Driving research of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS),
Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia and Long Covid

Stress-Activated MicroRNAs
in ME / CFS Pathogenesis


We designed a clinical intervention, safely producing a post-exertional malaise (PEM), a hallmark symptom of ME / CFS. We hypothesized that a standardized stress-test inducing PEM, will reveal a more specific disease signature associated with ME / CFS symptoms. In that context, we investigated the role of circulating microRNAs, which are small non-coding RNA molecules that can be detected in the blood as well as in other biological fluids.


Studying microRNAs might help to bridge the conceptual gap between genetic predisposition and environmental factors causing ME / CFS or exacerbating specific symptoms. Equally important, the design of a portable clinical intervention allows investigating severely ill persons with ME / CFS, especially the ones that are housebound.


  • This strategy led us to identify 32 circulating microRNAs in a case-control cohort.
  • Several of the miRNAs identified in our discovery cohort are associated with inflammation, regulation of immunity and/or a physiological response to exercise (endurance regulators).
  • Implementation of bioinformatics tools like Machine Learning algorithm (Random Forest Algorithm) led to a validation of a first diagnostic panel of 8 microRNAs (miR-28-5p, miR-29a-5p, miR-127-3p, miR-140-5p, miR-374b-5p, miR-486-5p, miR-3620-3p and miR-6819-3p) using a dataset of individuals with ME / CFS and matched healthy controls.
  • This panel has a predictive accuracy of 90% with a sensitivity of 100% and a specificity of 75% when the expression of each microRNA is compared after the stess-test versus their respective values at baseline (without stimulation). Conversely, when only the baseline values are used (without the stress-test), the predictive accuracy is lowered to 60% with a sensitivity of 71% and a specificity of 33% (non-specific). These preliminary results clearly indicated the superiority of our stress-test approach to reveal the molecular signature underlying ME / CFS.
  • This approach led also to an unbiased method to separate the persons with ME / CFS, called clustering, along three distinct clusters showing specific correlations between each cluster and symptom severity. Indeed, persons with ME / CFS classified in cluster 1 exhibit less general fatigue than those classified into cluster 2 and 3, while individuals in cluster 3 suffer of more severe sleep disturbances and PEM.
  • Interestingly, high expression of specific circulating microRNAs could help in predicting the respond toward specific treatment like Ampligen, Rituximab and many others.
Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation®

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Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME / CFS) Post Treatment Lyme Disease Syndrome (PTLDS), Fibromyalgia Leading Research. Delivering Hope.Open Medicine Foundation®

Averting a second pandemic:

Open Medicine Foundation leads groundbreaking international study of

Long COVID’s conversion to ME/CFS

AGOURA HILLS, CALIF.  — Open Medicine Foundation (OMF) is leading a large-scale international collaborative study investigating the potential conversion of Post-Acute Sequelae SARS-CoV-2 infection — more commonly known as Long COVID or Post-COVID Syndrome —  to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a chronic, life-altering disease with no known cause, diagnostic test or FDA approved treatments available.

Up to 2.5 million people in the U.S. alone suffer from ME/CFS; the COVID-19 pandemic could at least double that number. An estimated 35 percent of Americans who had COVID-19 have failed to fully recover several months after infection, prompting many to call it “a potential second pandemic.”

OMF recognized a familiar health crisis emerging, one with eerie similarities to ME/CFS. This crisis presented a unique opportunity to understand how a viral infection — in this case COVID-19 — may develop into ME/CFS in some patients. The goal is to find targeted treatments for ME/CFS patients and ultimately prevent its onset in people infected with SARS-CoV-2 or other infections.

The federal government is only now investing in Post-COVID research, with no focus on its connection to ME/CFS. OMF has already engaged researchers for the largest-scale study of its kind, solely supported by private donors who have contributed over one million dollars to date. When fully funded, the five million dollar, three-year study will be conducted across the globe at OMF funded Collaborative Research Centers, led by some of the world’s top researchers and ME/CFS experts.


In a significant percentage of patients, infections preceded their development of ME/CFS.  For example, according to the CDC about one in ten infected with Epstein-Barr virus, Ross River virus, or Coxiella burnetti develop symptoms that meet the criteria for ME/CFS.


The ability to follow the development of ME/CFS from a known viral infection is unprecedented to date and crucial to researchers’ understanding of the disease. The focus of this study is to find the biological differences between persons returning to good health after COVID-19 and persons who remained ill more than six months after infection and developed ME/CFS.  Understanding these alterations in key pathways can lead to groundbreaking discoveries including new biomarkers, drug targets, and prevention and treatment strategies.


About Open Medicine Foundation

Established in 2012, Open Medicine Foundation leads the largest, concerted worldwide nonprofit effort to diagnose, treat, and prevent ME/CFS and related chronic, complex diseases such as Post Treatment Lyme Disease Syndrome, Fibromyalgia, and Post COVID. OMF adds urgency to the search for answers by driving transformational philanthropy into global research. We have raised over $28 Million from private donors and facilitated and funded the establishment of six prestigious ME/CFS Collaborative Research Centers around the world. To learn more, visit www.omf.ngo.


Heather Ah San

Development and Communications Manager