The COVID-19 pandemic severely impacted the medical system both directly but also throughincomplete recovery from the virus in the form of post-acute sequelae of COVID-19 (PASC).PASC affects at least 9.6 million individuals as of May 2022 and continues to affect manymore. PASC is a multisystem disorder often presenting with mental fog, dyspnea onexertion, and fatigue among other symptoms. The etiology of PASC is uncertain buttheories include direct cytotoxicity, dysregulated immune responses, endotheliitisassociated with microthrombi, eNOS uncoupling, and myocardial fibrosis with impairedventricular compliance. To date, there are no established treatments. Exercise has thepotential as a therapeutic option to improve VO2peak and improve each of theaforementioned underlying etiologies. The investigators plan to examine the effect ofHigh-Intensity Interval Training (HIIT) and Moderate intensity exercise training (MOD) onthe symptoms and exercise tolerance of patients with PASC.The investigators approach will consist of a randomized, blinded, 2-arm, parallel-groupdesign. Enrolled subjects will be randomly assigned to one of two groups in a 1:1allocation ratio. All groups will undergo a 4-week intervention of 3 days of HIIT perweek and 2 days of MOD per week or control of light stretching and controlled breathing.Subjects will be assessed before and after the 4-week intervention to examine the extentto which 4 weeks of the HIIT and MOD combination improves VO2peak and left ventriculardiastolic function, global longitudinal strain (GLS), and global circumferential strain(GCS). Further, the investigators will explore changes in markers such as heart rate,heart rhythm, blood pressure, quality of life, exercise tolerance, and PASC symptoms aswell as blood/serum markers.
Not Provided
Behavioral: Exercise
Patients will perform 5 days of supervised stationary cycling exercise (with EKG
telemetry) per week over a period of 4 weeks. Training heart rates will be determined
based on the pre-testing VO2peak and peak heart rate (PHR).
- Of the 5 sessions, 3 will be HIIT sessions and 2 will be MOD sessions.
- Subjects exercising on the HIIT day will start with eight intervals of 2-min
duration at 80-85% of PHR, separated by 2 min of recovery at 50% of PHR, progressing
to four, 4-min intervals at 90-95% PHR, separated by 3 min at 50% PHR by the end of
week 2.
- Subjects exercising on the MOD days will perform uninterrupted for 40 minutes
duration at 60-65% of PHR progressing to 40 minutes duration at 70-75% of PHR by the
end of week 2.
- Each training session will begin with a 10-min warm-up at 50% PHR and end with a
5-min cool down at 50% PHR. Exercise progression may have to be modified according
to individual subject exercise tolerance.
Inclusion Criteria:
- 18-50 years of age
- Diagnosed with Post Acute Sequelae of COVID-19
- Physician clearance to undergo exercise training (see section titled
cardiorespiratory fitness testing for details; page 6)
- Complete COVID-19 vaccination status
Exclusion Criteria:
- Unstable angina or myocardial infarction in the past 4 weeks
- Uncompensated heart failure
- NYHA class IV symptoms
- Complex ventricular arrhythmias
- Musculoskeletal contraindications to stationary bicycling exercise
- Symptomatic severe aortic stenosis
- Acute pulmonary embolus
- Acute myocarditis
- Uncontrolled Hypertension as defined as systolic blood pressure > 180 mm Hg or
diastolic blood pressure > 120 mm Hg
- Medication non-compliance
- Pregnant women-self reported
- COPD GOLD stage D
- Malignancy currently actively being treated
- Uncontrolled Asthma
- Uncompensated Cirrhosis of the Liver
- Chronic Kidney disease requiring dialysis therapy
- Symptomatic Anemia
- Hemoglobin <7g/dL
- Poorly controlled diabetes or A1c>9%
- BMI >35kg/m2
- Pulmonary Hypertension stage IV
- Any condition requiring supplemental oxygen
- Multiple Sclerosis
University of Virginia University Hospital
Charlottesville 4752031, Virginia 6254928, United States
Siddhartha S Angadi, PhD, Principal Investigator
University of Virginia