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Enhanced External Counterpulsation for Post-Acute Sequelae of COVID-19 (PASC), Long COVID

Long COVID goes by many names, including post-COVID symptoms (PCS), post-acute sequelae of SARS-CoV-2 infection (PASC), and post-acute COVID syndrome (PACS).  The preceding terms refer to a condition in which patients experience new, returning, or lingering symptoms 12 weeks after initial COVID infection.  These symptoms may persist for weeks, months, or sometimes even years after the acute infection phase.  Long COVID is estimated to occur in as many as 57% of patients who contract the virus in any of its forms, including Omicron. 


There are over 200 symptoms associated with long COVID, some occurring with much greater frequency than others.  The Centers for Disease Control (CDC), which regularly updates its long COVID data, currently lists the following symptoms among those most commonly associated with long-COVID:


General Symptoms

  • Tiredness or fatigue that interferes with daily life

  • Symptoms that get worse after physical or mental effort (also known as “post-exertional malaise”)

  • Fever

Respiratory and Heart Symptoms

  • Difficulty breathing or shortness of breath

  • Cough

  • Chest pain

  • Fast-beating or pounding heart (also known as heart palpitations)

Neurological Symptoms

  • Difficulty thinking or concentrating (sometimes referred to as “brain fog”)

  • Headache

  • Sleep problems

  • Dizziness when you stand up (lightheadedness)

  • Pins-and-needles feelings

  • Change in smell or taste

  • Depression or anxiety

Digestive Symptoms

  • Diarrhea

  • Stomach pain

Other Symptoms

  • Joint or muscle pain

  • Rash

  • Changes in menstrual cycles

While COVID-19 is generally regarded as a respiratory disease, it is now clear that cardiovascular issues rank among the most prevalent of post-COVID symptoms.  A paper published in JAMA Cardiology found a startlingly high frequency (~60%) of post-viral or inflammatory myocarditis (inflammation of the heart) in people who have had COVID-19.


"Taken together, we demonstrate cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%) with recent COVID-19 illness, independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19."


As the above excerpt from the article indicates, long COVID symptoms can develop in anyone who is exposed to the virus, regardless of the severity of their initial infection.  This means that a patient who tests positive but has only mild symptoms (or even no symptoms at all) may develop severe long COVID symptoms, while a patient who required hospitalization from COVID may make a full recovery and have no lingering symptoms.  Long COVID is unpredictable in this way, and it is too early for us to understand why some COVID survivors develop it and some do not.  It occurs in both males and females of all ages, with fatigue being the most common symptom for women, and breathing difficulties being the primary symptom for men, according to a recent Mayo Clinic article. 


Long COVID symptoms can vary in severity, from mild to debilitating.  While some patients may experience only occasional fatigue, others may be unable to get out of bed.  There is anecdotal evidence that suggests that most long COVID symptoms improve over time, but it is too soon to gauge long-term outcomes for long COVID patients.  

The causes of long COVID are not completely understood; however there are three prevalent theories at this time, each with mounting, supportive scientific data, as detailed below.

Perceived Causes of Long COVID

Persistent Inflammation

Some symptoms of long COVID occur across multiple organ systems, and are believed to be the cause of  proteins triggering the release of inflammatory cytokines.

Endothelial Damage

Persistent immune activation in response to COVID-19 infection is posited to lead to endothelial dysfunction, resulting in some of the symptoms (including chest pain) associated with long COVID.

Autonomic Dysregulation

Some long COVID symptoms (dizziness, "brain fog," are believed to be the result of orthostatis syndromes triggered by immune-mediated disruption of the autonomic nervous system.

Role of Inflammation in Symptomatic Long COVID

Some long COVID symptoms are believed to be the result of inflammation that begins shortly after a person is first exposed to the virus.  COVID-19 is known to produce an inflammatory response in the body by infecting immune cells called monocytes in the blood, and macrophages in the lungs. This infection causes the immune cells to experience a form of cell death known as pyroptosis, which releases inflammatory cytokines (small proteins that control cell growth and other cellular activity).  This causes fever and summons more immune cells to the site.  While the purpose of this process is to fight infection, older people and people with underlying health conditions (diabetes, obesity, etc.) are more likely to become severely ill with COVID, since those conditions already involve inflammation.

A research team at Massachusetts General Hospital compared blood samples from COVID patients with samples from healthy people and patients with other respiratory illnesses. They also looked at lung autopsy tissue from COVID fatalities.  All the patients had signs of respiratory distress, but COVID patients had more dying cells.  About 6% of blood monocytes found in infected COVID patients died a pyroptotic (inflammatory) death, as did about a quarter of macrophages from the lung tissue.


It is presumed that COVID survivors who go on to develop long COVID may have lingering inflammatory cytokines in their bodies.  These inflammatory proteins roam freely throughout the body and have the potential to affect multiple systems, which offers one explanation for the long list of potential long COVID symptoms a patient may experience.  The most severe manifestation of this phenomenon is Multisystem Inflammatory Syndrome (MIS, MIS-C [children], MIS-A [adult]), a rare condition in which, as the name implies, widespread inflammation occurs throughout the body as a result of COVID-19 infection, occurring 2-12 weeks after exposure to the virus.  MIS, along with the so-called “cytokine storm” associated with COVID-19 fatalities, represents an exaggerated, hyper-inflammatory immune response to the virus.  

Nonetheless, as previously stated, there does not appear to be any link between the severity of initial infection and the development of long COVID symptoms.  Patients with severe inflammatory responses leading to hospitalization during the acute infection phase of COVID-19 are not at higher risk of developing long COVID.  Likewise, an asymptomatic acute infection phase does not predict a lower likelihood of developing long COVID.

Role of Endothelium in Post COVID Symptoms

Another prevailing theory related to the development of long COVID is centered on dysfunction caused to the endothelium as a result of COVID infection.  This is a highly complex topic, but in short, COVID-19 is known to affect microcirculation, causing endothelial cell swelling and damage (endotheliitis), microscopic blood clots (microthrombosis), capillary congestion, and damage to pericytes that are integral to capillary integrity and barrier function, tissue repair (angiogenesis), and scar formation. These effects predictably translate to problems in multiple organ systems, including the brain, heart, kidneys, liver, skeletal muscle, and skin of infected patients.

Role of Autonomic Dysfunction in Post COVID Symptoms

A growing number of COVID-19 survivors develop conditions of orthostatic intolerance, including postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), and  vasovagal syncope (VVS).  While the reasons for this are not yet clear, there are known mechanistic associations between some autonomic disorders (including POTS and OH) and autoantibodies.  Other posited explanations for COVID-induced dysautonomia include  deconditioning (from prolonged bedrest during acute infection), hypovolaemia (low extracellular fluid volume) and/or immune- or virus-mediated neuropathy


Our Treatment Rationale

The P-CCCOC approach to treating long COVID conditions with EECP can be separated into two groups: empirical and theoretical—that is, what has been clinically observed, and what is suspected based on informed medical opinion.  

What is Known (Empirical Evidence Supporting EECP in the Treatment of Long COVID Symptoms)

Owing to the novelty of the COVID-19 virus and the relative obscurity of EECP therapy, only a small number of studies directly testing EECP’s efficacy in treating long COVID symptoms exist.  Here is what is scientifically proven to be the case:


  • EECP can significantly reduce the symptoms of postural orthostatic tachycardia syndrome (POTS), including brain fog, fatigue, chest pain, exercise intolerance, and fainting.

  • EECP provides equivalent benefits to light cardiovascular exercise, rendering it a viable mechanism for rehabilitating long COVID patients whose present conditions preclude them engaging in the traditional forms of physical therapy (stationary bike, treadmill).

What is Postulated (Medically-Informed Theories as to the Possible Benefits of EECP in the Treatment of Long COVID Symptoms)

Our theories supporting EECP as a possible treatment modality for long COVID are based on three proposals.  


  • Because some of the most common long COVID symptoms mirror symptoms that EECP is proven to improve (chest pain, shortness of breath, fatigue), EECP may benefit some patients suffering from long COVID conditions.

  • Because there is mounting evidence that some long COVID symptoms are related to COVID-induced endothelial dysautonomia, and EECP is known to improve endothelial function, it is possible that some long COVID patients may benefit from EECP treatment.

  • Because there is evidence linking some long COVID symptoms to the persistent presence of inflammatory cytokines in the body after COVID-19 infection, and EECP is known to stimulate a powerful anti-inflammatory response in the body, it is possible that some long COVID patients may benefit from EECP treatment.


EECP Versus Pharmaceuticals and Physical Therapy in the Treatment of Long COVID

Recently (in 2022 in particular) a number of Post-COVID clinics have emerged globally, the aim of which is to provide help to patients whose lives have suffered long-term impacts from COVID-19 infection.  Typically these clinics act as multidisciplinary hubs—that is, they have providers on staff who assess long COVID patients’ conditions and then refer them to specialists as needed.  For example, if a patient complains of respiratory difficulties and heart palpitations, he/she may be sent to a pulmonologist and cardiologist respectively.  Each specialist will then attempt, generally through the use of medications, to treat the patient’s symptoms.  If a patient is suffering from a large number of different symptoms, he/she is then likely to be prescribed a large number of medications, each with potential side-effects.  For long COVID patients suffering from reduced exercise capacity, shortness of breath, and fatigue, post-COVID clinics typically prescribe physical therapy, which can be very difficult for patients to begin, given their limitations. 


The P-CCCOC approach is different.  In lieu of pharmaceutical and rigorous physical therapy interventions, we prescribe EECP for the following reasons:


  1. EECP is a safe and well-tolerated treatment with no clinically significant side-effects.


This may be of particular importance to patients experiencing one of the more complex long COVID, such as POTS.  In most cases, medications must be prescribed to treat individual symptoms of POTS, and may include combinations of the following:

  • Antidepressants: Bupropion (Wellbutrin), Paroxetine (Paxil), or Sertraline (Zoloft)

  • Antidiuretics: DDAVP (Desmopressin acetate)

  • Beta Blockers: Propranolol (Inderal)

  • Centrally acting sympatholytic drugs: Clonidine (Catapres)

  • Cholinesterase Inhibitors: Pyridostigmine Bromide (Mestinon)

  • Mineralocorticoids: Fludrocortisone (Florinef)

  • Stimulants: Amphetamine and Dextroamphetamine (Adderall), Methylphenidate (Concerta)

  • Modafinil (Provigil)

  • Vasoconstrictors: Midodrine (ProAmatine)


This represents a grim reality for patients who may have been otherwise healthy before COVID infection.  EECP offers a clinically-proven alternative to the above medications with no risk of significant side-effects.  


2. EECP provides “passive exercise, and makes minimal physical demands on patients.  


  1. This is significant, as fatigue, dyspnea (labored breathing), and anxiety are common Long COVID symptoms and contribute to a weariness to attend strenuous physical therapy sessions.  (It is for this reason that some post-COVID programs offer virtual visits that allow patients to receive [limited] care from the comfort of their homes.)  The passive exercise effect of EECP may help to rehabilitate extremely debilitated patients to a point of once again being able to engage in physical activity.


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