Researchers recently have looked into historical outbreaks of myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), and their association with enteroviruses and other pathogens. In a paper, "The viral origin of myalgic encephalomyelitis/chronic fatigue syndrome," published in PLOS Pathogens, they explored several hypotheses related to the causes of ME/CFS, including a likely culprit in viral infections, particularly those from the enterovirus family.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, long-term illness that affects many body systems. People with ME/CFS are often not able to do their usual activities. At times, ME/CFS may confine them to bed. People with ME/CFS have severe fatigue and sleep problems. ME/CFS may get worse after people with the illness try to do as much as they want or need to do. This symptom is called post-exertional malaise (PEM). Other symptoms can include problems with thinking and concentrating, pain, and dizziness. (1)

The exact causes of ME/CFS are not fully understood, and it is considered a complex and multifactorial condition. Several theories and factors have been proposed as potential contributors to ME/CFS, but no single cause has been definitively identified.

Now researchers  make the case that some causes are more likely than others, including:

• Infections with the enterovirus family of viruses. This hypothesis is based on historical outbreaks of ME/CFS coinciding with outbreaks of diseases caused by enteroviruses, as well as evidence of chronic viral infection in some ME/CFS patients. While this could be causal to many more cases, identifying the specific virus that was infecting an individual who later acquired ME/CFS is not possible.
• Human herpesviruses (HHVs), such as Epstein-Barr virus and HHV-6. In ME/CFS, these are a potential source. Some ME/CFS patients report an acute infection with HHVs at the onset of their illness, and reactivation of these viruses may contribute to the condition.
• Post-viral syndromes, including post-acute sequelae of COVID-19 (PASC). These are included in an emerging area of clinical understanding. Some individuals with mild or asymptomatic COVID-19 later experience a post-viral illness that shares symptoms with ME/CFS. This raises questions about the relationship between other lesser-known or less apparent infections and their potential to cause post-viral syndromes and ME/CFS.

In the light of a major viral pandemic with lingering ME/CFS conditions, the researchers compiled information on historical ME/CFS outbreaks with studies on infections like Epstein-Barr virus, Q fever, Ross River virus, influenza and previous ME/CFS patient research, and interrogated varying criteria used by research groups and clinicians to define ME/CFS.

Focusing on viral infections is an intriguing investigative path, as there are already many conditions associated with ME/CFS, almost as if a researcher could pick anywhere to start pulling at the connecting threads of the condition.

There are immune system abnormalities linked to ME/CFS; genetic factors may play a role in susceptibility. The central nervous system has associations with many of the symptoms. A host of potential environmental factors, such as toxins, stress, and trauma may be implicated.

Recent research indicates issues with cellular energy metabolism, particularly involving mitochondria, leading to the fatigue and reduced stamina. Hormonal dysregulation and/or gut microbiota could play a role, and the list goes on.

The researchers argue that there is no proof that multiple pathogens can cause ME/CFS. They suggest that the hypothesis persists due to the overinterpretation of data from previous studies where the initial infection type was either missed, inferred but not verified, or where the symptom survey did not include ME/CFS defining criteria.

Currently, there is no specific diagnostic test or universally effective treatment for ME/CFS, which makes it a challenging condition to manage. Treatment typically focuses on symptom management by attempting to improve the quality of life for individuals through traditional, good doctorly advice of "Exercise regularly, eat right, get plenty of sleep." The condition can be frustrating for patients who follow such advice and yet find no relief.

Before the SARS-CoV-2 pandemic, the ability of RNA viruses to persist in tissues for long periods was largely ignored. Recognizing that EVs are prime candidates for causing ME/CFS suggests the importance of pursuing a relevant inquiry into this diverse virus family.

Sixty-five million long COVID sufferers worldwide have prompted the US government to devise PASC to describe a post-acute illness syndrome. Most relevant to ME/CFS is that some people who suffered mild or asymptomatic cases of COVID-19 later began experiencing a post-viral illness that fulfills most or even all of the criteria for ME/CFS.

Increasingly, these people are told by their doctors that they have ME/CFS, but the diagnostic criteria were created six years before SARS-CoV-2 emerged. Those who acquired ME/CFS before the SARS-CoV-2 outbreak also number in the tens of millions, and the source of their initial infection often remains a mystery.

Scientists suggest that the overlap in symptoms between some forms of post-COVID illness and ME/CFS suggests that disruptions in the same pathways may be occurring in both diseases, but to conclude that the two syndromes are identical without more data, especially at the molecular level, is currently unwarranted. Any SARS-specific antiviral treatments will not be effective for ME/CFS patients.

If it were not for COVID-19 hitting everywhere all at once, ME/CFS caused by SARS-CoV-2 might also be flying under the radar of the clinical and research communities. Now that the link between a viral infection and ME/CFS has been firmly detected, these scientists are urging an inquiry into the prime candidate for previously existing ME/CFS cases.

Source: Maureen R. Hanson et al, The viral origin of myalgic encephalomyelitis/chronic fatigue syndrome, PLOS Pathogens (2023). DOI: 10.1371/journal.ppat.1011523

Footnotes: 

1. https://www.cdc.gov/me-cfs/index.html#:~:text=Myalgic%20encephalomy...(ME%2FCFS)%20is,severe%20fatigue%20and%20sleep%20problems.

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Blood test for chronic fatigue syndrome found to be 91% accurate

An international team of medical researchers has announced the development of a blood test for chronic fatigue syndrome. The test is reportedly 91% accurate. In their paper published in the journal Advanced Science, the group describes their test, how it works and how well it has fared during initial testing.

Myalgic encephalomyelitis also known as chronic fatigue syndrome, (ME/CFS), is a medical condition in which a person feels abnormally fatigued. Because it is difficult to diagnose, some in the medical community are skeptical that it is a real illness. Over the past decade, more of the medical community has acknowledged it as a real condition and has recognized that it can be debilitating. Still, diagnosis is difficult and can be a lengthy process. In this new effort, the research team developed what appears to be simple test for the condition.

Thinking that the root cause of ME/CFS is likely a problem with energy function in cells, the researchers looked for a way to test such a function using existing tools. They narrowed their testing to peripheral blood mononuclear cells, which are cells that have a round nucleus—such as T cells, monocytes and lymphocytes.

Prior research has suggested that these cells may play a role in ME/CFS. But because there is no test of such cells that can be used to measure energy function, the team turned to a tool not normally used in medical testing labs—Raman spectroscopy, which is normally used by chemists to identify molecular fingerprints. It works by comparing vibrational modes of molecules.

Thinking that there might be a difference in vibrations of single cells between people who have ME/CFS and those who do not, the team tested blood samples from 61 patients with the disorder and 16 without. They found a clear difference. Inspired by their results, they built an AI app for processing the results in large numbers of people and then tested their system on 2,000 cells from 98 patients. They found the system to be 91% accurate. The team plans to continue their work by testing larger samples but feel confident that they have at last found a test for ME/CFS.

Jiabao Xu et al, Developing a Blood Cell‐Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells, Advanced Science (2023). DOI: 10.1002/advs.202302146