Navigating Long COVID and ME/CFS Overlap
Alba Azola, MD discusses the challenges of diagnosing and managing Long COVID and its overlap with ME/CFS, emphasizing the need for individualized care and ongoing research.
In a recent interview with Alba Azola, MD lead author of the AAPM&R autonomic dysfunction guidance statement and a member of the Johns Hopkins Post-Acute COVID-19 Team, important insights were shared about the overlap between Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), two conditions that coincide with one another.
One of the key points discussed was how Long COVID can overlap with other conditions, such as ME/CFS. Long COVID, like ME/CFS, presents with a range of debilitating symptoms, including severe fatigue, post-exertional malaise (PEM), brain fog, and orthostatic intolerance. While these symptoms can mirror each other, the pathophysiology of Long COVID and ME/CFS remains an area of active investigation.
Azola explained that while both conditions share common symptoms, they are not necessarily the same. "I don't think that we are at a point where we can equate both things," she said. "I think that there are several, or there's a large group of Long COVID patients that do meet criteria for ME/CFS, and treating with symptom management that has been used in the past for pre-pandemic ME/CFS patients can be very effective for these patients as well."
She also noted that the definition of ME/CFS, according to the 2015 guidelines, includes the requirement of severe fatigue and loss of function lasting more than six months. Other diagnostic criteria include post-exertional malaise, brain fog, orthostatic intolerance, and unrefreshing sleep. These same symptoms are also commonly reported by individuals with Long COVID.
"The most recent definition was from June of 2024, by the National Academies of Medicine, and it defined it as symptoms that start after SARS-CoV-2 infection and last three months. And there is no particular kind of timing of the onset. It's not affected by the severity. So people with mild or asymptomatic illness can also develop Long COVID," Azola explained. "But Long COVID can also have other co-diagnoses. So it's not exclusive, right? So we have somebody who presents with new symptoms after Long COVID, and they may meet diagnostic criteria for ME, CFS."
According to the specific definition from the report defines Long COVID is a chronic condition that occurs after a COVID-19 infection and lasts for at least three months. It can present as continuous, relapsing, or progressive and affect multiple organ systems.
Key aspects of the definition:
- Long COVID can follow any severity of SARS-CoV-2 infection, including asymptomatic cases. Symptoms may appear weeks or months after the initial infection.
- It includes a wide range of symptoms, such as fatigue, difficulty concentrating, shortness of breath, and post-exertional malaise, as well as conditions like POTS, ME/CFS, and autoimmune diseases.
- Long COVID can significantly impair daily activities, impacting work, school, and self-care. Its effects can range from mild to severe and may persist for months or years.
- Diagnosis is based on clinical assessment, as no biomarker currently exists for confirmation.
- The report highlights the need for continued research, particularly on biomarkers, risk factors, and equity, as socioeconomic factors and stigma can affect diagnosis and treatment.
The report recommends broad adoption of this new definition to improve diagnosis, care, and research.
Azola further elaborated on how Long COVID can present with co-existing conditions, such as Postural Orthostatic Tachycardia Syndrome (POTS) or seronegative rheumatoid arthritis, highlighting the complexity of diagnosing and managing these patients. "You can also have Long COVID and POTS, or you can have Long COVID and seronegative rheumatoid arthritis. So there's... you can have combinations," she said.
One of the hallmark symptoms of both Long COVID and ME/CFS is post-exertional malaise (PEM), which Azola described as an out-of-proportion exacerbation of symptoms following even minimal activity. "Post-exertional malaise is not just feeling tired or, you know, feeling like you can walk up the steps," she explained. "Post-exertional malaise is an out-of-proportion onset of symptoms that range from neurological to musculoskeletal that come about with activity that was previously tolerated."
Azola emphasized that PEM is not the typical fatigue associated with exercise or strenuous activity but rather a profound worsening of symptoms that can occur after even minor exertion. Patients may experience body aches, tremors, headaches, worsening brain fog, sore throat, and other symptoms after engaging in light activities like walking to the pharmacy or going shopping. "These patients have severe impairments that don't allow them to be able to function as they did," she said.
As a physiatrist who has treated patients recovering from strokes, traumatic brain injury, and spinal cord injuries, Azola noted the parallels between these conditions and the challenges faced by Long COVID patients. "As a physiatrist that used to take care of these patients before, I see my Long COVID patients just the same," she said. "These patients have severe impairments that don't allow them to be able to function as they did."
In terms of treatment, Azola pointed out that rehabilitation protocols for ME/CFS patients pre-pandemic, particularly those focused on symptom management, can be effective for Long COVID patients as well. However, she acknowledged that further research is needed to fully understand the pathophysiology of Long COVID and how it may differ from or overlap with ME/CFS.
Research remains an essential part of understanding Long COVID and ME/CFS, particularly in understanding their underlying mechanisms and how best to treat them. "We don't know if the pathophysiology is the same, and that's going to be told. You know, with research we're working on using pre-pandemic ME, CFS as a kind of compare or control group to look and compare with those with post-pandemic SARS-CoV-2 onset ME/CFS," Azola explained.
Listen to previous interviews with Azola: Navigating Uncertainty And Raising Awareness About Long COVID
Sex-Specific Immune and Hormonal Factors Reveal How Long COVID Impacts Genders Differently
