary rehabilitation educational instruction on balance and strength training, stretching, nutrition, hydration, pacing, proper breathing, small or mini-lectures, and information on relaxation techniques. If post exertional malaise is present, the patient will only receive the educational sessions, no aerobic training.<br>|
| Experimental: No PEM<br>Patients who do not experience Post Exertional Malaise (PEM) will receive 10 weeks of traditional pulmonary rehabilitation. | Other: Virtual vs On Site Pulmonary Rehabilitation<br>* As part of the on site or virtual visits, the subject will receive standard pulmonary rehabilitation educational instruction on balance and strength training, stretching, nutrition, hydration, pacing, proper breathing, small or mini-lectures, and information on relaxation techniques. If post exertional malaise is present, the patient will only receive the educational sessions, no aerobic training.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in aerobic capacity (Peak Oxygen Uptake, Anaerobic Threshold and Maximum Work rate) at 10 weeks after a comprehensive (normal intensity) pulmonary rehabilitation program. | Exercise, Immunologic, and Neuropsychiatric Outcomes. | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in General Quality of Life | SF-36 | 10 weeks | 
| Change in a Fatigue Score | Fatigue Severity Score questionnaire | 10 weeks | 
| Change in Anxiety scores | General Anxiety Disorder Screener (GAD-7) | 10 weeks | 
| Change in the Inflammatory Cytokines . | CRP, Ferritin, D-Dimer, IL-6, IL-10, IL2, TNF-alpha, and INF-gamma | 10 weeks | 
| Change in Sleep Quality Index | Pittsburg Sleep Quality Score (PSQI) | 10 weeks | 
| Change in a Dyspnea score. | Modified Medical Research Council Dyspnea Scale (mMRC) | 10 weeks | 
| Change in a Post Exertional Malaise score. | Modified DePaul Assessment for Post-Exertional Malaise | 10 weeks | 
| Change in Depression scores | Patient Health Questionnaire (PHQ-9) | 10 weeks |