Why Can’t Anthony Komaroff Stop Harming ME/CFS Patients?

Breaking News for ME/CFS patients: You’re not sick, you’re “hunkering down”

During the first half of 2023, veteran ME/CFS researcher Anthony Komaroff at the Harvard School of Medicine was senior author on two publications that not only did nothing to clarify anything about the syndrome, but also injected more uncertainty, blurring the edges between ME/CFS and other conditions, and did nothing to help patients.

A review article by Komaroff and coauthor Ian Lipkin—another experienced ME/CFS researcher at the Columbia Mailman School of Public Health—summarized the similarity of symptoms and “biological abnormalities” between ME/CFS and Long Covid. (1)

Their review article examined 21 previous research reports. “Moreover, we show that the two illnesses [ME/CFS and Long Covid] share many of these underlying abnormalities, just as they share many symptoms. That is, both illnesses are ‘real,’ and both share similar biological abnormalities,” Komaroff and Lipkin state.

As for Long Covid, they point out that “The illness has been given several names, including post-acute SARS-CoV-2 sequelae (PASC), post-COVID-19 condition (PCC), post-acute COVID-19 syndrome (PACS), and ‘Long COVID’—the name we use in this review. We distinguish it from other post-COVID conditions in Table 1, below.”

Table 1 describes “Long Covid”:

Long COVID: a group of persisting symptoms that interfere with the
ability to function at home or at work, are not explained by major
organ injury (e.g., pulmonary fibrosis, cardiomyopathy, cerebral
infarction, kidney failure). These symptoms include fatigue, cognitive
problems, headaches, disrupted sleep, myalgias and arthralgias,
post-exertional malaise, orthostatic intolerance, tachyarrhythmias and
gastrointestinal complaints such as diarrhea. Although there is no
major organ injury, there are some underlying biological abnormalities
which are summarized in this review. People with Long COVID often
are referred to as "long haulers.” (1)

When comparing ME/CFS to Long Covid, Komaroff and Lipkin point out, “Early in the study of both illnesses, the lack of objective biomarkers led some to question whether the illnesses were ‘real’—whether people might be imagining or even fabricating their symptoms.”

Long Covid is “real” enough that “nearly 2% of the total civilian labor force is unable to work” because of it, with a loss in wages of “$170–230 billion annually,” Komaroff and Lipkin report.

“Because of the exceptional anticipated burden,” they continued, “the National Institutes of Health has dedicated over $1 billion in support of studies of the underlying biology and natural history of various post-COVID conditions.”

Komaroff and Lipkin state that “interest in ME/CFS (originally called ‘Chronic Fatigue Syndrome’) surged in the mid-1980s,” failing to note the outbreaks that occurred during that decade. They provide their description of ME/CFS:

Myalgic encephalomyelitis/CFS often, but not always, follows in the
wake of an apparent “infectious-like” illness characterized by respiratory
and gastrointestinal symptoms, fatigue, myalgias and other symptoms
as well as fever and lymphadenopathy. This “infectious-like” illness
often is little different, initially, from the common, transient infectious
illnesses that most people experience throughout life. It is not standard
medical practice to test for the responsible infectious agent in people
with common and transient infectious illnesses. Thus, typically no testing
has been done to determine the cause of the initial “infectious-like”
illness that then becomes a chronic illness in subsequent months and
years. (1)

This convenient—though created out of whole cloth—excuse for not searching for a cause of ME/CFS not only basically rules out ever finding a cure, but also pre-empts research into contagion:

“Although in this review we are describing cases of ME/CFS that occur sporadically, there also have been apparent epidemics of a similar illness described in communities and in large hospitals over the past century,” they continue. “In one report, 6% of a community of 2,500 people—most young or middle-aged adults—became suddenly ill with an infectious-like illness followed by at least 5 months of a cyclic, debilitating illness characterized by fatigue, cognitive impairment (confirmed on objective testing) and pain. Details on symptoms, physical examination findings and laboratory test results in these studies are not sufficient to determine how similar these illnesses were to ME/CFS.”

Then a feeble justification for not searching out an infectious agent is offered:  “Attempts to identify a single and possibly novel infectious agent as the cause of most cases of ME/CFS have been unsuccessful. For example, claims that murine leukemia viruses cause ME/CFS have been refuted, as have similar claims for Borna disease virus.” (2)

But wait—these two conditions, ME/CFS and Long Covid, might not represent discrete entities at all:

“Not only is a common core of symptoms shared by ME/CFS and Long COVID: these same symptoms also are also reported following multiple infectious illnesses and major non-infectious injury such as post-critical illness syndrome or post-intensive care unit syndrome, including heat stroke.” (1)

Really, Drs. Komaroff and Lipkin? Thirty-five years later, you’re comparing ME/CFS to heat stroke?

They go even further, suggesting that ME/CFS and Long Covid’s common symptoms and biological abnormalities might be a response in humans similar to hibernation in “higher animals” (not to mention a possible association with worm larvae):

Such a carefully orchestrated response to vital threats exists throughout
the animal kingdom. The best studied examples are hibernation and
torpor in “higher” animals, and the larval state of dauer in the worm
C. elegans.

Dauer, hibernation and torpor all involve “abnormal” innate immune
responses, redox imbalance, increased glycolysis, decreased aerobic
respiration, and possibly even alteration in the organisms’ microbiome.
They also involve orchestration by the autonomic nervous system (and
its counterparts in the nervous systems of more primitive organisms).
Thus, these well-recognized “hunkering down” mechanisms all exhibit
similarities to the emerging pathophysiology of ME/CFS and Long
COVID, as summarized in this review. (1)

Why compare ME/CFS and Long Covid when you think that one has no viral cause and the other has an accepted viral cause? What’s the point, other than to muddy the thinking around both illnesses?

And if Long Covid is so similar to ME/CFS, why aren’t these veteran ME/CFS researchers urging other scientists to search for the viral cause of ME/CFS?

Like all reviews, this one provides hundreds of data points in numerous tables, and I recommend reading the paper if you’re interested in that level of minutia. While it may be extremely helpful to other academics, it really doesn’t add much to a discussion of how similar ME/CFS and Long Covid are to each other. Does it help patients? No, and here’s why:

1.     In Long Covid, there is an identified infectious agent, and
2.     most Long Covid patients know precisely when they became ill.
3.     ME/CFS patients have neither an identified viral cause nor a good idea about when they first became ill. Is it really helpful to compare a patient who’s had ME/CFS for ten years to a Long Covid patient who has been sick for two years or less?

This review’s main takeaway is that these two groups of very sick patients who need help—an effective treatment, perhaps?—are, at best, being jerked around by the scientific and medical establishments.

Komaroff’s other 2023 research report—along with two faculty members from the University of Massachusetts and one from the Harvard School of Public Health—attempts to differentiate the risk factors for ME/CFS from those for “Severe Fatigue,” which primarily affects the elderly and/or gravely ill. (2)

Funding for the ME/CFS v. Severe Fatigue study was provided from: the Chronic Fatigue Initiative (CFI) of the Hutchins Family Foundation; U.S. National Institutes of Health (U01 CA176726) to the Nurses’ Health Study II; the National Institutes of Health (R01NS097723) to coauthor Natalia Palacios at the UMass Life Sciences Center; the US subsidiary of the Japanese company Esai Pharmaceuticals; and a US Public Health Service Grant (AI138370) to Anthony L. Komaroff.

Leading to two more questions:
1.     Why did NIH and other agencies fund this study?
2.     Why did Nature waste the paper it was printed on?

The stated purpose of this study was “To determine if ME/CFS is just a more extreme form of fatigue, or a qualitatively different condition”; to accomplish this, the team “assessed whether risk factors for ME/CFS and for Severe Fatigue were similar.” (2)

The conclusion: “The different contribution of various risk factors to Severe Fatigue and ME/CFS suggests that ME/CFS has a qualitatively different underlying biology from the more common state of Severe Fatigue.” (2)

This conclusion—in fact, the whole paper—is inexplicable, given that most current research into ME/CFS no longer considers fatigue its defining factor.

While Long Covid and Severe Fatigue are terrible conditions and deserve much more serious research than given in the described published papers, let’s instead compare ME/CFS to a deadly serious illness: AIDS.

And let’s look at the early days, before causality and all other parameters were set in stone, when physicians and scientists were making firsthand observations.

First, let’s examine the symptoms first described for AIDS and ME/CFS, both of which emerged in the late 1970s (according to most conventional reports).

AIDS/ARC Symptoms: A 1987 collection of research reports about AIDS described the symptoms associated with “ARC” (AIDS-Related Complex), at that time believed to be a separate entity that might or might not progress to AIDS. Symptoms associated with both ARC and AIDS included fever, lymphadenopathy (swollen lymph nodes), night sweats, weight loss, diarrhea, loss of T-4 (CD4) cells, cellular immune deficiency, “unexpected” cancers (including Kaposi’s sarcoma, Burkitt lymphoma and others), and cognitive dysfunction or dementia. (4,5)

ME/CFS Symptoms: A 1987 paper describing the symptoms seen in the Lake Tahoe outbreak reported fever, lymphadenopathy (swollen lymph nodes), chronic fatigue, and sore throat. (6) A contemporaneous paper included symptoms of night sweats, diarrhea, fatigue, depression, muscle pain, and anxiety. (7)

AIDS/ARC Viruses: A new virus was isolated from AIDS patients in 1986—Human B-Lymphotropic virus or HBLV. (8)  AIDS and ARC patients were also found to be infected with HTLV-III/LAV, which was renamed HIV after a lawsuit between the US and France over the virus’s discovery. These patients also had high levels of antibodies to Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes zoster, as well as frequent candidiasis (a fungal infection). (5)

ME/CFS Viruses: ME/CFS patients were lucky to be tested for any infectious agent in 1987, but those who were showed high antibody titers to EBV (8) and they, too, were found to harbor the new HBLV, since renamed Human Herpesvirus-6 (HHV-6). Incline Village physician Paul Cheney also reported candidiasis (a fungal infection) among his patients. (8,9)

And strangely, the numbers of patients with each syndrome (AIDS and ME/CFS) have remained stable for 30-plus years.

AIDS Stats: In 1987, some of the very first AIDS researchers wrote, “It is now thought that at least one million persons in the United States are infected with HTLV-III and have the potential to develop AIDS.” (10) In 2022, HIV.gov stated “Approximately 1.2 million people in the U.S.A. have HIV. About 13 percent of them don't know it and need testing.” (11)

ME/CFS Stats: In 1990, German professor G.R.F. Kreuger suggested there were already at least one million cases of ME/CFS in the US on the late Pat Robertson’s 700 Club Show (Christian Broadcasting Network). The National Cancer Institute’s Dr. Dharam Ablashi and New York pediatrician Dr. David S. Bell were also interviewed on the show about their evidence that the new syndrome was not only caused by a virus but also was, in their opinions, infectious. In 2021, the CDC estimated that “836,000 to 2.5 million Americans have ME/CFS. At least one-quarter of individuals with ME/CFS are bedbound or housebound at some point in the disease and most never regain their pre-disease level of functioning.” (12)

At the very least, the comparison of ME/CFS and AIDS shows that ME/CFS should, by virtue of the estimate of how many people have the illness—which can’t really be determined because of the lack of a reliable test of any kind, 35 years later—receive at least as much federal research funding as AIDS and certainly as much as Long Covid, which seems like it should be studied as a separate entity.

Perhaps if many ME/CFS researchers weren’t themselves hunkering down but instead designing forward looking studies to provide some insight into this long-abandoned disease, they would do some good for long-suffering ME/CFS patients everywhere.

BIBLIOGRAPHY
1.     Anthony L. Komaroff and W. Ian Lipkin; “ME/CFS and Long Covid Share Similar Symptoms and Biological Abnormalities: Road Map to the Literature”; Front. Med., 02 June 2023. https://doi.org/10.3389/fmed.2023.1187163
2.     Natalia Palacios, Samantha Molsberry, Kathryn C. Fitzgerald and Anthony L. Komaroff; “Different Risk Factors Distinguish Myalgic Encephalomyelitis/Chronic Fatigue Syndrome From Severe Fatigue”; Nature 13:2469, 11 February 2023. https://doi.org/10.3389/fmed.2023.1187163
3.     Institute of Medicine. “Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.” Washington, DC: The National Academies Press (2015).
4.     David R. Rubinow and Russell T. Joffe; “Psychiatric and Psychosocial Aspects of AIDS”; Page 123 in AIDS: Modern Concepts and Therapeutic Challenges, edited by Samuel Broder, Marcel Dekker Inc., 1987.
5.     Jerome E. Groopman; “Spectrum of HTLV-III Infection”; Page 336 in AIDS: Modern Concepts and Therapeutic Challenges, edited by Samuel Broder, Marcel Dekker Inc., 1987.
6.     Gary P. Holmes, et al.; “A Cluster of Patients with a Chronic Mononucleosis-type Syndrome. Is Epstein-Barr Virus the Cause?” Journal of the American Medical Association 257:2297, 1987.
7.     G.R.F. Kreuger, B. Koch, D. Ablashi. “Persistent Fatigue and Depression in a Patient with Antibody to Human B-Lymphotropic Virus.” The Lancet, July 4, 1987.
8.     S.Z. Salahuddin, D.V. Ablashi, P.D. Markham, et al. “Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders”; Science, 234: 596-601, 1986.
9.     Deborah Barnes; “Mystery Disease at Lake Tahoe Challenges Virologists and Clinicians”; Science 234; “Research News,” October 1986.
10.  Robert Yarchoan and Samuel Broder. “Strategies for the Pharmacological Intervention against HTLV-III/LAV.” Page 336 in AIDS: Modern Concepts and Therapeutic Challenges, edited by Samuel Broder, Marcel Dekker Inc, 1987.
11.  “US Statistics,” HIV.gov, updated October 27, 2022. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics/
12.  “About ME/CFS.” National Institutes of Health, updated August 12, 2022. https://www.nih.gov/mecfs/about-mecfs#:~:text=According%20to%20the%20CDC%20%2C%20836%2C000,pre%2Ddisease%20level%20of%20functioning.

ABOUT THE AUTHOR
          Neenyah Ostrom was the first reporter in the United States to report weekly for a decade on ME/CFS. Her reporting on the Chronic Fatigue Syn­drome epidemic from 1988-1997 is getting increased atten­tion thanks to Robert F. Kennedy Jr.  He discusses her work exten­sively in his 2022 best seller, The Real Anthony Fauci. Ostrom’s groundbreaking reporting on Chronic Fatigue Syn­drome and AIDS appeared in the New York Native from 1988 to 1997.
          Ostrom wrote the Foreword to the recently published THE REAL AIDS EPIDEMIC: How the Tragic HIV Mistake Threatens Us All by Rebecca Culshaw, Ph.D.
          Ostrom is the author of four books about the Chronic Fatigue Syndrome epidemic: What Really Killed Gilda Radner? Frontline Reports On The Chronic Fatigue Syndrome Epidemic (1991; TNM Inc., New York, NY), 50 Things Everyone Should Know About The Chronic Fatigue Syndrome Epidemic And Its Link To AIDS (1992; TNM Inc. and St. Martin’s Press, New York, NY; published in Japanese by Shindan-to-Chiryo, 1993; and in French by Les Edi­tions Logiques, 1994), and America’s Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syn­drome Epidemic And Its Link To AIDS (1993; TNM Inc., New York, NY); and America’s Biggest Cover-Up: 50 More Things Everyone Should Know About The Chronic Fatigue Syn­drome Epidemic And Its Link To AIDS, Updated 2^nd Edition (2022, available as a Kindle ebook and paperback on Amazon.com). Her most recent book, Ampligen: The Battle for a Promising ME/CFS Drug (2022) is available as a Kindle ebook and paperback on Amazon.com
          In 1995, Ostrom and New York Native were rec­ognized as having reported one of the top 25 most-censored stories in the U.S. press by 1995’s Censored: The News That Didn’t Make The News And Why (The 1995 Project Censored Yearbook by Sonoma State University Professor Carl Jensen, introduction by Michael Crichton; pub­lished by Four Walls Eight Win­dows, New York, NY, 1995).
          Ostrom is ghostwriter/editor of seven popular science books. Additionally, she was an editor of Total Breast Health: The Power Food Solution For Health And Wellness by Robin Keuneke, which was chosen as a Publishers Weekly “Best Book of 1998” in the category of Breast Health (Kensing­ton Publishing Corp., April 1998).