Understanding ME/CFS and Long COVID as Post-Viral Conditions
By Susan Carr, Senior Writer
The experience of patients whose COVID-19 symptoms persist for four weeks or more—Long COVID or post-COVID syndrome—has led to renewed interest in myalgic encephalomyelitis/chronic fatigue syndrome (MF/CFS), an illness with symptoms similar to Long COVID. Both conditions involve uncertainty regarding diagnosis, treatment, and prognosis and are subject to ongoing research. Organizations worldwide, including the National Institutes of Health in the United States, are exploring the possible connections between Long COVID, ME/CFS, and other similar conditions.
To better understand ME/CFS and its connection to Long COVID, Susan Carr, Senior Writer for ImproveDx, recently talked with Jaime Seltzer. In a plenary session at the 14th annual Diagnostic Error in Medicine conference, Seltzer explored the similarities and differences between Long COVID, ME/CFS, and other conditions that a viral infection may trigger. Seltzer, diagnosed with ME/CFS in 2015, is Director of Scientific and Medical Outreach at #MEAction, an international nonprofit focused on education, research, and advocacy for people with ME/CFS. She also consults on several research projects at Stanford University, including some with Professor Ronald Davis, PhD, director of the Stanford Genome Technology Center and ME/CFS researcher, whose son, Whitney, is severely ill with ME/CFS.
Perhaps as many as 2 million or more Americans have ME/CFS, although most of them have not been diagnosed, according to a report published by the Institute of Medicine (IOM) in 2015. The IOM undertook the report to reevaluate diagnostic criteria for ME/CFS and develop a process for updating those criteria based on new research.
Patients and clinicians will benefit from an increased understanding of ME/CFS and Long COVID and the relationship between the two illnesses, which are considered in many cases to be post-viral conditions triggered by infection. In the 2015 report, the IOM proposed a shortlist of symptoms that indicate a diagnosis of ME/CFS (see sidebar). Those symptoms are similar but not identical to symptoms of Long COVID. Clinicians and researchers point out that listening carefully to patients and distinct discerning symptoms are important to identify COVID patients who have developed ME/CFS. In addition to physicians and other clinical researchers, patients, and advocacy organizations actively seek effective treatments for both conditions. They have found that recognizing and treating them promptly can be advantageous.
Susan Carr: I’ve read that pre-COVID-19, you and some of your Stanford colleagues thought that it might take a pandemic for the scientific community to take myalgic encephalomyelitis/chronic fatigue syndrome seriously. Please explain the connection.
Jaime Seltzer: Yes, that hypothesis about a pandemic was mentioned in a Time magazine article published in October 2020. Having had difficulty gaining adequate support for our work, we wondered out loud what it would take for ME/CFS to be taken seriously by our funding agencies, and Ron said, “Well, it would take a pandemic.”
I was horrified, but I knew he was right. Infectious diseases can trigger chronic diseases like ME/CFS. Given the number of people who would become ill during a pandemic, it seemed inevitable that a true pandemic would dramatically increase the number of people living with ME/CFS.
Carr: Is there a history of increased diagnosis of chronic disease following pandemics?
Seltzer: We've seen pockets of ME/CFS and other, often post-viral diseases develop following other outbreaks. We might say these diseases are often triggered by viral infection rather than “caused,” per se because susceptibility can be hereditary.
I estimated on Twitter in April 2020 that COVID could double the number of people with ME/CFS. Unfortunately, it appears I was off by half or more. Studies show that 25% to more than 30% of COVID-19 patients experience long-term symptoms, many or most of which also occur with ME/CFS. The New York Times is currently reporting 46 million reported cases of COVID-19 in the U.S. alone.
Some people with persistent symptoms will gradually get better, but many will be chronically ill for the rest of their lives. Yet, I see little acknowledgment that COVID will lead to permanent disability. As a society, we don’t do well with the idea of “sick forever.” You're supposed to die or recover; that's what our culture can accept.
Carr: So, are you saying that COVID-19 can lead to ME/CFS? How do Long COVID and ME/CFS relate, and what are the implications for diagnosis?
Seltzer: I would say that Long COVID is a complex mix of symptoms that can indicate various diseases and syndromes. Some Long COVID patients have an ME/CFS-like set of symptoms that look like ME/CFS to an experienced clinician—whether they would meet the diagnostic criteria or not is another question. Based on the Patient-Led Research Collaborative research, I estimate that about 75% of Long COVID patients show signs of ME/CFS. The other 25% may have specific damage to an organ or organ system from the virus itself or another disease triggered by infection. Some people have co-morbidities strongly associated with ME/CFS, like postural tachycardia syndrome, or POTS, a kind of dysautonomia, but those may also occur on their own.
We’ve learned from ME/CFS that people with post-infectious syndromes may have a better chance of recovery and improvement early in the disease. People who promptly begin a treatment called pacing—being active when able and resting when tired—may have a better chance of getting better.
There is great value in advocacy groups of people with chronic diseases working together, but for clinical purposes, figuring out what's up with each patient on an individual level matters. I can't emphasize that enough. For example, it’s crucial that patients with post-exertional malaise (PEM), the cardinal symptom of ME/CFS and common with Long COVID, be identified and treated accordingly. If not, they may be prescribed “graded exercise,” a gradual intensification of physical exercise that worsens them. Graded exercise therapy has been removed from recommendations from the Centers for Disease Prevention and Control and, in the United Kingdom, the National Institute for Health and Care Excellence, or NICE, in recent years, as we have grown to understand that exertional intolerance is a distinct characteristic of the disease.
Because the ME/CFS community understands PEM and the potential for COVID to cause it, #MEAction developed a campaign early in the pandemic called #StopRestPace and worked hard to raise awareness about appropriate treatment. Pacing activity is the best strategy for preventing post-exertional malaise.
Carr: How important is post-exertional malaise to the diagnosis of ME/CFS? Is it difficult to recognize?
Seltzer: Once clinicians learn how to recognize the way patients describe symptoms of PEM, I don’t think they will miss a patient with ME/CFS again. Healthy people, including some clinicians, may attempt to connect pathological symptoms to something they have experienced as healthy individuals. Post-exertional malaise is different from feeling more tired than usual after exercising. In the context of ME/CFS and now Long COVID, malaise is a symptom that means feeling ill. Patients may even describe shock-like symptoms—lowered heart rate or blood pressure, decreased core body temperature—after exertion. PEM is not just feeling more tired or achy than normal after exertion, and it’s important to understand the difference.
I hope Long COVID will result in more people gaining an interest in really understanding these often-post-viral diseases. There’s no need to reinvent the wheel for Long COVID; with the research that’s been done on ME/CFS, we have a great starting point for diagnosis and treatment.
Carr: ME/CFS is often described as a condition that primarily affects women, especially white women of privilege. Do you think that’s an accurate representation?
Seltzer: One of my quests is to spread the word about ME/CFS to clinicians who serve Black communities. Community-based studies show that Black, Indigenous, and people of color (BIPOC) are slightly more likely to have ME/CFS than whites, but the diagnosis is practically barred for them because of bias and limited access. COVID has disproportionately affected BIPOC populations, so we should expect to see Long COVID and ME/CFS among those patients, too. Privileged white women are the ones who end up with a diagnosis because they have the time, money, and support to reach a diagnosis that is prohibitively inaccessible to many others. If they have a patient with fibromyalgia who also experiences PEM, they should consider adding ME/CFS to the differential diagnosis.
We have a long-standing problem in health care with disparities. In addition to working on racial justice and health equity, the key is to recognize that disabled folks are not some group of “others.” They are our friends, family, co-workers, and the people with whom we go to school and church. They're not strangers. They are us and we should take care of our own.
Additional reading and other information
The Voice of the Patient: Chronic Fatigue Syndrome and Myalgic Encephalomyelitis, 2013. One in a series of reports from the U.S. Food and Drug Administration’s Patient-Focused Drug Development Initiative.
Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: A Clinical Case Definition and Guidelines for Medical Practitioners, 2005, also known as the Canadian Consensus Document.
Chronic fatigue syndrome may hold keys to understanding post-Covid syndrome. STAT, July 21, 2020.
Long COVID Gains Acceptance as Many Questions Remain Unanswered, ImproveDx, January 2021.
Moving Toward Answers in ME/CFS, National Institute of Health’s Director’s blog, March 21, 2017.
The Chronic Illness Survey Adventure is a survey-based study of patient-reported symptoms of illnesses including ME/CFS, Long COVID, postural tachycardia syndrome. Sponsored by #MEAction, overseen by Jaime Seltzer, Director of Scientific and Medical Outreach.
Diagnostic criteria for ME/CFS proposed by the Institute of Medicine in 2015 include the following three symptoms:
1. Significant reduction in the ability to engage in work, school, or social and personal activities at pre-illness levels for more than 6 months. This is accompanied by newly experienced fatigue, not related to excessive exertion, and does not improve with rest.
2. Severe post-exertional malaise
3. Sleep that is not refreshing
Plus one of the following:
1. Cognitive impairment
2. Orthostatic intolerance—symptoms such as light-headedness or dizziness experienced on standing upright