Community Advisory Committee Develops Priorities for ME/CFS Research

The Community Advisory Committee (CAC) for the NIH ME/CFS Research Network was established to bridge the gap between researchers and the ME/CFS community with the goal of accelerating the pace of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) research. The CAC is a group of 15 individuals from various professional backgrounds, all of whom have lived experience of the disease.

The CAC Research Priorities working group has authored a report on the challenges and priorities to be addressed to achieve needed outcomes for people with ME/CFS. This has become especially urgent given the large number of people who already have, and are expected to develop, ME/CFS following COVID-19.

ME/CFS is a debilitating, chronic, complex disease that most often follows an infection and is associated with neurological, autonomic, immunological, and metabolic abnormalities. Patients experience a substantial impairment in functioning, and symptoms such as sleep dysfunction, cognitive impairment, orthostatic intolerance, pain, fatigue, and the hallmark post-exertional malaise (PEM), an exacerbation of symptoms following even small amounts of previously tolerated activity. An estimated 836,000 to 2.5 million Americans suffer from ME/CFS with a greater prevalence in females, adults and possibly people who are Black and Latinx. There are no validated biomarkers or FDA-approved treatments and patients can struggle to access adequate clinical care. An estimated 25% are homebound or bedbound and 75% are unable to work. Recovery is rare and patients can remain ill for decades.

Progress in understanding the etiology of ME/CFS and developing biomarkers and treatments has been constrained by a number of interrelated challenges, such as the inherent complexity and heterogeneity of the disease, inadequate study methods, challenges in collaborating across all stakeholders, misunderstanding about the nature of the disease, and lack of research funding and researchers in the field. But even with these challenges, substantial progress has been made in understanding some of the underlying pathology.

The pandemic has created the tragic opportunity to finally understand how an infection can result in chronic illness. At the same time, the knowledge and expertise gained from years of ME/CFS research has provided valuable insights for Long COVID research.

Leveraging this opportunity for ME/CFS requires ME/CFS-specific funding and a ME/CFS strategic research plan to expedite progress in ME/CFS diagnostics and treatments. It also requires the integration of learnings from ME/CFS research into the PASC strategy, not only to help accelerate research in Long COVID but to better understand ME/CFS onset, natural history, and pathology. A natural experiment is underway which cannot be replicated, and this calls for swift, decisive action before the window of opportunity to study early-onset ME/CFS closes as the pandemic resolves.

People with ME/CFS, including those who have developed ME/CFS following COVID-19, are waiting.

The CAC Research Priorities working group developed this comprehensive but concise report outlining the long-standing barriers that have constrained progress in ME/CFS and strategies for their resolution, as well as key short and longer term research priorities that need to be progressed to accelerate meaningful research and achieve outcomes for people with ME/CFS, including those whose ME/CFS developed following COVID-19. These recommendations can be used by researchers to generate new study designs and refine existing goals, facilitate collaborations between research domains and stakeholders, and by federal and private funders to guide award distribution and agenda setting. 

Click here to download the CAC Research Priorities Report

The Research Priorities working group is available and eager to discuss the contents of this document with researchers. Please contact us at any time at: CAC.MECFS@gmail.com

The authors of this guide are: Mary Dimmock, Rochelle Joslyn (chair), Sabrina Poirier, Jaime Seltzer and CAC Director, Allison Kanas.

This work was supported by US Public Health Service grant 5U54AI138370 and 5U24NS105535. This content does not represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health.

Community Advisory Committee – Guidelines for the Design of Clinical Studies in ME/CFS

The Community Advisory Committee (CAC) for the NIH ME/CFS Research Network was established to bridge the gap between researchers and the ME/CFS community with the goal of accelerating the pace of ME/CFS research. The CAC is a group of 15 individuals from various professional backgrounds, all of whom have lived experience of the disease.

The CAC – Study Feasibility working group developed this quick reference guide to aid researchers in the design of clinical studies and the development of IRB protocols for studies involving the ME/CFS population. These recommendations provide the patient perspective on accommodating the unique sensitivities and limitations of the population to produce more robust studies by improving study retention and completion.  

The Study Feasibility working group will be holding informational sessions to discuss items related to the submission of the NIH CRC grant applications on the following Wednesdays at 3PM ET: May 4, May 11 and May 18, 2022: https://columbiacuimc.zoom.us/j/98393290268

Researchers, study coordinators and/or administrators are encouraged to contact us at any time at: CAC.MECFS@gmail.com

The authors of this guide and the hosts of the upcoming informational sessions are: Kathi Kuehnel, Cherylle McFarlane, Jaime Seltzer (chair) and Susan Taylor-Brown (co-chair) and CAC Director, Allison Kanas.

Eligibility Criteria

ME/CFS case selection criteria have historically been inconsistent. To ensure compatibility of study data and results, the use of following case selection criteria is highly recommended. More than one set of criteria may be used to determine subject eligibility. These definitions include the cardinal symptom of post-exertional malaise (PEM).

Instrumentation & Measurement Tools

  • Use NINDS Common Data Elements
  • Consider incorporating the use of wearable devices to measure activity levels
  • Consider incorporating the use of symptom tracking apps, such as You+M.E.

Recruitment

Recruiting ME/CFS participants can be difficult due to barriers to diagnosis. The disease causes fatigue and may feature sensory sensitivities, cognitive impairment, and a limited ability to work, contributing to physical and economic barriers to participation.

General Strategies

Target Populations

Many research studies have included primarily white women with access to ME/CFS medical specialists, increasing the risk for sampling bias. Black, Indigenous and People of Color (BIPOC) patients, the severely ill, children, adolescents, and men often go undiagnosed, and thus are often under-represented in studies. Sedentary controls are recommended to rule out deconditioning as a potential confound.

Severely ill subjects

Since 25% of people with ME/CFS are housebound or bedbound, their enrollment in research studies poses a significant challenge. Without inclusion of the severely ill, the study findings may not be generalizable. Potential approaches for the recruitment of severely ill subjects include:

  • Partnering with multiple ME clinics and/or clinicians to reach recruitment goals for severe patients
  • Contacting social media groups for severely ill patients and caregivers

BIPOC populations

Recruiting participants who are Black, Indigenous and People of Color (BIPOC) may pose a challenge due to documented health care disparities in these populations. Under-representation in studies is not just a health equity concern but affects the quality and generalizability of findings. The use of the DePaul Symptom Questionnaire (DSQ) may allow for an increased diagnosis rate, thus expanding the potential subject pool. Oversampling in underserved and/or underrepresented populations is recommended. Suggestions for recruiting BIPOC subjects include:

  • Contact:
    • Federally Qualified Health Centers and other medical providers or public health care clincs that serve BIPOC communities
    • Local ESLlearning centers and translate recruitment flyers into multiple languages
    • Organizations such as WEGO Health to identify patient leaders
    • Religious, spiritual and community centers
    • Veterans Administration Clinics
  • Advertise in outlets focused on the target population, including:
    • Articles in magazines/journals
    • Podcasts
    • Social media
Men
Sedentary controls

Matching healthy controls based on activity level, along with demographic data is recommended. Suggested sources for reaching sedentary controls include:

  • College campuses for young, sedentary controls from university health centers
  • Physical therapy practices with access to subjects who are healthy yet sedentary
  • Clinical entities, such as the Bateman-Horne Center, with a connection to a university hospital system, or large-scale care providers such as Kaiser or One Medical

Accommodations & Study Retention

Providing appropriate accommodations helps to ensure subject retention and study completion.

General Strategies

  • Ensure that all study materials are available in advance, online, and are printable
  • Use disability-accessible fonts and formatting for all study materials. Using boldface on key concepts may be helpful
  • Whenever feasible, hold study visits remotely 
  • Provide flexible appointment options for in-person visits
  • Avoid early morning start time and limit the duration of visits
  • For the severely ill, consider home visits with a mobile phlebotomist or research nurse
  • Consider enlisting a patient advocate, sensitive to the needs of the population, to help subjects complete the study materials and navigate the visits
  • Provide transportation assistance by arranging transportation services (car, taxi, medical van, ambulance) or provide travel vouchers (taxi, subway cards, bus tickets, medical vans) or provide transportation reimbursement
  • Provide compensation for study participation preferably in the form of cash or a credit card. Single vendor gift cards are discouraged
  • Provide a listing of social worker support services
  • Create a study resources package and/or accompanying video to include:
    • Directions and maps to the room location, including transit, road, campus and building maps
    • List of available transportation options
    • A study summary explaining the study goals and an explanation of the activities to be performed at each study visit
    • Link to online/printable study materials
    • Directions for downloading and using a screen reader for devices
    • List of available childcare options with contact information
    • Contact information for study coordinator and on-site clinic office 

Study Visit Recommendations

Before the visit

Contact the participant or caregiver via phone or email to:

  • Ensure they and/or their caregivers received the study resources package
  • Answer any questions
  • Remind them of the transportation options and offer additional assistance
  • Ensure they have all necessary maps, including a campus and building map
  • Inquire if an escort or a wheelchair is needed
  • Offer priority parking, if available
During the visit

Offer participants:

  • A quiet, dark area where they can rest in a reclined position
  • Accommodations for accompanying caregivers
  • A screen reader for viewing electronic study materials
  • Printed copies of study materials, in case they have difficulty reading a screen

Blood Sample Collection

  • Advise participants to maximize fluid intake before, during and after blood draws.
  • Provide water, free-of-common-allergen snacks, and/or electrolyte powder
  • Provide a skilled phlebotomist. People with ME/CFS are often “hard sticks”
  • Remember that POTS is often comorbid with ME/CFS and increases the risk of syncope
  • People with ME/CFS may have low blood volume, so it is especially important to set a fixed upper limit for the total volume drawn. While no more than 120mL are recommended for ill adults in a 24 hour period, we recommend <80mL for people with ME/CFS.
  • Coordinate draws for subjects participating in more than one study to avoid exceeding recommended blood draw volume limit

After the visit

Contact the subject or caregiver via phone or email to: 

  • Thank them for their participation 
  • Ask how they tolerated the experience and monitor for PEM symptoms
  • Ensure they received compensation for their participation 
  • Remind them of upcoming study visits or activities 
  • Ensure they have the coordinators’ contact information 
  • Remind them they may be contacted regarding future research, if applicable

Special Considerations

It is important to remain aware that people with ME/CFS are often more ill than they may appear. Many have been ill for decades. They may have sensory sensitivities, moderate cognitive dysfunction and may experience PEM following either physical or mental exertion. Many report symptom fluctuations based on seasonality. They also may be less trusting of the medical community because they have often been incorrectly diagnosed, marginalized, and stigmatized. For these reasons:

  • Use clear and accessible language about how study data will be used and stored
  • Consider the potential for seasonality differences in the study design
  • Consider incorporating long-term follow-up in the study design to ensure that subjects’ symptoms have not worsened following study participation
  • Clearly define the differences between researchers and clinicians
  • Explain whether the subject will have access to study data or results or obtain medical care as a part of their participation
  • Design studies that do not require the subjects to cease medical interventions as this may induce negative long-term health consequences

Download Guidelines for the Design of Clinical Studies in ME/CFS Here

For an in-depth, expanded presentation by Jaime Seltzer, Director of Scientific and Medical Outreach at #MEAction and Chair of the Community Advisory Committee – Study Feasibility Working Group, entitled, “ME/CFS Study Design and Recruitment: A Toolkit for Study Coordinators” given at the NIH ME/CFS Research Network annual meeting on October 7, 2021” please watch here:

This work was supported by US Public Health Service grant 5U54AI138370 and 5U24NS105535. The content does not represent the official views of the National Institute of Neurological Disorders and Stroke or the National Institutes of Health.

Community Advisory Committee Introduces Guidelines to Accelerate Meaningful ME/CFS Research

by Therese Russo and Kathi Kuehnel, lead authors on behalf of the Community Advisory Committee

Researchers from across the NIH’s ME/CFS Collaborative Research Center (CRC) consortium held a two-day network meeting in October to share findings from their past four years of NIH-funded research.  This year, the Community Advisory Committee (CAC) was invited to participate and also present its work. With support from the NIH, Columbia launched the CAC with the goals of increasing stakeholder communication and research participation, and accelerating the pace of ME/CFS research.

Centering the community perspective by including the CAC in the consortium’s meetings represents a shift from the norm: to the ME/CFS community, research has often seemed like a mysterious “black box,” with few mechanisms to ensure transparency and engagement.  Patients often wait years for even interim updates on studies. People with ME/CFS have advocated for greater involvement at all stages of the research process for years, and patient advocacy was crucial to the establishment of the CAC.

Partnering with people who have lived experience with a disease leads to research that has a deeper impact and better outcomes in patient care 1. Meaningful patient inclusion also improves grant writing, recruitment strategy, dissemination strategy, patient interviews, data collection and both tool development and refinement. Despite these benefits, there are few efforts to include patient perspectives in ME/CFS research. The CAC was created to more effectively engage patients throughout the research cycle. 

“Most of us live with this awful illness every single day. We never get to turn it off, leave it at the office or forget about it. We never escape its harsh reality. Every day, we know that many people are waking up and asking themselves, can I live like this any longer?… We have everything riding on your research. Every hope. Every dream. We are fully invested in your success….partner with us and together let’s create impact with and for a community that desperately needs us to get this right.”

-Sabrina Poirier, CAC Member at 2020 NIH CRC Annual Meeting 

The CAC is composed of 15 people with ME/CFS and/or family members of people with ME/CFS. Members come from diverse personal and professional backgrounds, including research, health care, advocacy, education, law, politics, health policy, social work, and community building.  Members also include representatives from ME/CFS nonprofits and research organizations, including #MEAction, the Solve ME/CFS Initiative (Solve M.E.), the Bateman Horne Center, Doctors with M.E., U.S. ME/CFS Clinician Coalition and ICanCME. 

Taken together, this committee’s decades of lived experience with the disease, and the members’ deep connections in the ME/CFS community, position the group to provide insight and guidance on what research will most benefit the patient community and how researchers can design studies that are feasible and practical from the perspective of people with ME/CFS. 

At the October network meeting, the Director of Scientific & Medical Outreach at #MEAction and CAC member Jaime Seltzer presented a draft of the CAC’s Study Feasibility Working Group’s2 paper ME/CFS Study Design and Recruitment: A Toolkit for Researchers and Research Coordinators. The Toolkit guides researchers in best practices for recruiting, selecting, and retaining research subjects; accommodating their related medical, sensory, and energy issues; and engaging people with lived disease experience in research design, implementation, and dissemination.

“There is abundant evidence that patient involvement improves research quality,” says Seltzer. “Studies in which patients shape or direct research have the most successful recruitment, and using in-group language can elicit more honest answers and ‘buy-in’ in epidemiological surveys. Patient-oriented research has also been shown to affect healthcare outcomes like diagnostic rates and earlier interventions.”

Dr. Rochelle Joslyn, PhD (Immunology), who has more than a decade of experience in human biomedical research, provided the CAC’s Research Priorities Working Group’s assessment on key barriers and urgent needs in ME/CFS research, as outlined in a comprehensive research priorities document that will be published soon. 

The presentation included a “Gordian Knot” image representing the interplay of biological, medical, social, legal and political constraints that have inhibited research and kept ME/CFS patients sick and without treatment for decades. The CAC urged members of the CRCs and NIH to bring about real change and deliver meaningful outcomes for people living with ME/CFS by working together to address these long-standing issues.

The Gordian Knot represents the interplay of biological, medical, social, legal and political constraints that have inhibited research and kept ME/CFS patients sick and without treatment for decades.
Illustration by Alice Ella.

“Patients’ lived experience, diverse and complementary skills, and deep connection to the broader ME community are critical assets that must be leveraged to successfully move the field,” says Dr. Joslyn.

There is important overlap in the recommendations from both presentations. Both underscored the need for:

  1. A standardized, high-quality ME/CFS case definition, and patient selection methods3; 
  2. Consistent, objective measurement of the hallmark symptom – post exertional malaise (PEM); and 
  3. Intentional, robust inclusion of Black, Indigenous, and People of Color (BIPOC) and severely ill people as research subjects. 

These presentations were starting points for an ongoing conversation between researchers and the CAC members. Collaboration and consensus-building amongst people with different positions and perspectives in research and medicine necessarily takes time and steady communication. But ultimately, it yields more robust, patient-centered outcomes. 

We will provide detailed reports on both the CAC’s Study Design Toolkit and Research Priorities in future blog posts. 

In months to come, we will begin posting the new ME/CFS Research Network Webinar series, which will feature presentations from across the network, along with panel discussions to delve deeper and answer the community’s questions. Research topics will include immune dysregulation, disordered energy metabolism, gastrointestinal dysbiosis, and other biological abnormalities in ME/CFS patients. 

The NIH CRCs have begun to develop biomarker and clinical trial hypotheses, which we hope to see funded in the upcoming NIH competitive renewal applications.  And not insignificantly, the field is beginning to see consistent findings across the Centers. This reproducibility is essential for building confidence in the validity and reliability of key results. 

The CAC’s goal is to continue making this information more accessible to the community of people living with ME/CFS and related conditions, for a more informed, empowered global community. Stay tuned. 

1For several papers on these topics see the following:

  • Forsythe LP, Carman KL, Szydlowski V, Fayish L, Davidson L, Hickam DH, Hall C, Bhat G, Neu D, Stewart L, Jalowsky M, Aronson N, Anyanwu CU. Patient Engagement In Research: Early Findings From The Patient-Centered Outcomes Research Institute. Health Aff (Millwood). 2019 Mar;38(3):359-367. doi: 10.1377/hlthaff.2018.05067. PMID: 30830822;
  • Esmail L, Moore E, Rein A. Evaluating patient and stakeholder engagement in research: moving from theory to practice. J Comp Eff Res. 2015 Mar;4(2):133-45. doi: 10.2217/cer.14.79. PMID: 25825842;
  • Ennis L, Wykes T. Impact of patient involvement in mental health research: longitudinal study. Br J Psychiatry. 2013 Nov;203(5):381-6. doi: 10.1192/bjp.bp.112.119818. Epub 2013 Sep 12. PMID: 24029538

2For more information about the working group structure of this Community Advisory Committee, see this October 2020 blog entry. 

3The 2011 NIH State of Knowledge report reads: “According to presenters, working toward a single, more usable and accurate case definition for this illness would create a more solid foundation for research and ultimately benefit people living with this illness.” For more details, see the full report.  

The Coding Problem—Why no American can develop ME/CFS, including after COVID

Mary Dimmock

Please sign this petition to fix the coding problem that makes Americans with ME/CFS invisible.

If a tree falls in the forest, does it make a sound? And if an American develops ME/CFS, would the US disease tracking systems know about it? Philosophers may debate the first question but the answer to the second is decidedly NO.

As far as US disease tracking systems are concerned, the 1-2.5 million Americans with ME/CFS patients are invisible. You can’t die of ME/CFS in the US. You won’t experience any morbidity (suffering, impairment) from ME/CFS. And you certainly won’t develop ME/CFS following an acute COVID-19 infection, in spite of the remarkable similarities noted by many researchers, including NIH’s Dr. Anthony Fauci.

That’s because the US ICD codes used to track diseases do not include a code for the term ME/CFS, the name adopted by US federal agencies and in clinical guidance. At the same time, the term “chronic fatigue syndrome,” the term most often used by US doctors, has been assigned the same ICD code as the symptom of “chronic fatigue, unspecified.”

As a result, virtually all cases of ME/CFS are effectively lost in a bucket of unspecified chronic fatigue due to any cause.

These ICD codes, short for the International Classification of Diseases, are maintained by the World Health Organization (WHO) as a globally agreed classification system to support tracking of diseases across countries. ICD codes are used to track disease mortality and morbidity and to assess disease burden and healthcare utilization and cost. In the US, they are used in insurance billing. They show up in electronic health records and are used to research issues such as the causes of and long term impact of diseases. NIH and CDC have both announced extensive plans to use electronic health records to do exactly that kind of research into Long COVID.  

But as CDC reported at a recent conference, ICD codes alone are not sufficient to find the cases of ME/CFS in these electronic health records. Doing that required an expensive and time consuming manual chart review. Such manual reviews are unlikely to be done in reporting on mortality and morbidity or in most research using electronic health records. This includes those planned Long COVID studies. The obvious impact on Americans with ME/CFS is huge.

How is this possible and why has it never been fixed?

In WHO’s current ICD, the ICD-10, ME and CFS are classified in the neurological chapter. The WHO also allows countries to create their own versions as long as they follow WHO standards. When the US implemented its version, the ICD-10-CM, in 2015, it reclassified CFS from the neurological chapter to the Symptoms and Signs chapter and gave it the same code as the symptom of “chronic fatigue, unspecified.” This is not aligned with the WHO classification and no other country has done this, making it a uniquely US problem.

Proposals to fix this were submitted in 2011, 2012, and 2018 to CDC’s National Center for Health Statistics (NCHS), the US group that manages the ICD-10-CM. But NCHS rejected each of those proposals because of lack of stakeholder consensus, including from patients and coding associations, on how to fix the problem. As a result, cases of ME/CFS are still coded as “chronic fatigue, unspecified.”

This year, seven ME/CFS organizations (**) submitted a fourth proposal, asking for the most basic change to move this forward – to add the term ME/CFS to the ICD-10-CM and support both viral and nonviral triggers for the disease. NCHS then added additional coding changes, including some that were previously rejected.

This situation is such a gordian knot that no single set of recommendations can possibly address all stakeholder concerns. But the status quo is completely unacceptable because it leaves those with ME/CFS invisible – not coded, not counted, not researched.

For the sake of the 1-2.5 million Americans who had ME/CFS before the pandemic and for the sake of those who could develop ME/CFS following COVID-19, we must find a way to resolve this problem. Continuing to lose track of people with ME/CS in US medical records, tracking systems, and research is simply not an option.

Please sign this petition calling on the US to fix its ME/CFS coding problem.

Background on the ICD and why this is important is available on the petition site.

(*) Thanks to Dr. Robert K. Naviaux, University of California, San Diego (UCSD), CA for the idea for the title.

(**) The organizations submitting this proposal were: The International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, #MEAction, Open Medicine Foundation, Solve M.E., Massachusetts ME/CFS & FM Association, the Minnesota ME/CFS Alliance, Pandora Org. 

Redox Imbalance: A Core Feature of ME/CFS and Acute COVID-19

Anthony L. Komaroff, MD

ME/CFS is defined exclusively by symptoms—subjective experiences that are hard to verify by objective testing. For that reason, since interest in ME/CFS began to grow in the 1980s, scientists have been looking for evidence of underlying objective abnormalities that might explain the symptoms.

A recent review, published August 24, 2021, in the Proceedings of the National Academy of Sciences USA, summarizes in detail the evidence demonstrating one of the several objective abnormalities in people with ME/CFS and acute COVID-19: redox imbalance.1 It speculates that redox imbalance may also be present in post-acute COVID-19 syndrome, or “long COVID-19”, although this remains to be studied.

Redox imbalance occurs when the molecules that are oxidants (particularly “free radicals” or reactive oxygen species) exceed the number of molecules that are antioxidants. Essentially, redox imbalance is the same as the more familiar term of “oxidative stress”.

Persistent redox imbalance can damage a body’s cells. Specifically, it can damage the membranes of a cell, and the proteins and DNA within a cell. Redox imbalance is present in many diseases: it is not unique to COVID-19 or ME/CFS.

The review summarizes how redox imbalance is connected to other abnormalities that also have been identified in people with ME/CFS, acute COVID-19 and possibly post-acute COVID-19 syndrome: abnormal function of mitochondria (the sources of cellular energy molecules, or ATP), and chronic inflammation. 

Indeed, the connections between these different abnormalities set up the possibility of several vicious cycles.  For example: 1) Chronic inflammation leads to redox imbalance, and then redox imbalance causes some cells to die prematurely, leading to chronic inflammation;  2) Abnormal function of mitochondria leads to redox imbalance, and the free radicals present in redox imbalance then damage the mitochondria, impairing their function even more; 3) Abnormal function of mitochondria leads to reduced ATP production, which can impair the ability of the immune system to keep viruses that are “asleep” in our body from “reawakening” and multiplying; the viruses then lead to further inflammation, redox imbalance and damage to mitochondria.

The authors of the review are Dr. Bindu Paul, a molecular neuroscientist and faculty member at the Johns Hopkins University School of Medicine; Marian Lemle (the parent of someone who suffered from ME/CFS, who is affiliated with the Solve ME/CFS Initiative); myself (a member of the Center for Solutions for ME/CFS team at Columbia University, and of the faculty of Harvard Medical School); and Dr. Solomon H. Snyder, also from Johns Hopkins. Dr. Snyder is one of the most distinguished and honored neuroscientists in history.

The review had its beginning when Marian Lemle approached me several years ago with the hypothesis that abnormalities in the production of hydrogen sulfide gas, might be one trigger of the symptoms of ME/CFS. Hydrogen sulfide is important in brain and immune function, affects ATP production, and influences redox balance. Ms. Lemle had recently published her hypothesis2, and I was impressed by it. I suggested that she contact Drs. Paul and Snyder, since I knew their laboratories were world-renowned leaders in this field.

The goal of the review is to stimulate the global research community to study the role of redox imbalance in ME/CFS and in post-acute COVID-19 syndrome—as well as the connections between redox imbalance, inflammation, mitochondrial function and impaired energy metabolism.

This theory has implications for treatment. Treatments that reduce redox imbalance, or that reduce the other abnormalities that can lead to redox imbalance, should be considered candidates to study in people with ME/CFS or post-acute COVID-19 syndrome. Since treatments with single antioxidants have not proved very effective in treating various illnesses characterized by redox imbalance, it may require a “cocktail” of several antioxidants and/or anti-inflammatory medications to be successful.

It’s too soon to know whether this hypothesis will prove fruitful. But if it does, it will be because a patient advocate and devoted mother took it upon herself to look for possible scientific explanations for ME/CFS, developed a very plausible hypothesis, wrote an article about the hypothesis that was accepted for publication, and brought the hypothesis to scientists in a position to pursue it. We need more such partnerships.

References

  1. Paul BD, Lemle MD, Komaroff AL, Snyder SH.  Redox imbalance links COVID-19 and myalgic encephalomyelitis/chronic fatigue syndrome. Proc Nat Acad Sci USA 2021;118:e2024358118. https://doi.org/10.1073/pnas.2024358118
  2. Lemle MD. Hypothesis: chronic fatigue syndrome is caused by dysregulation of hydrogen sulfide metabolism. Med Hypotheses 2009;72:108-https://doi.org/10.1016/j.mehy.2008.08.003
Dr. Anthony Komaroff

Anthony Komaroff, MD

Editor in Chief, Harvard Health Letter

Anthony Komaroff is the Steven P. Simcox/Patrick A. Clifford/James H. Higby Professor of Medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital in Boston, and editor in chief of the Harvard Health Letter. He was director of the Division of General Medicine and Primary Care at Brigham and Women’s Hospital for 15 years, and is the founding editor of Journal Watch, a summary medical information newsletter for physicians published by the Massachusetts Medical Society/New England Journal of Medicine.

ME/CFS Research: State of the Art, State of the Science

Written by Dr. Anthony Komaroff

On June 7, 2021, Drs. Lipkin and Komaroff published an article in Trends in Molecular Medicine on the state of ME/CFS research in the wake of COVID-19.

An illness like ME/CFS has been described in the medical literature for several hundred years.  Yet, when interest in the illness resurfaced in the mid-1980s, you could not find any mention of it in the major textbooks of medicine.

There were several reasons for this. First, past medical publications described the symptoms of the illness but did not report underlying biological abnormalities that might be causing those symptoms. Some doctors concluded that if no underlying biological abnormalities had been found, that the illness probably was not “real”. 

Furthermore, when doctors seeing patients with the symptoms of ME/CFS ordered the “standard” laboratory tests in the mid-1980s, the “standard” test results typically were normal. 

Unfortunately, upon receiving the normal test results some doctors told their patients that “there is nothing wrong with you.”  That was one possible conclusion.  Another possible conclusion that those doctors might have considered, but did not, was that they were ordering the wrong tests. Indeed, other tests available to them even in the mid-1980s did find abnormalities in many people with ME/CFS1.

Now, in the 21st century, we have state-of-the-art technologies for identifying underlying biological abnormalities that were unavailable (and even unimaginable) in the mid-1980s.  Most of the testing being performed by the Columbia Center for Solutions for ME/CFS employs these newer technologies.

These are some of the new technologies:

  • We now have much greater power to detect the presence of infectious agents—including previously undiscovered agents—using technologies like polymerase chain reaction (PCR). 
  • Diseases typically occur because the coordinated interaction of multiple different molecules has been disrupted. Most medical research previously measured only one or a few molecules in a blood sample. Today, we can measure literally thousands of molecules in a single sample. That means we can identify molecules that appear to be linked as part of a biological pathway. Once you identify pathways that are linked to a particular disease, the molecules in those pathways become candidates to serve as possible diagnostic tests, and also can become the basis for designing new treatments.  The Center is measuring thousands of different molecules in people with ME/CFS and in healthy control subjects.
  • The molecules the Center is measuring are not just the molecules made by our body. They also include molecules made by the microbes that live on and in our body. One of the great discoveries of the past 20 years has been the recognition that the genes of the microbes that live within us (our microbiome) produce molecules that affect our health. The Center is measuring those microbes, and the molecules they produce.
  • We can measure the structure of all the human genes as well as the microbial genes. That’s important because the purpose of a gene is to make a particular protein, and the structure of the gene determines the structure of the protein. It is the proteins that ultimately make our bodies work—that allow us to move, to see, to think. If there’s something wrong with the structure of a person’s gene, the result can be the production of a defective protein.
  • We also can measure whether a particular gene is activated to make the protein it is supposed to make. That’s important because even if the structure of a gene is perfectly fine, if the gene is not activated when it should be, it can have adverse effects on health.

That’s the remarkable state-of-the-art in biological technologies that can be deployed to study disease in 2021.  What’s the state-of-the-science, regarding ME/CFS?  I and Dr. Ian Lipkin, Director of the Center, have just published an article summarizing the state-of-the science. It was published online in late June 2021, in the journal Trends in Molecular Medicine2. As summarized in more detail in that article, we note that people with ME/CFS have:

  • Larger numbers of inflammation-causing bacteria, and smaller numbers of inflammation-fighting bacteria, in their gut, changes that correlate with symptoms;
  • Higher numbers of activated immune cells called T cells, as if the cells are fighting a battle against something;
  • Depressed function of another type of virus-fighting cell called natural killer (NK) cells;
  • Higher levels of certain chemicals (cytokines) that the immune system uses to fight battles;
  • Various autoantibodies—evidence of an autoimmune process in which the body’s immune system attacks not some foreign invader but attacks parts of the body, itself;
  • An impaired ability to make energy molecules (ATP);
  • Various abnormalities in the brain and autonomic nervous system

Finally, our recent article discusses how the growing knowledge about ME/CFS may affect our understanding of the lingering illness that can occur in people who develop COVID-19—postacute COVID-19 syndrome, or “long COVID”—and vice versa. We also propose a research agenda for both ME/CFS and postacute COVID-19 syndrome. We need to know whether the underlying biological abnormalities of ME/CFS are similar or identical to those in postacute COVID-19 syndrome.  Although we don’t yet know how many people will develop postacute COVID-19 syndrome, it is plausible that the number in the U.S. soon will match the number who already suffer from ME/CFS—as many as 2.5 million people3.

In summary, the recent article summarizes in some detail what is known about the underlying biology of ME/CFS. It also highlights the fact that understanding a disease sometimes awaits the development of new scientific technologies. The article also emphasizes why physicians should never dismiss an illness just because they don’t understand it. With dedication, new tools and an open mind, the answers are coming.

1Bates DW, Buchwald D, Lee J…Komaroff AL. Clinical laboratory test findings in patients with chronic fatigue syndrome.  Arch Intern Med 1995;155:97-103.

2Komaroff AL, Lipkin WI. Insights from myalgic encephalomyelitis/chronic fatigue syndrome may help unravel the pathogenesis of postacute COVID-19 syndrome. Trends Mol Med 2021, published online June, 2021 https://doi.org/10.1016/j.molmed.2021.06.002

3Komaroff AL, Bateman L. Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome?  Front Med 2021;7:606824. doi: 10.3389/fmed.2020.606824

Dr. Anthony Komaroff

Anthony Komaroff, MD

Editor in Chief, Harvard Health Letter

Anthony Komaroff is the Steven P. Simcox/Patrick A. Clifford/James H. Higby Professor of Medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital in Boston, and editor in chief of the Harvard Health Letter. He was director of the Division of General Medicine and Primary Care at Brigham and Women’s Hospital for 15 years, and is the founding editor of Journal Watch, a summary medical information newsletter for physicians published by the Massachusetts Medical Society/New England Journal of Medicine.

A letter from our Community Advisory Committee

Francis S. Collins, M.D., Ph.D.

Director, National Institutes of Health (NIH)

9000 Rockville Pike

Bethesda, Maryland 20892

Dear Dr. Collins,

We are a Community Advisory Committee established with the support of the NIH to advise the ME/CFS Collaborative Research Center consortium. We are housed at the Center for Solutions for ME/CFS at Columbia University. Our committee includes people living with ME/CFS, caregivers, advocates, and representatives from Solve ME/CFS Initiative, Bateman Horne Center, and #MEAction.  

We applaud the NIH’s commitment to research into Post-acute sequelae of SARS-CoV-2 infection (PASC) known as Long COVID. We also wholeheartedly support the letter sent to you by the Long COVID Alliance and join them in all their recommendations.

We believe it would be a lost opportunity to embrace the struggle of people with PASC without also embracing those with Post Viral Fatigue Syndromes and ME/CFS. It is well known that up to 80% of people who have ME/CFS develop the disease following acute infections such as SARS, Ebola and common viruses like EBV, human herpesvirus-6, enteroviruses and others – and even after parasitic and bacterial infections.

Dr. Anthony Fauci, NIAID Director, Dr. Walter Koroshetz, NINDS Director, Dr. Nina Schor, NINDS Deputy Director, and other researchers have recognized that a significant percentage of people with PASC have symptoms “strikingly similar” to ME/CFS. These include post-exertional malaise, cognitive dysfunction, pain and sleep disorders as well as POTS. Individuals with Long COVID are being diagnosed with ME/CFS. Specialist clinician researchers Dr. Anthony Komaroff and Dr. Lucinda Bateman expect the number of people with ME/CFS to at least double due to COVID-19 infections. 

Millions around the world have had their lives destroyed and held hostage by ME/CFS, while being maligned and disenfranchised in the medical and disability systems – as well as dismissed with respect to disease burden in biomedical research. They flounder in a desert of indifference, inappropriate treatment and mis-management with up to 91% undiagnosed. 

In 2017, you wrote that “The NIH is committed to stimulating additional research to reveal the causes of this debilitating disease. ME/CFS is such a complex condition, affecting so many body systems, that we do not know where the answers will come from.” 

There could not be a more compelling opportune moment to stimulate and expedite research into post viral illnesses. Now is the time to push post viral syndrome research alongside this tsunami of PASC illness and disability that is fast becoming a public health crisis. We should build upon the knowledge and understanding from ME/CFS research to advance research in both areas, including utilizing the knowledge of possible harms. 

Therefore, we ask that PASC research prioritize comparator control groups such as people with ME/CFS and other related post-viral illnesses and include ME/CFS researchers and clinicians in strategic planning. This will help to accelerate research and understanding of all post viral illnesses. 

We also strongly request that you, as NIH Director, be inclusive and talk about all post viral fatigue syndromes including ME/CFS and PASC together in future communications and media. In addition, please revise your 2021 blog on Long COVID to be consistent with Dr. Schor and Dr. Koroshetz’s recent public statements articulating the relationship between PASC, PVFS and ME/CFS.

This is an unprecedented time and you are in a unique position to provide leadership in unravelling PASC and associated illnesses. Millions need your support and your voice. Thank you.

Sincerely, 

The Community Advisory Committee for the NIH Collaborative Research Centers

CC:

Anthony S. Fauci, M.D., Director of National Institute of Allergy and Infectious Diseases (NIAID)

Walter J. Koroshetz, M.D., Director of National Institute of Neurological Disorders and Stroke (NINDS)

Nina Schor, M.D., Ph.D., Deputy Director, NINDS

Steven M. Holland, M.D., Director, Division of Intramural Research NIAID

Avindra Nath, M.D., Clinical Director, Division of Intramural Research NINDS

Matthew J. Fenton, Ph.D. Director, Division of Extramural Activities NIAID

Vicky Whittemore, Ph.D. Program Director NINDS

Joseph J. Breen, Ph.D., Section Chief NIAID

Amy Patterson, M.D., Deputy Director for Clinical Research and Strategic Initiatives, NHLBI 


CfS for ME/CFS Drs. Komaroff and Bateman participate in MEAction Presser

On March 25, #MEAction hosted a telepresser featuring a panel of experts uniquely positioned to speak to how long COVID is being informed by the research on myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

Long haulers are overwhelmingly reporting symptoms that resemble ME/CFS at six months, and researchers are expecting the number of people with ME/CFS to more than double during the pandemic, which follows the pattern of past viral outbreaks. Dr. Anthony Fauci has warned repeatedly of the risk for COVID-19 patients to develop ME/CFS.

Our panel of experts knew this was coming, and have dedicated a large part of their careers preparing for this moment. Since the beginning of the pandemic, ME/CFS researchers and clinicians expected that a worldwide viral outbreak would lead to a massive surge in chronic illnesses, including ME/CFS.

  • Dr. Lucinda Bateman, MD, founder of the Bateman Horne Center, is seeing overlapping symptoms in both her long COVID and ME/CFS patients.
  • Dr. Anthony Komaroff, MD oversees the Columbia University – Center for Solutions for ME/CFS Long-COVID study with the Bateman Horne Center. He chaired the Neurology section of the NIH Conference on Post-COVID health complications this past December. In his Frontiers article exploring how past viral outbreaks have led to surges of chronic illness, he estimates COVID-19 will double the number of people with ME/CFS.
  • NINDS Clinical Director, Dr. Avindra Nath, MD, has launched two intramural studies at the NIH to investigate long COVID, which follows on the heels of the institute’s intramural work investigating ME/CFS. Both studies are showing overlapping findings and symptoms.
  • A long hauler and person with ME/CFS will share their experiences of getting a virus and not recovering.

Links:

Read more on the connection between long COVID and ME/CFS:

Long COVID & ME: Understanding the Connection

Studies and articles on post-viral illness:

● https://www.frontiersin.org/articles/10.3389/fmed.2020.606824/full

● https://www.tandfonline.com/doi/full/10.1080/21641846.2020.1778227

● https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889402/

Preprint survey on characterization of long COVID:
● https://www.medrxiv.org/content/10.1101/2020.12.24.20248802v2

Read about the disease burden and historic underinvestment of ME/CFS:
● https://oatext.com/Estimating-the-disease-burden-of-MECFS-in-the-United-States-and-its-relation-to-research-funding.php

Bridging the Gap: Outreach and Engagement with the ME/CFS Community

We are excited to announce the launch of the ME/CFS Collaborative Research Center’s outreach and engagement initiative led by the Center for Solutions for ME/CFS at Columbia University.

The cornerstone of this effort is the establishment of a Community Advisory Committee (CAC) to partner with the NIH Clinical Research Centers (CRCs) at Columbia University, Cornell University, The Jackson Laboratory, the Interdisciplinary Canadian Collaborative Myalgic Encephalomyelitis (ICanCME) Research Network, and the Data Management Coordinating Center at RTI International. The CAC is comprised of 14 individuals including people living with ME/CFS, caregivers, advocates, and representatives from #MEAction and Solve ME/CFS Initiative. We at the Center for Solutions for ME/CFS at Columbia University will serve as the bridge between all stakeholders by coordinating the effort.

The CAC has designated working groups based on the needs of the community as well as the Collaborative Research Centers (CRCs). The initial working groups will focus on information dissemination to address communication matters, study feasibility to aid in clinical study design, and scientific priorities to develop recommendations for future ME/CFS research pathways. The goals of the CAC will be to increase communication, research participation, and accelerate the pace of research.

To complement this work, we have also created the Center for Solutions for ME/CFS Communications Hub, which is comprised of representatives from nine network-affiliated organizations. The Hub encourages cross-promotion and amplifies the distribution of network developments and findings. Our cooperative effort ensures the timely distribution of information and significantly broadens the reach to ME/CFS stakeholders.

For more information on the launch of the ME/CFS Collaborative Research Center’s outreach and engagement initiative, tune into the NIH’s ME/CFS Working Group Call this upcoming Thursday, November 5 at 11AM ET.

Click the link below to join the webinar:

https://nih.zoomgov.com/j/1608562314?pwd=Ny92SU81SFdJV1ZTL0I1WFUwalVjdz09

Passcode: MECFS2020

Center for Solutions Community Engagement and Outreach Team

Allison Kanas

Director, Community Outreach and Engagement

Sydney Silverman

Manager, Community Outreach and Engagement

CRC Community Advisory Committee

Amy Williams

BA Occupational Therapy

Microbe Discovery Project

Person living with ME/CFS

Angela Linford

Bateman Horne Center

Angela is the Communication Director at Bateman Horne Center (BHC). She has a bachelor’s degree in organizational communication from the University of Utah. After spending 10 years managing public involvement for Utah Department of Transportation projects her ME/CFS progressed to the point that she was forced to leave her career and receive care from a family member for several years. Angela served on the BHC Board of Directors (formerly OFFER) for 10 years before taking on her current role. Having experienced the medical system’s lack of understanding about ME/CFS before connecting with a knowledgeable and experienced provider, she is passionate about provider and patient education.  

Cherylle McFarlane, RN

Challenged with ME/CFS

Cherylle has been an RN for 30 years. She holds a MHA and is a Certified Life Coach. Cherylle is passionate about health, advocacy, education, alternative medicine and bridging the gap between Eastern and Western medicine. After seeking help for 21 years, in 2014, she was officially diagnosed with ME/CFS and Arnold Chiari Malformation, a brain defect linked to ME/CFS. During recovery from brain surgery in 2019, Cherylle published a children’s book “Mommy Wants to Feel Better” to initiate conversations for families dealing with family members challenged with chronic illnesses. She also has an inspirational Podcast called “Just Praying”.

Emily Taylor

Solve M.E.

Emily has over fifteen years of policy, organization, and advocacy experience in both the non-profit and government sectors. With five years experience on Capitol Hill, Emily contributes a keen understanding of both state and federal policy processes while cultivating strong grassroots organization and patient representation. Prior to joining the Solve ME/CFS Initiative, Emily served as the director of policy and advocacy for an autism organization. There she spearheaded major overhauls in disability, early intervention, and education policies. She is also a veteran of several successful electoral campaigns, where she trained others in effective social media and online organization. She received a B.A. with honors in politics and international relations from Scripps College in Claremont and earned her M.A. in American politics from Claremont Graduate University. Emily draws inspiration from her mother who has battled ME/CFS as well as chronic autoimmune and thyroid conditions since 1999.

Jaime Seltzer

#MEAction

Jaime is the Director of Scientific and Medical Outreach at #MEAction. She is responsible for fostering communication between research scientists, clinicians, and people with myalgic encephalomyelitis. She has represented #MEAction at CDC, NIH, Capitol Hill, Columbia University (Collaborative Research Centers), and Stanford University; and she has been the invited author and/or committee member for national healthcare organizations CIHR (Canada), Office of Health Protection (Australia), National Institutes for Health Care (UK) and NIH. She works as a research consultant to Stanford University’s Stanford Genome Technology Center on ME/CFS-related projects.

Jessie Brown-Clark

Solve M.E.

Jessie is the Engagement Coordinator at Solve ME/CFS Initiative. She has a bachelor’s degree in psychology from Pepperdine University where she also studied non-profit management. Before joining Solve M.E., she served as an educational advocate for students with disabilities and the coordinator for a children’s literacy organization. She is passionate about advocating for access to healthcare, information, and support for the ME/CFS Community.

Kathi Kuehnel, J.D.

ME/CFS Caregiver

Kathi is a lawyer in Michigan. She retired from the auto industry, having held director level positions at Ford in the Chairman’s office, Dealer Policy Board (alternative dispute resolution), and State and Local Government. She has worked as an electron microscopist, and has a passion for evolutionary biology and genetics. She holds a B.A. (highest distinction) from Northwestern University in Biology and Anthropology, a J.D. from Cornell University School of Law with a specialty in Science, Technology and Law and a Professional Certificate, Harvard Kennedy School of Government-State and Local Government. She is active in environmental organizations and is the mother of a daughter with ME/CFS.

Mary Dimmock

ME/CFS Caregiver and Patient Advocate

Mary worked at Pfizer for 31 years in roles that spanned drugmetabolism research, clinical data management and database administration, development of R&D information systems, and R&D business process improvement and integration. She retired in 2011 when her son became ill with ME. Since then, she has worked on a number of US and international advocacy initiatives to advance research and improve clinical care for people with ME. More recently, Mary has partnered with Dr. Lucinda Bateman of Bateman Horne Center to organize the US ME/CFS Clinician Coalition and its annual Summit, now in its third year. Mary is passionate about finding ways to accelerate research and the delivery of treatments to patients and to broaden the research.

Neal Goldberg, PhD

Neal holds a doctorate in Psychology from Fordham University with post-doctorate training in both child/adolescent and adult psychotherapy. Neal is a passionate proponent of healing through laughter and empowerment through joy. He founded and is the Executive Director of Lev Leytzan: The Heart of Therapeutic Clowning, Inc. Neal collaborated with Open Medicine Foundation to launch Hope & Heart, an initiative to build international awareness for ME/CFS. The campaign elicited poems and art submissions from people in 17 countries. In addition to the poem and art contributions, the campaign culminated with an original song, “Keeping the Hope,” used an anthem for many with ME/CFS. His awareness of ME/CFS began five years ago when his child had become progressively more ill from this debilitating disease. The difficulty in his child receiving a diagnosis, the little scientifically known by doctors about the disease, and limited resources available to patients led him to become more involved by becoming a liaison between those suffering and the medical community.

Nina Muirhead, BMBCh MEd

Chair Education Group, CMRC

Forward ME, UK

Individual Living with ME/CFS

Miss Nina Muirhead is a Dermatology Surgeon working in the UK National Health Service. She qualified in Oxford and is a member of the Royal College of Surgeons, she has a Masters Degree in Medical Education. She is a Director of Doctors with ME, Chair of the CMRC Education Working Group, Member of Forward ME and an active member of education working groups within CDS and ICanCME. She has personal lived experience of ME/CFS following EBV glandular fever (mononucleosis) in 2016, for at least 6 months she was severely affected and is now mildly affected. She works part time as a doctor and has established international connections with ME/CFS researchers and clinicians.

Rochelle Joslyn, PhD.

Rochelle has a PhD in Immunology and over a decade of experience working as a scientist in human biomedical research. After developing ME/CFS in 2004 and seeing the immense need for scientific breakthroughs to transform poor medical care, she pursued a research career during intermittent remissions in her disease. Rochelle participates broadly in the ME/CFS scientific and advocacy communities, volunteering with many institutions, organizations, and individuals to drive progress for the disease on many fronts, largely behind the scenes. She has served in many patient and scientific advisory roles, bridging the gap between the lived experience of ME/CFS and its scientific inquiry. Having experienced the devastation of this disease, she is driven to do everything she can to move the ball forward for people living with ME/CFS, from informing scientific study designs to combatting medical stigma to federal advocacy.

Sabrina Poirer

ICanCME Research Network

Patient Partner in Research

Individual Living with ME/CFS

Sabrina has worked within the private, public and not-for-profit sectors for over 20 years. Her work in politics, education and community development helped shape her perspective and fine tune her approach to meaningful engagement and positive systems change. In addition to her role with the CAC, she also serves as a member of the ICanCME Steering Committee, the Chair of the ICanCME Trainee Development/Medical Education Working Group and as a passionate patient advocate. She also served as a Patient Engagement Research Ambassador for CIHR’s IMHA Institute from 2018-2021. Sabrina uses her passion, skills and personal experience as an individual living with ME (and common comorbidities), in the fight to have the illness understood, researched and removed from the shadows once and for all. She’s very thankful for the opportunity to learn from, and collaborate with, others on the CAC.

Susan Taylor-Brown

Susan is a retired professor of Pediatrics and Social Work whose career focused on healthcare with an emphasis on the impact of HIV/AIDS on women and children, intellectual/developmental disabilities and family-centered care. She taught graduate and undergraduate students from diverse professions and maintained an active clinical practice during my academic career. As a pwME, she faced challenges obtaining a ME diagnosis (>5 years), appropriate care (treatment denial by insurance), in addition to the stigma that comes along with the illness. She is committed to improving the dissemination of scientific ME knowledge, decreasing the stigma experienced by patients, along with expanding access to diagnosis and treatment, particularly for people of color (POC), who are disproportionately affected by ME and are currently underrepresented in individuals receiving ME care.

Tahlia Ruschioni

Bateman Horne Center

Tahlia has over fifteen years’ experience working in a variety of healthcare settings. After graduating with her degree in exercise science, she worked as the lead rehabilitation specialist at a local Level II trauma center. Once in Salt Lake City, UT, she worked for the University of Utah Health creating and disseminating health education to a network of twenty-five affiliated hospitals and clinics spread throughout seven surrounding states. It was in this role, that she was introduced to the work of Dr. Lucinda Bateman, and began to find commonalities in what Dr. Bateman was teaching and that of her father and sister’s unexplained illnesses. In an attempt to learn more and find answers for her family, her profession and personal life merged, findings its beginnings as the Education Director at the Bateman Horne Center, where she strives to increase awareness and education on ME/CFS, FM, and related comorbid conditions.

Therese Russo, MPA

ME/CFS Patient Advocate

Individual Living with ME/CFS

Therese is an ME and health justice activist based in Brooklyn, NY. She is currently a volunteer lead with #MEAction’s federal advocacy team. Before becoming too sick to work full-time, she was the senior health equity programs analyst at NYC Health + Hospitals’ Corporate Office of Diversity and Inclusion. She holds a Master of Public Administration in health policy analysis from NYU Wagner School of Public Service, where she contributed to research on the effects of the Affordable Care Act’s Medicaid expansion on out-of-pocket healthcare spending. She joined this committee to help build communication channels between people with ME and researchers, as she believes patient engagement is critical for effective research.

A Proteomics Study from the Center: Searching for the Criminal

By Dr. Anthony Komaroff

On July 21, 2020, the results of a proteomics study by the Center for Solutions for ME/CFS was published by the journal PLoS ONE.

Proteomics uses new technologies—that have become available in the last two decades—to precisely identify large numbers of proteins and measure their levels. The measurement is made in some compartment of the body: the blood, the spinal fluid, a particular organ, even within a single cell. These new technologies make it possible to take a sample from the compartment, like a small sample of blood, and to accurately measure the levels of hundreds, even thousands, of different proteins in that sample, relatively inexpensively and rapidly.

In the “old days”—way back in the 20th Century—scientists often had to be content with measuring the levels of one protein at a time. Since proteins typically interact with large numbers of other proteins and other types of molecules, you often didn’t learn much by measuring one protein at a time. A great strength of the Columbia Center for Infection and Immunity, where the Center for Solutions for ME/CFS is housed, and its collaborating facility at the University of Pennsylvania – Epigenetics Institute, is the ability to measure large numbers of molecules at the same time, and to study how they interact.

What did the latest study from the Center show? Basically, two things:

  • There appears to be a distinctive “signature” of a small group of proteins that distinguishes people with ME/CFS from healthy people;
  • The proteins involved in that “signature” are primarily involved in the immune response—particularly the response of immune cells called B cells—to infections, and the response seen in autoimmune diseases.

It is possible that the “signature” that has been found might some day become a diagnostic test for ME/CFS. A perfect diagnostic test for a disease (in this case, ME/CFS) has two essential elements:

  • It must have no “false negatives”: the test result can never be negative (“normal”) in a person who really does have the disease.
  • It must have no “false positives”: the test result can never be positive (“abnormal”) in a person who does not really have the disease.

There are very few perfect diagnostic tests in medicine, but there are many that come pretty close to perfection. For the signature that the Center’s study has identified to become a diagnostic test it will need to be tested again:

  • In larger numbers of people with ME/CFS from all over the world to determine whether the test has a very low false negative rate;
  • In large numbers of people with diseases other than ME/CFS that also can cause the hallmark symptoms of ME/CFS—fatigue, post-exertional malaise, unrefreshing sleep, cognitive impairment, orthostatic intolerance—to determine whether the test has a very low false positive rate in those diseases.

The new study is consistent with prior studies that have found abnormalities related to B cells in people with ME/CFS. B cells are white blood cells, also called lymphocytes, that are important in the response of the immune system to foreign invaders, like infectious agents. In particular, B cells ultimately lead to the production of antibodies—antibodies to fight infectious agents, and auto-antibodies that are seen in autoimmune diseases.

Does this study have implications for treatment?

The study—like most studies—seeks to identify what is going wrong in the body of people with this illness. The reason for this is not just because the answer might be interesting, but because the answer might provide a target to shoot at with a treatment.

In this case, the study may prompt scientists to test more ways to quiet overactive B cells (some past attempts have failed), particularly the production of autoantibodies. Also, if further studies can identify the antigens that the activated immune system is activated by, these results may reveal underlying toxins, infectious agents, or other foreign molecules that can themselves be targeted .

Medical researchers sometimes are called “disease detectives.” If you think of research as detective work, then the cause of a disease is the criminal. This research has not definitively found the criminal that causes ME/CFS, but the research does strongly suggest the neighborhood where the criminal is likely to be hiding.

Authors: Milivojevic M, Che X, Bateman L, Cheng A, Garcia BA, Hornig M, Huber M, Klimas NG, Lee B, Lee H, Levine S, Montoya JG, Peterson DL, Komaroff AL, Lipkin WI. Title: Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS.

Journal citation: PLoS ONE 15(7): e0236148. https://doi.org/10.1371/journal.pone.0236148

Dr. Anthony Komaroff

Anthony Komaroff, MD

Editor in Chief, Harvard Health Letter

Anthony Komaroff is the Steven P. Simcox/Patrick A. Clifford/James H. Higby Professor of Medicine at Harvard Medical School, senior physician at Brigham and Women’s Hospital in Boston, and editor in chief of the Harvard Health Letter. He was director of the Division of General Medicine and Primary Care at Brigham and Women’s Hospital for 15 years, and is the founding editor of Journal Watch, a summary medical information newsletter for physicians published by the Massachusetts Medical Society/New England Journal of Medicine.