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By David Tuller, DrPH

Earlier this week, I blogged about a story in The Observer that provided an inaccurate description of what it called chronic fatigue syndrome. For much of the piece, the writer, Eleanor Morgan, offered a sympathetic portrait of people, including herself, experiencing prolonged symptoms after an acute bout of Covid-19. A lot of what she presented was informative and likely helpful for others in that situation.

Unfortunately, as I noted, Morgan got it wrong when she turned to CFS. For this section, she appears to have relied on one set of sources–in particular, those who style themselves biopsychosocialists. And maybe because these biopsychosocial sources were speaking within their presumed field of authority, she did not dig deeper in order to present the more complicated reality—that the theoretical framework she highlighted has been seriously challenged in recent years and is now in threat of collapse.

This ongoing shift broke into public view last month when the National Institute for Health and Care Excellence (NICE) released the draft of its new ME/CFS clinical guidelines, which repudiate the long-standing psychiatric hypotheses governing the national approach to the illness. The NICE announcement was widely covered in the UK, including in  The TimesThe Telegraph, The Guardian and BMJ.com. (In the US, STAT, ran a piece I co-wrote with Northwestern University law professor Steven Lubet.)

Sunday’s Observer article immediately came under criticism—including (obviously) from me. But I want to stress that this is just one article, from a writer (an excellent writer, judging from this example) who is suffering from perplexing symptoms and struggling to figure out what she and others in a similar plight should do. Morgan’s piece has received an onslaught of attention, and many of the tweets and comments have probably been difficult to read. In my many years as a journalist, I have definitely gotten things wrong. And at times it took some time to absorb strong critiques, get beyond my defensive posture, and reassess what I’d written.

So again—this is one article, to be followed quickly by others. And today, sure enough, The Guardian published its own piece on prolonged post-Covid symptoms–a well-reported column called “Is long Covid contagious and can children get it?: your questions answered.” (The Guardian and The Observer have corporate links while being editorially separate.)

In this new article, Linda Geddes, a Guardian science correspondent, addresses the relationship between ME/CFS and long-Covid in a manner more aligned with biomedical reality than with unproven psychiatric theorizing about how patients “compound” their fatigue by “catastrophizing” it. This follows a November piece by Geddes called “Long Covid: overlap emerges with ME – including debate over treatment,” which was an impressively nuanced account of the current situation.

In today’s piece, Geddes quotes both Charles Shepherd, medical adviser to the ME Association, and William Weir, an infectious disease physician who has long been an advocate for appropriate patient care. Geddes had also reached out to me a few weeks ago. We exchanged e-mails and I promised to answer her at greater length. This morning, while reviewing our correspondence, I discovered that a further response I thought I’d sent with various information and links remained in draft form, undispatched!

Oops! Sorry, Linda!!

*******

Paradigm as obstacle

In fact, the main obstacle to change has not been an individual writer or an individual news article or news organization. And it hasn’t been the PACE trial on its own. If that were the case, the fact that it has been refuted convincingly would have ended the whole matter. The real obstacle is the paradigm that has dominated this domain of medicine and science for the last three decades–the paradigm that incorporates the deconditioning-and-false-illness-beliefs hypothesis and the accompanying GET/CBT treatment strategy. PACE was just its most obvious and prominent manifestation.

In the late 1980s, a committed commando of mental health professionals launched a successful campaign to impose this paradigm on research and health care policy involving what they called CFS. Over the years, these experts have gaslighted patients with misinformation while touting their own subpar work—much of which actually undermines rather than supports their claims of treatment effectiveness. Patients and others who have rejected this prevailing dogma have been dismissed by this group and its enablers as hysterical and anti-science zealots.

As I’ve suggested before, these biopsychosocial ideological brigades are this saga’s counterparts to President Trump and his immediate circle—they all remain in public denial about reality, whatever they actually believe privately. (I assume Professor Sir Simon Wessely, who prides himself on his clinical trial bonafides, recognizes that it is not acceptable for studies to include participants who can be “recovered” at baseline on key measures.)

In this context, top journal editors are performing the critical role of enablers, as have Republican senators like Mitch McConnell and Lindsey Graham in the US political realm. Like McConnell and Graham, these journal editors are smart, and they must or at least should know better. For whatever reason or collection of reasons, they cannot bring themselves to acknowledge that in this domain of science they have published what can only be called crap—and potentially harmful crap at that.

The steadfast refusal of editors at leading journals to protect the literature from egregious methodological and ethical violations is as disturbing to me now as it was when I started this project–even if it is no longer surprising. I guess a powerful paradigm can compel even very intelligent people to do stupid things.

By David Tuller, DrPH

News organizations continue to misrepresent ME (and its various iterations) in their coverage of what has come to be called long-Covid. A current UK example is Sunday’s Observer article by writer Eleanor Morgan, who is experiencing prolonged symptoms since falling ill last spring. (It’s on The Guardian site; the two organizations are linked in some way.) Here’s Morgan’s bio on the website for the literary journal Granta, to which she has also contributed: “Eleanor Morgan is a writer based in London. Her latest book, Hormonal: A Conversation About Women’s Bodies, Mental Health and Why We Need to Be Heard (Virago) is out now. She is also training as a psychologist.”

Much of Morgan’s Observer article is a well-written, sympathetic and informative account of how she and various others are coping with their health challenges and the accompanying emotional roller-coaster. Then the article tackles the possible relationship between long-Covid and what it refers to as chronic fatigue syndrome. That’s when it takes a wrong turn. Here’s the relevant passage:

CFS is often diagnosed when fatigue and other prolonged symptoms cannot be medically explained, but a “trigger” illness or event is commonly identified. The complex nature of CFS means that improved medical testing is only part of the picture for providing better help for those living with it. Exploring the emotional component is integral, because CFS is often informed by a person’s underlying mental health and past experiences. Fatigue is compounded by catastrophic thinking. Patience, empathy and validation, then, are key to any successful care pathway, particularly in light of the well-established link between CFS and those who have experienced childhood trauma. The precise underpinnings of this link are not fully understood, but it’s clear.

Ok, then. Where to start? The “well-established” and “clear” link between CFS and a history of childhood trauma exists mainly in the imaginations of those who perpetuate this belief. The same is true for the argument that the illness is “informed” by someone’s mental health status. The purported evidence for such claims falls apart under scrutiny. People with a history of childhood trauma are more likely in general to have poorer health outcomes. This has nothing specific to do with CFS.

The same is true of the notion that the illness is “compounded by catastrophic thinking.” This hypothesis is promoted by the CBT/GET ideological brigades, who find in their studies that patients reporting worse symptoms are also those categorized as “catastrophizing” based on their responses to a set of questions. Yet the questions that supposedly measure “catastrophizing” are themselves suspect because they appear to presume the respondents do not suffer from a serious organic illness and that therefore expressions of concern about symptoms are inherently exaggerations qualifying as “catastrophizing.”

In any event, the trouble with this apparent association between “catastrophizing” and worse outcomes is that the causal relationship is just as or more likely to run the other way—those who have worse physical symptoms are more likely to accurately predict that they will continue to have worse physical symptoms. In other words, they have correctly interpreted reality, not “compounded” their suffering with irrational “catastrophic thinking.”

When such misrepresentations appear in widely circulated articles, it is easy to blame the writers—and of course anyone putting out health information to the public should be held to appropriate standards. But often reporters and journalists are themselves subject to the misinformation disseminated by supposedly reputable sources—and might not realize they are getting suckered.

I do not consider the Science Media Centre, Professor Sir Simon Wessely, the PACE authors, and their cabal of like-minded colleagues to be reputable sources. They all have a long history of perpetuating untruths in this domain of science. Unfortunately, journalists not steeped in this saga will often end up relying on what Irish psychologist Brian Hughes has called “eminence-based medicine”—as seems to have happened here.

Anyone writing on the issue of ME/CFS, including Morgan, should certainly take it upon themselves to review the new NICE draft of clinical guidelines for the illness. These recommendations repudiate the standard but bogus arguments still being advanced by the ideological brigadiers, which have now been replicated in the CFS section of this article.

**********

ME Association responds to The Observer

The Observer article has occasioned much comment among the ME twitterati and in online discussion groups. Charles Shepherd, medical adviser to the ME Association, has sent the following letter to the news organization:

Dear Editors

Re: https://www.theguardian.com/…/eleanor-morgan-is-still…

The article on Long COVID by Eleanor Morgan contains factual inaccuracies about factors that (a) predispose a person to developing ME/CFS and (b) perpetuate ME/CFS.

I refer, in particular, to the following paragraph:

“Exploring the emotional component is integral, because CFS is often informed by a person’s underlying mental health and past experiences. Fatigue is compounded by catastrophic thinking. Patience, empathy and validation, then, are key to any successful care pathway, particularly in light of the well-established link between CFS and those who have experienced childhood trauma. The precise underpinnings of this link are not fully understood, but it’s clear.”

There is no solid research evidence to substantiate claims that:

1 CFS is often informed by a person’s underlying mental health and past experiences

2 Fatigue is compounded by catastrophic thinking

3 There is a well-established link between CFS and those who have experienced childhood trauma

All three inaccuracies require a factual correction as soon as possible.

I would suggest that the author also has a look at the new NICE guideline on ME/CFS:https://www.nice.org.uk/…/GID…/documents/draft-guideline

And whilst appreciating that Dr Tomlinson is expressing an opinion, there is again no evidence to show that the development of either ME/CFS or Long COVID are ‘rooted in trauma’.

As a doctor with personal experience of developing a severe post viral fatigue syndrome following a chickenpox encephalitis infection I had a very happy childhood with no history of childhood trauma, or any other trauma.

Like everyone else with ME/CFS, and LongCOVID, I failed to recover from viral infection and do not want to be told that it was caused by having a traumatic childhood

Your sincerely

Dr Charles Shepherd Hon Medical Adviser, ME Association

Research reference relating to childhood adversity and ME/CFS: https://meassociation.org.uk/…/MEA-Summary-Review…

TWiV 685: Pandemicky

The TWiVers analyze efficacy of the AstraZeneca/Oxford adenovirus vectored vaccine, SARS-CoV-2 did not infect miners who became ill 8 years ago after cleaning bat guano from a cave in Yunnan Province, and induction of antigen-specific germinal center responses and production of neutralizing antibody by SARS-CoV-2 mRNA vaccine but not purified protein.

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Daniel Griffin provides a clinical report on COVID-19, and Shane Crotty explains a study of antibodies, B cells and T cells in patients which suggests that immunological memory to SARS-CoV-2 might be long-lived.

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By David Tuller, DrPH

On November 12, I received my latest letter from BMJ’s so-called research integrity office about the pile of potential research misconduct otherwise known as the pediatric study of cognitive behavior therapy and music therapy as a treatment for chronic fatigue after acute EBV. This study was published in April by BMJ Paediatrics Open and immediately came under sharp and justified criticism–including from me.

[continue reading…]

By David Tuller, DrPH

I have written multiple posts this year about a Norwegian study of cognitive behavior therapy plus music therapy as a treatment for chronic fatigue after acute EBV infection (aka mononucleosis and glandular fever). The study, published in April by BMJ Paediatrics Open, was rife with methodological and ethical flaws. It should not have been accepted in the first place.

[continue reading…]

By David Tuller, DrPH

As Trump’s legal team continues to spout nonsense rather than acknowledge that the orange balloon lost the election, core members of the UK’s biopsychosocial ideological brigades are also engaged in embarrassing denialism. Last week, a draft of new ME/CFS clinical guidelines issued by a key British health agency advised against graded exercise therapy and cognitive behavior therapy—the two interventions long recommended as paths to recovery. Several of the experts most associated with these rejected approaches promptly launched an unconvincing counter-attack, courtesy of the UK’s Science Media Centre–a purportedly neutral purveyer of scientific information to journalists and the public.

[continue reading…]

CoV2-cigarette

Cigarette smoking appears to be associated with more severe COVID-19, but the underlying mechanisms have not been deciphered. The results of infection of airway cells in culture with SARS-CoV-2 provide some insight.

Smoking is the most important cause of chronic lung disease, which in turn is a risk factor for severe COVID-19. Some studies have identified cigarette smoking as a risk factor for severe COVID-19, and chronic smoke exposure appears to trigger the expansion of cell types in the respiratory tract that produce ACE2, the receptor for SARS-CoV-2. But there have been no direct studies to determine how cigarette smoke affects SARS-CoV-2 infection of the airway epithelium.

To address this question, air-liquid interface cultures of respiratory epithelium from non-smokers were studied. Such cultures are initiated by plating cells taken from the human respiratory tract on a permeable membrane. When medium is removed from the top of the cell layer, it develops into a mucociliary pseudostratified epithelium, similar to the respiratory epithelium. When treated with cigarette smoke and then infected with SARS-CoV-2, these cells in culture produced 2-3 times more viral RNA compared with unexposed cells. Furthermore, the number of infected cells increased in cigarette smoke-treated cultures.

To understand the mechanism by which treatment with cigarette smoke leads to increased viral replication, single-cell RNA sequencing was done to determine the alterations of mRNAs caused by virus infection. This analysis identified a set of genes whose transcription was induced by virus infection of untreated cells, but down-regulated in cigarette smoke-treated cells. These genes encode interferon induced proteins, suggesting that exposure to cigarette smoke impairs an effective innate immune response to infection. In support of this hypothesis, addition of interferon to cultures after treatment with cigarette smoke, but before infection, blocked the production of infectious virus.

These observations do provide some insight into the effect of cigarette smoke on infection of airway epithelial cells with SARS-CoV-2. The finding that viral RNA increased in smoke-treated cells should be extended to determine if the amounts of infectious virus also increases. Blocking virus production with interferon does not illuminate the effect of smoke treatment because this cytokine also blocks infection in untreated cells. It would be more informative to specifically restore the expression of the interferon-induced genes that are reduced by smoke treatment.

Would a 2-3 fold increase in virus production, and a similar increase in the number of infected cells after smoke treatment of these airway cultures, explain why smokers might be a risk for serious COVID-19? A reduced innate immune response might allow substantial viral reproduction in the tract, which could in turn stimulate the over-exuberant immune responses that drive serious COVID-19. However an increase in viral yields alone seems too simplistic to explain the association of serious disease with smoking. An intriguing hint is the effect of cigarette smoke airway basal stem cells, which are important for the repair of damaged airways. Smoke not only increases the number of these cells but also leads to their death. Such an effect could worsen tissue damage in the infected respiratory tract, leading to more severe disease.

On this episode of TWiV, mRNA vaccines from Moderna and Pfizer show over 90% efficacy, prothrombotic auto-antibodies in serum of COVID-19 patients, and the whereabouts of SARS-CoV-2 in the human body.

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From Expedition 64 of International Space Station, Flight Engineer Kate Rubins joins TWiV to discuss experiments that she is working on, including cell cultures, genome sequencing, and plant growth.

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