Opinion How methodological pitfalls have created widespread misunderstanding about long COVID, 2023, Høeg, Ladhani, Prasad

[SNT Gatchaman]

How methodological pitfalls have created widespread misunderstanding about long COVID
Tracy Beth Høeg; Shamez Ladhani; Vinay Prasad

Key Messages

The existing epidemiological research on long COVID has suffered from overly broad case definitions and a striking absence of control groups, which have led to distortion of risk.

The unintended consequences of this may include, but are not limited to, increased societal anxiety and healthcare spending, a failure to diagnose other treatable conditions misdiagnosed as long COVID and diversion of funds and attention from those who truly suffer from chronic conditions secondary to COVID-19.

Future research should include properly matched control groups, sufficient follow-up time after infection and internationallyestablished diagnostic or inclusion and exclusion criteria.

Link | PDF (BMJ Evidence-Based Medicine)

 

[SNT Gatchaman]

Authored by notorious (on social media) Covid minimisers. ME/CFS does not appear to have been mentioned.

 

[SNT Gatchaman]

Hard to know where to start with this. Of course they quote all our previously debunked and superseded papers, starting predictably enough with Matta et al.

They end by asking for eg —

more stringent PASC criteria, which should include continuous symptoms after confirmed SARS-CoV-2 infection and take into consideration baseline characteristics, including physical and mental health, which may contribute to an individual’s postCOVID experience.

Meanwhile the patients pretty much universally describe initial recovery from acute infection, going back to life and then developing symptoms of LC, typically at 6-12 weeks.

Many had no prior physical or mental health problems. Some infected people don't test positive for multiple reasons. And we now know that a significant proportion of people have asymptomatic infection, demonstrable later with immune evaluation.

 

[SNT Gatchaman]

a well designed Swiss study used antibody seroconversion during the study period to confirm SARS-CoV-2 infection in children. In randomly assigned school classes at the end of 2020, they found essentially the same prevalence of lasting symptoms among 12-16 year olds who had been infected compared with those who had not been. Specifically they found 9% of antibody-positive children had at least one symptom after 4 weeks compared with 10% of those without antibodies.

Leaving aside the potential issues with using seroconversion to classify prior Covid infection (see here).

Odd that this paper doesn't also reference one of the author's (SL) prior studies: Long COVID in Children and Youth After Infection or Reinfection with the Omicron Variant: A Prospective Observational Study (2023)

Presumably this must have been a well designed study. It found —

12-16% infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first-positive and reinfection

 

[TiredSam]

Saw this on my Sky News app and smelt a rat immediately ...

https://news.sky.com/story/long-covid-risks-are-distorted-by-flawed-research-study-finds-12969777

Although there is a little balance at the end

However, Dr Adam Jacobs, senior director of biostatistical science at Premier Research, said although the paper "makes some sensible points" it goes on "to draw some odd conclusions".

 

[rvallee]

Link | PDF (BMJ Evidence-Based Medicine)

This is in the Evidence-based Medicine journal of the British Medical Association. Good grief, medicine firmly is in the post-truth era. These 3 ideologues have basically been wrong about the whole thing and here they are, not only writing a "akshually, everyone else is wrong" article, but getting it published in a publication called Evidence-Based Medicine owned by one of the most reputable medical associations in the world.

There is a huge overlap between these quacks and the antivaccine crowd. Where of course they are currently being praised for repeating the same stuff they've been saying from the start. Either they don't notice, or they don't care. But even worse is that just like the Wakefield MMR paper got the big nod and praise from The Lancet, this is getting the assent of the British Medical Association. And of course Ladhani, despite being a LC denier from the start, is part of the LC research study on children in the UK with Esther Crawley.

The regression of human medicine, especially its culture and sociopolitical aspects, right on the cusp of AI medicine is really something to behold. Instead of admitting they got things wrong, they just keep escalating commitment to old lies. Lies that harm, injure and kill, but somehow are comforting to them. It's so revealing about human nature, about why atrocities are so common.

Here is a pretty good thread on how closely aligned the authors of this drivel are to the antivaccine movement, how they echo it when convenient for them, and of course how they are echoed back. They are reactionaries, in the most typical sense, and are simply guided by their self-interest. Something that should not even exist in medicine, has become the dominant paradigm, to the point where the germ theory of disease has been turned upside down and now infections are good, in fact the more you have the better they are. Humans truly are our own worst enemy.

I think serious questions need to be asked if it's appropriate for the UKs clinical lead for covid in children to be coauthoring multiple papers with Hoeg and Prasad, both have an awful track record of making misleading claims, particularly in regards to vaccines

Hoeg was one of the key people responsible for massively exaggerating the risk of vax myocarditis in children, papers publication was headlines by Turner of the Telegraph Awful disinformation that damaged parents confidence and emboldened antivaxxers

Hoeg and Prasad were involved in Urgency of Normal, an effort in the US to claim covid in schools and children was negligible and could be ignored Huge issues with what UoN produced

The fact they defended DeSantis' AFLD linked SG Ladapo's anti-vax paper should have all Ladhanis UKHSA questioning his choices, however I'm going to bet they just look the other way

As Ladhani’s minimising claims have become harder to maintain as evidence emerges of the harms that can occur to children he has become increasingly reliant on quoting Hoeg For instance discounting covid causing diabetes BTW we have seen a surge

It's also worth that Ladhani is the UKs Clinical Lead, advised SAGE and JCVI, sat on the WHOs technical advisory group on covid in children (world wide group and euro group) and is the most cited paedatrician on covid in the world

So by working with Hoeg and Prasad, consider the veneer of respectability someone in his position confers to the pair, in particular Hoeg who has a track record of misrepresenting her credentials and expertise

Consider Hoegs membership of the Norfolk Group with its dark money Links and connections to the GOP, which has now become DeSantis covid committee These ppl aren't neutral players pursuing science, they're deeply political

 

[Dolphin]

Science Media Centre commentary from, inter alia, Paul Garner and Danny Altmann


expert reaction to an analysis of the body of research on long COVID suggesting potential methodological flaws
https://www.sciencemediacentre.org/expert-reaction-to-an-analysis-of-the-body-of-research-on-long-covid-suggesting-potential-methodological-flaws/

 

[SNT Gatchaman]

Meanwhile the patients pretty much universally describe initial recovery from acute infection, going back to life and then developing symptoms of LC, typically at 6-12 weeks.

Good to see this point (among others) being expanded on in the SMC expert reaction.

The authors of the new study seem to want to require that definitions of long COVID must require symptoms to be ‘persistent or continuous’. They say that three of the four definitions that they quote, all but the CDC definition, require this. I think that’s an odd reading of those definitions. The WHO definition does not mention anything about the symptoms being persistent or continuous. The definition from NICE and other groups says that the symptoms “can fluctuate and change over time”, and the Delphi definition says that symptoms “may fluctuate or relapse over time” (and, incidentally, this definition is not for children and young people, despite what Table 1 in the new paper says). None of this sounds like ‘persistent or continuous’ symptoms to me. And it’s hardly a new thing that symptoms caused by infections might not arise for some time after the initial infections. An extreme case is shingles, which is caused by the virus that causes chickenpox. That can stay inactive in the body for years or decades, before emerging again in the form of shingles.

 

[Sean]

From Dr Adam Jacobs' response at the Science Media Centre:

However, if some of the even moderately pessimistic, let alone the most pessimistic, studies are correct, then long COVID could represent a public health catastrophe the likes of which has not been seen in modern times.

 

[Dolphin]

Has the risk of getting long covid been overestimated?

Long covid, the experience of lingering symptoms after a covid-19 infection, remains a poorly understood condition, and researchers disagree on how common it is

By Clare Wilson

27 September 2023

https://www.newscientist.com/article/2393962-has-the-risk-of-getting-long-covid-been-overestimated/

 

[SNT Gatchaman]

and researchers disagree on how common it is

-> "and some researchers deny how common it is"

In some ways, the exact number of people with long covid may not make much difference to those who have the condition. What they really want is to get better – and unfortunately, this doesn’t tell us anything about how best to achieve that.

For sure though denying its prevalence will prevent that research from being funded.

 

[ME/CFS Skeptic]

Hard to know where to start with this. Of course they quote all our previously debunked and superseded papers, starting predictably enough with Matta et al.

Yes that already indicates that this paper isn't about increasing quality standards. The paper by Matta et al. is probably more flawed than whatever they are criticising here.

That's quite unfortunate because I do have been disappointed in how poorly Long Covid has been studied by the epidemiological community. The case definitions are obviously too broad and most studies did no attempt to include a control group or avoid selection bias. I suspect that 90% or so of the literature is useless in this regard. As far as I'm aware there still haven't been a decent study that tracked ME/CFS prevalence following COVID infection.

But instead of calling for improved methodology, this paper seems to argue that Long Covid probably does not exist at all. They write:

"When limiting studies to those with acceptable PASC definitions and appropriate controls, we find little to no difference in the prevalence of reported persistent symptoms in children by 4 weeks or in adults younger than 50 years by 12 weeks postinfection compared with controls."
​

The study in adults they are referring to seems to be the ONS data which is quite misleading because that report itself says that Long Covid rates at 12 weeks range from from 3.0% to 11.7% depending on the definition used. This paper seems to have used only data on 'Prevalence of any symptom at a point in time after infection' - which is far from a good case definition for Long Covid.
Technical article: Updated estimates of the prevalence of post-acute symptoms among people with coronavirus (COVID-19) in the UK - Office for National Statistics (ons.gov.uk)

 

[ME/CFS Skeptic]

Also strange that they don't cite the Lifelines study (Ballering et al. 2022) which found:

In 12·7% of patients, these symptoms could be attributed to COVID-19, as 381 (21·4%) of 1782 COVID-19-positive participants versus 361 (8·7%) of 4130 COVID-19-negative controls had at least one of these core symptoms substantially increased to at least moderate severity at 90–150 days after COVID-19 diagnosis or matched timepoint.
​

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01214-4/fulltext

 

[ME/CFS Skeptic]

The authors also write about another study in 12-16 year olds:

Specifically they found 9% of antibody-positive children had at least one symptom after 4 weeks compared with 10% of those without antibodies.25
​

But reference 25 points to

Antonelli M, Pujol JC, Spector TD, et al. Risk of long COVID associated with Delta versus Omicron variants of SARS-Cov-2. Lancet 2022;399:2263–4. ​

Which seems to describe another study. Anyone knows which study in 12-16 years old they might mean?

 

[ME/CFS Skeptic]

It seems that the last author published 78 papers in 2022, or about 1 every 5 days. Does not give much confidence that he has methodology at heart when writing articles like this one.
Papers — Vinay Prasad MD, MPH (vinayakkprasad.com)

 

[SNT Gatchaman]

But reference 25 points to [...] Which seems to describe another study. Anyone knows which study in 12-16 years old they might mean?

Jeremy Rossman pointed out the reference problems in the SMC commentary.

“And finally (and I mention this really only to avoid anyone else having to do what I did and dig around to find what’s really where), the reference numbers given in the section headed “The most well-designed studies provide reassuring estimates” are wrong. The ONS study listed in the text as having reference 21 is really reference 23. The one listed in the text as reference 23 is really 24, and the one listed as reference 24 is really 25. And, in the next paragraph, the Swiss study, said to have reference 25 is in fact reference 22, and that reference is to an overall website for a linked series of projects in Switzerland, where one has to dig out the relevant paper from a list of over 60 publications. The specific paper is actually at https://jamanetwork.com/journals/jama/fullarticle/2782164.”

 

[SNT Gatchaman]

https://bsky.app/profile/realnosferatu.bsky.social/post/3kblau7uyog2p

And in good news…. Vinay Prasad has been removed as Keynote Speaker for the American College of Clinical Pharmacy conference. Accountability works. Never stop raising your voice.

 

[rvallee]

That he was invited at all as a speaker is problematic in itself, but as keynote? Good grief.

 

[SNT Gatchaman]

Correspondence on “How methodological pitfalls have created widespread misunderstanding about long COVID” by Høeg et al (Thomas R Fanshawe, Nuffield Department of Primary Care Health Sciences, University of Oxford) —

the authors also make some statements that are factually incorrect, such as claiming that studies might use “serology to confirm prior infection, which can be done at any time”, they later contradict this themselves, in the section 'Sampling bias'. Their discussion of the symptom outcome definition neglects issues such as multiplicity of symptoms and symptom severity, appearing to prefer a definition based on individual symptoms.

I feel that the authors' claim that “the most well-designed studies provide reassuring estimates” also needs to be challenged. The conclusions drawn in this section are based on only two studies and undermine the strength of the evidence from large-scale systematic reviews and cohort studies of post-COVID sequelae. There may be some limitations in the evidence base, but that is not a reason to summarily ignore it. Might 'avoid confirmation bias' be added to their list of recommended criteria for epidemiological research?

Among the two studies cited is the Office for National Statistics (ONS) survey, whose control group does not meet the criteria for adequate matching that the authors have themselves stipulated. Further, the figure of 2.9% prevalence, which by implication the authors consider to be low, is a population-level prevalence, which is therefore an average across both infected and uninfected individuals and would be expected to be lower than the risk of long COVID among those infected with SARS-CoV-2, as estimated in many cohort studies. Even the most stringent case definition in the ONS report (which requires ongoing symptoms at least 2 years after initial infection) yields an estimate of 762 000 individuals in the UK with ongoing symptoms, this constitutes a substantial ongoing healthcare burden. Population-level estimates from the USA are somewhat higher.

Given the magnitude of these figures, it is hard to see how the authors could subjectively conclude them to be ‘reassuring’. They have not provided any evidence for other claims in the paper, such as that limitations in the research base have led to ‘increased societal anxiety’. They attribute this partly to media reporting; this is also a curious claim, given public health messaging frequently focuses on the prevention of mortality in the acute phase rather than the prevention of long-term disability.

Author reply: Reliance on the highest-quality studies of Long Covid is appropriate and not evidence of bias —

historical studies that employed a change in seropositivity status to distinguish infected cases from controls are expected to be more accurate than those relying on antigen or PCR test positivity alone. Studies using serology status minimise the bias created by misclassifying cases with mild or no symptoms as 'uninfected controls.' The studies cited in our paper that used serology were well-designed. They did not find a significant difference in prevalence of Long Covid between cases and controls, highlighting the very low risk of persistent symptoms after infection.

Notably, one of the strongest risk factors for developing Long Covid was pre-existing psychological diagnoses, indicating—even in this study with reassuringly low incidence—that the number of the Long Covid diagnoses may have been overestimated due to misclassification.

The review Dr. Fanshawe cites as evidence Long Covid is ‘multifactorial’ and ‘debilitating’ is unreliable for multiple reasons. First, it indicates 10%–30% of people who are not hospitalised with COVID-19 suffer from Long Covid. We can see this statistic is unrealistic prima facie now that most of the population has been infected at least once and 10%–30% of people do not suffer from Long Covid.

 

[SNT Gatchaman]

On the subject of serology, see this recent talk by Lisa Chakrabarti from the Institut Pasteur on divergent T cell responses. She reviews studies that show excessive or insufficient immune adaptive responses and proceeds to discuss their study into working out why.

"It's important to point out that among the 51 Long Covid patients studied, 23 were seronegative. They had no antibody to the spike. We chose to study these patients because they represented up to one third of the patients in Dominique Salmon's cohort and also because they have not frequently been included in physiopathological cohort studies. Because often their infection is not documented."