Fighting Goliath: a response

Cross-posted from The Wry Observer's blog

I purchased a copy of Norman Fenton and Martin Neil’s book “Fighting Goliath” having enjoyed, and been educated by their blog “Where are the numbers”. As a mundane clinician I found the statistical analysis hard going; we long-in-the-tooth doctors never had a great deal of statistical training in our youth, or if we did I found it incomprehensible then, so much of the knowledge has been relegated to the trash bin in my brain from where only fragments can be recovered. Yet their argument is very convincing; it takes me back 40 years to when one of my friends from medical school, who like me became a rheumatologist, destroyed a number of clinical trials results on non-steroidal anti-inflammatory drugs by demonstrating how a large number of procedural errors invalidated them. These ranged from inadequate trial size through selection bias to the use of the wrong analytical process. Later on I walked out of a conference when the pharmacodynamics of a new drug were tested on 12 people; one subject had a prolonged excretion half-life but was excluded from the analysis as an outlier. I questioned how one could ignore nearly 9% of the sample, and did not get a satisfactory response.

Thus both the use of Bayesian analysis to debunk some of the vaccine trial results was interesting and convincing. But a more fundamental issue raised by Fenton and Neil was the how you should define someone who is vaccinated. To decide arbitrarily that someone was not vaccinated until 14 days after they had been always seemed to me to be bizarre, and the effect of this is, of course, to bias the numbers of subjects getting side-effects, or Covid type symptoms, in the vaccines’ favour. From a clinical viewpoint the 14 day rule is quite simply wrong. The serious consequences of SARS-CoV-2, or its vaccine, both of which seem to relate to the effect of the spike protein on the immune system, will occur within hours. So what is now needed to set records straight is a complete re-analysis of all the trial and observational data using the baseline for date of vaccination as the date it was actually given. Will such a re-evaluation happen? I doubt it. Even with all the growing evidence of side-effects, failure of principle (vaccines neither alter transmissibility nor susceptibility to severe disease) repeat programmes have been set up. I was a good boy; believing what I was told I was “done” three times. It didn’t stop me getting the virus and on the third jab I got symptoms of myocardial dysfunction, though I have no concrete evidence to prove that I had myocarditis as our local health service is not geared up to check. But I am not having any more boosters.

So the vaccine experience has not proved successful. The evidence that they work, or that they do not produce significant side-effects, is either non-existent or flawed due to selection bias. In the context of NHS spending one has to question whether the vaccination programme is value for money.

Fenton and Neil have questioned also the entire basis of the pandemic and raised the question of whether SARS-CoV-2 is really the organism of concern. They have suggested that many of the seriously ill were actually suffering from bacterial pneumonia. Here I think they are (largely) wrong. Yes, Haemophilus influenzae may be cultured but it’s a normal commensal organism so it would be surprising if it wasn’t. Going back to 1892 reveals that a similar suggestion was made then, after one researcher, Richard Pfeiffer, found evidence of a bacillus, but during the 1918 Spanish flu pandemic it was not present more often than it was – and of course the identification of viruses then did not exist. CT scans cannot easily distinguish between pneumonia, alveolar haemorrhage or a combination of the two, so using scans as a marker for infective pneumonia is clinically inappropriate. One needs to have lung biopsies to prove the cause of the shadows, but for all sorts of good reasons these were never done. Neither, as I have said previously, were there any reasonable post-mortem studies because pathologists were ordered not to conduct autopsies. But the suggestion made me think, not least because I have long maintained that the serious consequences seen and attributed to SARS-CoV-2, or Covid-19, are due to a cytokine storm. If this is provoked by the spike protein then vaccines that cause the body to generate spike protein can similarly provoke trouble, which is so far the best fit explanation for what we have seen. But, as I have repeatedly posted, cytokine storms can be provoked by all sorts of things – other infections, introduction of immunogenic proteins, genetic predisposition etc (I still have to hear of anyone pontificating on Covid who has read the definitive cytokine storm textbook by Cron and Behrens. Furthermore I have yet to see a scientifically valid rebuttal of the cytokine storm theory of causation).

The cytokine storm is a fairly acute phenomenon. The time scale of its development is rapid. The systemic effects parallel the lung damage. The more you look, the better it fits. But the more you look and think about it the more you begin to realise that severe sepsis is also a cytokine storm effect. The damage one sees developing, with thromboses, myocardial dysfunction, renal impairment etc the more you start to wonder whether every and all severe sepsis case, irrespective of the underlying causative organism, kills people not because of aggressive damage by rapidly proliferating bugs but by the overreaction of the body to their presence. So rather than talk about Covid-19 as a specific entity we should lump it together with all other causes of sepsis, and forget SARS-CoV-2 as a stand-out, standalone bug. If a myriad of infections produce the same common path end result, the actual organism itself is irrelevant.

That is not to say that one should not treat an infection if you can. I would be the last person to withhold antibiotics from someone with a widespread infection and, having seen the devastating effects of joint infections in arthritis patients, antibiotics would be the first thing I would use. But the systemic sequelae will not respond to antibiotics and require specific immunosuppression. We knew this before Covid; Cron and Behrens specified the use of corticosteroids and specific interleukin antagonists (tocilizumab for Il-6, anakinra for Il-1). I have treated sepsis in multiple sclerosis with large steroid doses (and appropriate antibiotics, of course). I started doing so in the early 2000s and the effects were dramatic. The rationale is unquestionable and the evidence substantial.

So while I would dispute Fenton and Neil’s superinfection theory, and cleave to the concept of the spike protein being the major precipitant of the hyperimmune response called Covid-19, it is not a unique response and occurs in lots of infections. Does it matter what exact bit of a bug sets it all off? Should we therefore drop the designation of Covid-19 altogether, and start to discuss the real syndrome of which it is but one manifestation? And rename that syndrome – think of a name that produces a neat acronym. I have come up with Triggered HyperImmune Sepsis Syndrome, or THISS. THISS might be the enduring legacy of “Fighting Goliath” but I invented it and claim my prize.