Enhanced External Counterpulsation to Treat Long COVID-19 Fatigue

Enhanced External Counterpulsation (EECP/ECPT) to Treat Long-COVID-19 Fatigue - a Randomized Controlled Trial

The goal of this double blind, outcome-assessor blind, randomized controlled trial, is to compare the effectiveness of external encounter counterpulsation (EECP) versus sham procedure in participants with long COVID-19 fatigue.

The main question[s] it aims to answer are:

• Whether EECP improves fatigue score
• Whether EECP improves quality of life, six-minute walk test, and endothelial function Participants will attend 15 sessions (1-hour each) of EECP during 5 weeks Researchers will compare EECP versus sham procedure for the above outcomes.

Participants of this trial will be patients recovering from acute COVID-19, 3-12 months following the acute infection, and suffering from fatigue with a Patient-Reported Outcomes Measurement System (PROMIS)-Fatigue short-form (SF)-7a score of > 50.

Exclusion criteria will include contra-indications for EECP (see protocl). Intervention, comparisn and outcomes are described above. Study plan: participants will be invited using social media, after filling a fatigue score (PROMIS) to test for eligibility. Those with a score of > 50 will be invited for a study visit.

Study visit 1 will include informed consent, followed by physician interview, physical examination, ECG; and will be referred for completion of blood tests including complete blood count (CBC) to rule out significant anemia (Hb< 12 for men or hb <10 for women) and serum beta human chorionic gonadotrophin (bHCG).

Eligible patients will then be randomized into two groups for treatment with EECP vs sham procedure. In study Visit 2 they will answer several questionnaires, perforn EndoPAT test to assess endothelial dysfunction, and six-minute walk test, followed by either:

1. Treatment group- 1 hour EECP session
2. Sham group - 1 hour of a sham EECP session (patients will be hooked to the EECP device but it will be set to the lowest setting, and lowest frequency, therefore unable to create a sufficient rise in diastolic return). This visit will be followed by 3 times weekly 1 hour sessions for 5 weeks (15 sessions) of either EECP or sham procdeure, according to randomization group.

Questionnaire that will be used before and after the intervention will include:

1. Fatigue evaluation using the PROMIS 7a form, attached in appendix (as validated on Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)patients)
2. Functional capacity evaluation using the Duke Activity Status Assessment (DASI) (https://www.mdcalc.com/duke-activity-status-index-dasi);
3. Shortness of Breath using the modified Medical Research Council dyspnea scale
4. Quality of life using the SF-36 questionnaire. 6mwt and endothelial dysfunction by EndoPAT will be held following the last treatment.

Study Visit 3 (3 months following starting treatment) will be a final Interview to assess improvement by questionnaires, as well as time to return to activity and time to return to work.

Inclusion Criteria:

• Patients recovering from PCR or lateral flow testing proven acute COVID-19
• 3-12 months following the acute infection
• Suffering from fatigue with a PROMIS-SF-7a T-score of > 50

Exclusion Criteria:

• Acute decompensated heart failure
• Recent myocardial infarction within the last 3 months
• Unstable angina pectoris
• Severe hypertension > 180/110 mm Hg
• Coagulopathy with international normalized ratio of prothrombin time > 2.0
• Moderate to severe aortic regurgitation
• Abdominal aortic aneurysm (>5 mm) or dissection
• Arrhythmias that may interfere with triggering of EECP system (uncontrolled atrial fibrillation, flutter and very frequent premature ventricular contractions)
• Heart rate of <35 or >125 beats per minute
• Any surgical intervention within 6 weeks before EECP
• Recent cardiac catheterization (1-2 weeks) or arterial femoral puncture
• Severe peripheral arterial disease
• Severe venous disease (thrombophlebitis, prior or current deep vein thrombosis or pulmonary embolism)
• Severe chronic obstructive pulmonary disease
• Pregnancy or women of childbearing age who do not have a negative pregnancy test