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ME/CFS (Chronic Fatigue Syndrome), Long Covid and Your Health

Sep 24th 2020 | By Irina Rozenfeld DNP, APRN, ANP-BC

She is preparing for exams

Conventional medicine has historically overlooked patients with ME /CFS (Myalgic Encephalomyelitis / Chronic Fatigue Syndrome) and people have often spent years without a definite diagnosis. CDC data shows that more than 80% of patients are not diagnosed; for 75% of patients it takes more than a year to get a diagnosis, and 30% spent more than five years to get a diagnosis. Less than 40% of medical textbooks have information about ME/CFS and only 1/3 of medical schools include ME/CFS topic in the curriculum.1

Such a complex condition as ME/CFS requires a personalized approach to eliminate other possible causes, diagnose all comorbidities, and develop a personalized treatment plan together with the patient and the patient’s family. All of us at Rezilir Health are happy to listen and help those with ME/CFS. We are trained to implement pharmacological and non-pharmacological modalities to treat and control symptoms and improve each patient’s quality of life.

The response to the patients’ complaints from healthcare providers often sounds like “there is nothing wrong with you.” This could be not be further from the truth. A renowned specialist in ME/CFS Dr. Nancy Klimas compared patients’ suffering as “…they experience a level of disability equal to that of patients with late-stage AIDS and patients undergoing chemotherapy”2. This has been a significant tragedy in conventional medicine because many patients have had significant disability, but the conventional system has not responded appropriately to their needs. Unfortunately, it has been historically overlooked by conventional medicine.

Diagnostic Criteria

One underlying reason that conventional medicine has overlooked ME/CFS may be that routine laboratory tests are usually normal.  Dr. Anthony Komaroff, a prominent physician studying ME/CFS, points that those standard tests are the wrong tests to measure this illness.3 More advanced testing such as testing for orthostatic intolerance can bring out objective biomarkers that can be followed.  In 2015, the National Academy of Medicine (NAM)4 established new evidence-based clinical criteria describing distinctive ME/CFS symptoms to use for diagnosing patient with ME/CFS (SEID). Another new name for ME/CFS- SEID is Systemic Exertion Intolerance Disease.

The diagnosis requires that the patient have the following three symptoms:

  1. A substantial reduction or impairment in the ability to engage in pre-illness levels of occupational, educational, social, or personal activities, that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest.
  2. Post-exertional malaise
  3. Unrefreshing sleep

At least one of the two following manifestations is also required:

  1. Cognitive impairment
  2. Orthostatic intolerance

The NAM (2015) report also underscores three symptom manifestations of ME/CFS (SEID):  Pain, immune impairment, and infection.

  1. Pain is common in ME/CFS (SEID) and can come in many forms, including headaches, arthralgia, and myalgia.
  2. Immune impairment data shown poor NK cell cytotoxicity (NK cell function, not number) that correlates with illness severity in ME/CFS (SEID) patients and could serve as a biomarker for the severity of the disease.
  3. The ME/CFS (SEID) can follow infection with Epstein Bar virus and possibly other specific infections, but there is insufficient evidence to conclude that all cases of ME/CFS are caused by EBV or that ME/CFS (SEID) is sustained by ongoing EBV infection. 

The underlying complex pathophysiologic mechanisms of ME/CFS remain poorly understood, and diagnostic process is reliant on the process of elimination due to the lack of a single, clear set of diagnostic markers. Nevertheless, strong epidemiologic, clinical, and basic science studies have demonstrated neurologic, immunologic, hormonal, and gastrointestinal components to the condition.

ME/CFS has been shown to be triggered by infection, viral or bacterial (e.g., Epstein-Barr virus, Mycoplasma pneumonia, Giardia duodenales, Coxsackie B virus, Human herpesvirus 6 and 7, Q fever, Parvovirus B 19), and progression of disease associated with immune dysregulation such as IgG subclass deficiency, low Natural Killer (NK) cells cytotoxicity, abnormal antiviral response, T-helper 2 cellular immunity dominance and activation of proinflammatory cytokines in response to exercise5,6. A patient may present with endocrine abnormalities and autonomic dysfunction contributing to sympathetic nervous system overdrive and destabilization of the neuroendocrine system.

Genetic pre-disposition has been described, with female gender being a risk factor. ME/CFS may overlap with mast cell activation syndrome, orthostatic intolerance, POTS, Ehlers Danlos syndrome, multiple chemical sensitivities, hypovolemia, small fiber neuropathy, and a history of hazardous environmental exposure. ME/CFS has strong associations with fibromyalgia as well as autoimmune conditions such as Sjogren’s syndrome, or autoimmune autonomic dysfunction. Many patients with ME/CFS also commonly complain of gastrointestinal (G.I.) symptoms and have functional G.I. dysfunction, irritable bowel syndrome (IBS), celiac disease, and food intolerance as a cause of nutritional imbalance. Recently, autoantibodies against neurotransmitter receptors were identified in ME/CFS and POTS. Substantial research evidence is also emerging supporting mitochondrial and metabolomics dysfunction in ME/CFS7.

Timely Recognition and Appropriate Treatment Can Significantly Improve Patient Functional Status

CFS and aging

Upon diagnosis, the treatment of ME/CFS relies on managing symptoms and improving the quality of life by understanding the main underlying mechanisms of disease onset, activity, and progression. Sometimes it is very difficult to differentiate ME/CFS from other conditions. Diagnosing ME/CFS can be challenging and relies on a combination of detailed history, physical exam, and diagnostic tests.

  • Medical history. Collection of patient’s medical and life history from personal interaction and review of medical records requires a substantial amount of time but is a vital for building a correct diagnosis and development of therapeutic relationships between patient and clinician. I request the patient write down their medical history, all questions that need to be addressed and bring it with them for the first visit.
  • Fatigue. Fatigue in ME/CFS is a major pathological symptom. Assessment and monitoring the ranges of fatigue may require completion of questionnaires, activity logs, or wearing measurement devices to create a personalized energy conservation plan.
  • Cognitive dysfunction. Cognitive dysfunction and neurologic symptoms often called “brain fog” are the most debilitating symptoms in ME/CFS. Prompt assessment should start with neurocognitive testing followed, if necessary, by imaging studies and/or neurotransmitters and hormone levels evaluation.
  • Laboratory investigation. While we use routine laboratory testing to rule out the treatable chronic diseases with symptoms similar to ME/CFS, we also employ numerous specific laboratory tests to identify pathways causing neuroinflammation, autoimmunity, and multiple infections. The immunologic panels allow to evaluate immune dysregulation state in ME/CFS possibly provoked by chronic infection, inflammation, or environmental exposure.
  • Sleep. Patient with ME/CFS have non-restorative sleep and usually feel tired in the morning. While it is important to evaluate sleep hygiene, and circadian rhythm, formal polysomnography and a sleep specialist evaluation is necessary in some cases to develop a sound treatment plan. 
  • Post exertional malaise (PEM). PEM is a major symptom in ME/CFS representing severe deterioration of patient functioning after physical or cognitive activity. The impaired aerobic metabolism is responsible for pathological fatigue and prolonged recovery time in ME/CFS. A Cardiopulmonary test (CPET) can be used to assess exercise capacity (maximal oxygen consumption/VO2max) to provide objective measurement of severity and duration of patient’s PEM, impaired cognitive function, and fatigue.
  • Pain.The treatment for pain in ME/CFS varies depending on severity level, presence of comorbid conditions, and is addressed with many useful pharmacological and non-pharmacological modalities.
  • Environmental sensitivities/multiple chemical sensitivities. Patients with ME/CFS can have multiple allergies as well as develop sensitivities to odors, foods, and even electromagnetic fields. Environmental history assessment in conjunction with professional home evaluation may help to identify and avoid possible triggers.
  • Orthostatic intolerance (OI). While OI is one of the frequent symptoms in a number of illnesses, careful diagnostic evaluation on a patient with ME/CFS and OI may help to establish appropriate pharmacological regimen, initiate referral to a specialist, and add non-pharmaceutical methods to completely control these symptoms.
  • Nutrition. Physical fatigue and post-exertional malaise (PEM) in patients with ME/CFS can be explained by abnormal energy metabolism 7,8potentially associated with irregular nutritional status.9 In a 2010 Canadian Community Health Survey, 20 percent of patients with ME/CFS were described as not having adequate access to healthy foods.5 My research allowed me to identify that 85 percent of patients in my study sample had a moderate or high risk for nutritional deficiency. While clinical trials to date have yet to correlate nutritional status with ME/CFS symptomatology consistently, some parallels have been made. Research and anecdotal data demonstrated the beneficial effects of nutraceutical supplements on symptoms’ severity in ME/CFS and fibromyalgia. Understanding dietary deficiencies in any chronic inflammatory condition can help clinicians diagnose weaknesses and address them individually.


CFS Covid

The COVID-19 pandemic is causing global attention to fatigue that occurs after viral illnesses. Patients recovering from COVID-19 are reporting unresolved symptoms characteristic of ME/CFS and are calling themselves “long haulers.” 10 This attention to ME is long overdue as it has been a poorly recognized but common issue. ME/CFS affects an estimated 836,000 to 2.5 million Americans. According to the U.S. Clinician Coalition, a group of clinician experts in ME/CFS, an estimated 84 to 91 percent of patients have not yet been diagnosed. ME/CFS affects 3 times as many women as men and reported in patients younger than age 10 and older than age 70. The onset of the illness peaks between age 11-19 and 30-39 years old. At least 25% of patients are bedbound or housebound and up to 75% are unable to work or attend school. Symptoms can persist for years, and patients may never regain their pre-disease functioning. ME/CFS costs the US $17 to $24 billion annually in lost productivity and direct medical costs.11

The first time someone may become concerned with ME/CFS is when they notice extreme fatigue and malaise after any physical or mental activity, even after their routine exercise. An individual can also notice that recovery after any exertion takes longer, and night sleep does not provide the usual refreshment, or there is significant difficulty falling asleep. The persistent or relapsing debilitating fatigue and post exertional malaise in ME/CFS usually do not resolve with rest and is severe enough to impair everyday daily activity in comparison to the individual’s pre-illness activity level. Frequently, a patient may remember the episode of infectious illness, such as mononucleosis or flu (or now potentially COVID-19), from which they “have never recovered.” The onset of ME/CFS is often abrupt. Moderate to severe fatigue which is present at least 50% of the time is a key finding distinguishing ME/CFS from other causes of chronic fatigue.

If you or someone you know is currently suffering from symptoms of ME/CFS and are frustrated with your current care and have been told “there is nothing wrong with you,” at Rezilir, we will listen to your story.

In addition, for more information or to schedule your appointment, please use the REQUEST APPOINTMENT form.


  1. Bateman, L. (2018). Myalgic Encephalomyelitis/Chronic fatigue Syndrome: Updates and management tips for clinicians.

2. University of Miami ME/CFS Researcher Nancy Klimas, MD, Explains the Complexity of Chronic Fatigue Syndrome in Terms That Anybody Can Understand. (January 11, 2008).

3. Komaroff AL. Advances in Understanding the Pathophysiology of Chronic Fatigue Syndrome. JAMA. 2019;322(6):499–500. doi:10.1001/jama.2019.8312

4. National Academy of Sciences. (2015). Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Retrieved from

5. Bested, A.C. & Marshall, L. M. (2015). Review of Myalgic encephalomyelitis/Chronic Fatigue Syndrome: An evidence-based approach to diagnosis and management by clinicians. Reviews on Environmental Health, 30, 223-49, Link Removed

6. Baraniuk, J. (2019). Chronic fatigue syndrome/Myalgic encephalomyelitis. Retrieved from

7. Naviaux, R. K., Naviaux, J.C., Li, K., Bright, A. T., Alaynick, W. A., Wang, L., … Gordon, E. (2016). Metabolic features of chronic fatigue syndrome. Proceedings of the National Academy of Sciences of the United States of America 113, E5472– E5480,

8. Armstrong, C. W., McGregor, N. R., Lewis, D. P., Butt, H. L., & Gooley, P. R. (2015). Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients. Metabolomics, 11, 1626-1639. doi:10.1007/s11306-015-0816-5

9. Campagnolo, N., Johnston, S., Collatz, A., Staines, D. & Marshall-Gradisnik, S. (2017).  Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: A systematic review. Journal of Human Nutrition and Diet, 30, 247-259.

10. NIH Director’s Blog. (September3, 2020). COVID-19 long haulers.

11. U.S. ME/CFS Clinician Coalition (2020). Diagnosing and treating myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

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