virology blog

Trial By Error: In Guardian Column, Professor Pariante Parrots Standard Biopsychosocial Nonsense

1 May 2021 by David Tuller 10 Comments

By David Tuller, DrPH

On Tuesday (four days ago), The Guardian published an opinion piece from Professor Carmine Pariante titled “Long Covid is very far from ‘all in the mind’–but psychology can still help us to treat it.” The article is the latest from a member of the biopsychosocial ideological brigades to demonstrate what has long been apparent—those who proclaim that others are falling into an unhelpful mind-body dichotomy are using this argument to deflect attention from the failings of research into their favored interventions. Professor Pariante is a psychiatrist based at King’s College London, the home of Professor Trudie Chalder, Professor Sir Simon Wessely, and other leading lights of the biopsychosocial firmament, so he is likely steeped constantly in a brew of self-reaffirming but unwarranted assertions.

Professor Pariante’s piece has been published in the wake of two articles by Guardian columnist George Monbiot. The first column, in January, expressed alarm about the epidemic of Long COVID cases. The second column, published last month, took a sledgehammer to Professor Michael Sharpe’s creative accusation that Monbiot was causing Long COVID just by having written about it in the first place. It was clear from Monbiot’s second column and a detailed Twitter thread that he’d quickly learned a whole lot about the PACE trial disaster.

Professor Pariante’s new piece appears to be part of an ongoing campaign seeking to prevent the unraveling of the biopsychosocial paradigm for ME/CFS–and by extension for Long COVID. As is usual for this group, Professor Pariante reassures us that patients’ symptoms are “real” and should be taken seriously. But he undermines that message by suggesting that patients with ME/CFS—or CFS/ME, as he calls it—reject psychologically oriented interventions because they don’t fully appreciate the relationship between mental and physical health.

Professor Pariante should know better than to parrot such silliness. Perhaps he needs to spend more time listening to patients’ concerns and less to the theoretical blatherings of his fellow campaigners. No one seriously disputes that emotional and psychological states can influence how we experience symptoms and disease. That is a straw-person argument. At issue is the quality of the research behind the claims being made. As has been documented over and over, the research on cognitive behavior therapy and its companion, graded exercise therapy, for ME/CFS is fraught with disqualifying flaws and does not prove what it claims to prove. Patients frown on these interventions because the studies are crap—not because of prejudice against psychiatry or psychological interventions. Rejecting CBT as a treatment for ME/CFS cannot reasonably be construed as a denigration of people with mental illness.

It is long past time for “experts” like Professor Pariante to drop these specious claims about patients’ motivations and face reality: The PACE trial seems to meet common definitions of research misconduct, and the overall CBT/GET literature is equally unconvincing. In the course of developing the draft of its new ME/CFS guidelines, the National Institute for Health and Care Excellence (NICE) conducted a thorough review and found most of the evidence for the current interventions to be of “very low” quality and the rest of “low” quality.

Presumably Professor Pariante and his colleagues don’t agree, but that’s too bad. Whatever they think, this NICE evidence review is the most authoritative recent assessment. The draft NICE released in November rejected the perspective on ME/CFS treatments that Professor Pariante has just espoused in The Guardian. Hopefully, the final version of the NICE guidelines will adhere closely to that draft, despite ferocious push-back from the biopsychosocialists.

Professor Pariante’s comparison of the use of CBT in the field of cancer to its use in ME/CFS is one frequently invoked by like-minded professionals. Cancer patients are obviously not told they can be cured with CBT, so the comparison is ridiculous, irrational and insulting. Does Professor Pariante think that cancer patients should be satisfied with CBT and that those who want pharmaceutical treatments are too wedded to a bifurcated view of mind and body? What about patients with Crohn’s or Parkinson’s? ME/CFS has nothing to do with Descartes or Cartesian dualism, no matter how often Professor Sharpe, Professor Pariante, and their colleagues opine that these patients are suffering from philosophical confusion over mind-body matters.

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In the meantime, The Guardian this week posted a succinct and spot-on response to Professor Pariante from Dom Salisbury, an ME/CFS patient in Lancashire. Here’s a brief description from his website: “Prior to becoming too ill to maintain a job, I worked in scientific research in the fields of atmospheric and ocean physics. I obtained my PhD from the University of Leeds in 2014, with a thesis investigating the role of ocean wave-breaking and whitecaps on air-sea exchange.”

I’d be hard-pressed to comment authoritatively on Dr Salisbury’s discoveries about wave-breaking and whitecaps and air-sea exchange. But I agree with every point in his letter to The Guardian. I’m reposting it here, with his permission:

In reviewing the possible role of psychology in treating long Covid, Dr Carmine Pariante misrepresents why many ME/chronic fatigue syndrome patients remain sceptical about psychological interventions such as cognitive behavioural therapy (CBT). It is not because we deny the important overlap between mental and physical illness, but rather because these interventions are offered as treatments based on poor-quality evidence of short-term marginal improvements in some patients.

No cancer patient is offered psychotherapeutic interventions as treatment; rather, these therapies play a supportive role for patients who require them. In contrast, CBT has been recommended as a first-line treatment for ME/CFS for more than a decade. Indeed, the dominance of the biopsychosocial model of ME/CFS – with its emphasis on the roles of thoughts and behaviour, rather than pathology – is one of the reasons why long Covid patients are now facing such limited options in clinics.

Dr Dominic Salisbury
Lytham St Annes, Lancashire

Defective genomes modulate respiratory syncytial virus pathogenesis

29 April 2021 by Vincent Racaniello 2 Comments

During viral replication, defective genomes may arise that lack essential sequences. These so-called defective genomes cannot replicate unless they are in the same cell as a helper virus. Defective genomes play a role in modulating pathogenesis of respiratory syncytial virus in humans.

Copy-back defective viral genomes (cbDVGs) of RSV arise when the viral RNA polymerase halts and then turns around and begins copying the nascent strand (illustrated below – image credit). Because the cbDVGs have strands of both (+) and (-) polarity it is possible to design primers to amplify them by RT-PCR.

It has been suspected that defective viral genomes might modulate viral pathogenesis because they are efficient inducers of interferon. In a study of 122 hospitalized pediatric patients with RSV infection, the presence of cbDVGs was associated with higher viral loads and longer hospitalizations. Furthermore, patients harboring cbDVGs had higher expression of pro-inflammatory cytokine genes.

Unexpectedly, non-hospitalized patients with confirmed RSV infection also had high levels of cbDVGs and high viral loads. Analysis of the kinetics of cbDVG production revealed that when cbDVGs arise early in infection, less severe symptoms present. In contrast, when cbDVGs arise later in infection, higher viral loads and more severe disease occur. The latter patients also produce higher levels of pro-inflammatory cytokines which likely cause immunopathogenesis.

An interpretation of these findings is that when cbDVGs arise early in infection, they induce antiviral immune responses that limit viral replication and disease. When cbDVGs arise later, the virus has already reproduced to high levels, leading to more severe disease. The factors that regulate cbDVGs production are not known, but could involve sex, age, immune status, and the levels of the defective genomes in the virus inoculum.

These results are of interest because it has not been possible to predict which RSV infected patients will develop severe disease. It might be possible to use levels of cbDVGs to forecast clinical outcome.

When defective viral particles were discovered many years ago, Alice Huang proposed that they might modulate viral pathogenesis. It was not until the 1990s that the technology became available to test this hypothesis. The results with RSV suggest that whether cbDVGs are beneficial or detrimental depends on when they arise in infection.

Trial By Error: Professor David’s Third Mis-Citation of Seminal Study of “Medically Unexplained Symptoms”

26 April 2021 by David Tuller 14 Comments

By David Tuller, DrPH

*April is crowdfunding month at Berkeley. I conduct this project as a senior fellow in public health and journalism at the university’s Center for Global Public Health. If you would like to support the project with a donation to Berkeley (tax-deductible for US taxpayers), here’s the place: https://crowdfund.berkeley.edu/project/25504

I have recently blogged about the multiple mis-citations of a seminal study involving so-called “medically unexplained symptoms” (MUS). The 2010 study, Bermingham et al, found that the amount spent by the National Health Service on working-age people who were assessed as “somatising” accounted for around 10% of what was spent on that population. Since the study was published more than a decade ago, experts in MUS have routinely misrepresented it by asserting that these costs accounted for 10% of total NHS expenditures—in effect more than tripling their apparent financial impact.

Trial By Errors: Why Have Experts in MUS Spent Ten Years Mis-Citing a Study about Costs to the NHS?

23 April 2021 by David Tuller 6 Comments

By David Tuller, DrPH

What does it mean that the top investigators in a field of research have collectively and consistently misrepresented a seminal figure in their purported domain of expertise? I’m talking about all those who present themselves as authorities on the topic of so-called “medically unexplained symptoms” (MUS) but have found it difficult to accurately cite a study that examined the purported costs of these conditions to the National Health Service. (This phenomenon was initially pointed out to me by an observant sleuth; I first wrote about it here.)

The study in question, Bermingham et al, is called “The cost of somatisation among the working-age population in England for the year 2008-2009.” It was published in 2010 in the journal Mental Health in Family Medicine. As one of its core findings, it estimated something very specific: NHS costs for patients of working age identified as “somatising” to even a minor extent accounted for around 10% of the total costs for that demographic category. In paper after paper, “experts” in MUS have translated that straightforward data point this way: Patients with MUS accounted for 10% of total NHS costs. The effect of that error is to more than triple the apparent impact of MUS on the NHS budget.

SARS-CoV-2 variants arise during individual infections

22 April 2021 by Vincent Racaniello 3 Comments

Early in the COVID-19 pandemic, SARS-CoV-2 genome variation appeared to be low, with an average of 10 base differences in the 30,000 base genome between any two isolates. Late in 2020, as many more people were infected, variants were isolated that had more changes than previously seen. A study of variation at the genome level indicates that diversity in a single host has been underestimated.

SARS-CoV-2 variants certainly arise in each infected individual, and these may be subjected to selection pressures such as those imposed by antibodies binding to spike protein. Commonly used sequencing technologies do not permit detection of virus variants within single samples. To address this limitation, a high-throughput sequencing method was developed for sequencing individual virus RNA genomes in patient samples. The results demonstrate that SARS-CoV-2 variants emerge in each host and are subject to immune selection pressure.

When this method was used to analyze a patient isolate of SARS-CoV-2 after four passages in Vero cells, in the regions encoding spike, ORF3, envelope, and M protein, 18 unique combinations of mutations were detected. Over half of the single genome sequences differed from the reference sequence. Many of the changes led to amino acid substitutions, suggesting selection pressure occurring during cell culture adaptation.

In-host diversity was then examined for 7 patients sampled between days 8 and 17 of illness onset. Only a few sequence haplotypes were detected, with no clear consensus among the amino acid changes. These relatively homogeneous sequences might have been a consequence of sampling early in infection when limited antibody pressure was present. Examination of the antibody response in longitudinal samples revealed an increasing and broadening antibody response to the spike.

A study of antibody responses and presence of mutations in individual genomes revealed a correlation between the emergence of antibodies to the N-terminal domain of spike protein, the emergence of amino acid changes in regions that bind these antibodies, and a delay in clearance of virus. These results are consistent with antibody pressure during infection leading to selection of SARS-CoV-2 spike variants (pictured).

SARS-CoV-2 variation in a single host had not been previously described, probably due to the inability of previous sequencing methods to distinguish variation from technical errors. It is also likely that high-quality data were acquired early in infection when viral titers are high yet antibody pressure is not yet present.

There are several take-home messages from these findings. They illustrate how diversity in a single host might give rise to antibody-resistant variants that could spread in a population if they have the appropriate fitness. In-host escape might be avoided by containing viral reproduction early in infection, either by prior immunity or by antiviral therapy, before selection by antibody takes place. This method should be applied to studying more COVID-19 patient samples to understand the extent of potential in-host SARS-CoV-2 variation.

Trial By Error: More on the Lightning Process and the Science Media Centre’s Collusion With UK Journalists

22 April 2021 by David Tuller 3 Comments

By David Tuller, DrPH

My story on the Lightning Process this week, published by Coda Story, was pretty long. Even so, it didn’t cover everything I would have liked to include. Here a bit more about the issue.

As we now know, the pediatric Lightning Process study conducted by Professor Esther Crawley, Bristol University’s methodologically and ethically challenged pediatrician, violated core concepts of scientific inquiry but was published anyway. BMJ whitewashed what appeared to be research misconduct by posting a 3,000-word correction/clarification rather than retracting the paper.

Trial By Error: Do the “Vast Majority” of Lightning Process Participants Achieve “Lasting Change”?

21 April 2021 by David Tuller 6 Comments

By David Tuller, DrPH

Coda Story is an excellent news organization focused on international stories related to the misuse of science and technology, among other topics. Today, it published a piece of mine about the training program called the Lightning Process. Sites devoted to the Lightning Process are full of tales of recovery from prolonged illness. I included one such account in my Coda article along with accounts from others who reported suffering severe relapses after the training. The article also points out that the scientific claims cannot withstand scrutiny.

Trial By Error: Northwestern Law Professor Steven Lubet Corresponds with McMaster U. About That WSJ Op-Ed

19 April 2021 by David Tuller 12 Comments

By David Tuller, DrPH

A recent Wall Street Journal opinion piece accused an apparently powerful “queer feminist wellness collective” of causing an international wave of mental illness, which is being expressed as reports of persistent disabling symptoms after an acute bout of COVID-19. The article was written by a psychiatry resident at Canada’s McMaster University in Canada. Given the arguments advanced by the resident, my friend and colleague decided to check in with the university’s psychiatry department.

Here’s his report.

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Can McMaster University Medical School Psychiatrists Be Trusted to Treat ME/CFS Patients?

By Steven Lubet

Trial By Error: Letter to Lancet Editor Demanding Independent Investigation of PACE (Reprise from 2018)

18 April 2021 by David Tuller 2 Comments

By David Tuller, DrPH

Trial By Error: My Letter to Professor Anthony David Asks Why MUS Experts Keep Misquoting a Major Study

17 April 2021 by David Tuller 10 Comments

By David Tuller, DrPH

Earlier this week, I wrote to the journal Psychological Medicine about a significant mistake in a paper on functional neurological disorders. The mistake involved a misquotation of Bermingham et al, a key 2010 analysis of the National Health Service costs associated with care for working-age people found to be “somatising.” One of Psychological Medicine‘s two editors-in-chief, Professor Robin Murray of King’s College London, responded promptly and indicated that he was checking with the authors about the matter.

I subsequently followed up with Professor Murray to point out that the senior author of the paper was also co-author of another paper that had been corrected for the same mistake in October, 2019. He again responded promptly and indicated that he would check on it.