Scare follows scare.
We started with SARS-CoV-2, or Covid if you wish to be inaccurate and incomplete. Next up – Hantavirus on a small cruise ship. Lastly the recrudescence of Ebola.
What do all these have in common? Three things.
Firstly, they are all RNA viruses. This means that they are all prone to mutation. SARS-CoV-2 has been through several identified iterations and is almost certainly derived from an existing and not very toxic strain through gain-of-function research; the recent Hantavirus outbreak (if it can be called that, as it is rather small) is due to the Andean strain, a mutant version of the original Korean version and the recent Ebola epidemic is likewise due to a variant.
One might suppose, therefore, that a vaccine against one strain of each virus might not work against another. So vaccination might not be appropriate, or necessary.
The next thing they have in common is that all of them provoke, or may provoke, a hyperimmune response, otherwise known as a cytokine storm (CSS). The clinical features of this have been well-described over several decades. The features of this include pulmonary damage with fluid loss into the air sacs or alveoli, clotting problems leading to bleeding (Hantavirus was originally known as Korean Haemorrhagic Fever), cardiac damage – specifically myocarditis – renal damage probably as the result of both inflammation and haemorrhage, and inflammation in the brain, or clotting/bleeding problems including stroke.
If anyone is in any doubt about this, consider these quotes.
From Zanza C et al. Cytokine Storm in COVID-19: Immunopathogenesis and Therapy. Medicina (Kaunas). 2022 Jan 18;58(2):144.
A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-vs-host disease following allogeneic haematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors.
From Moore RA, Griffen D. Hantavirus Pulmonary Syndrome. Hantavirus Pulmonary Syndrome – StatPearls – NCBI Bookshelf
Pathophysiology of HPS includes the following:
Inhalation of the infectious virus can result in viral deposition in the alveoli or terminal bronchioles. Viraemia is likely generated after infection of alveolar macrophages or other primary targets, resulting in widespread infection of the pulmonary capillary endothelium.
Replication within the vascular endothelium does not have direct cytopathic effects. Instead, tissue injury appears due to the immune response and viral replication. Increased viral RNA causes a cytokine storm, ultimately leading to vascular permeability and pulmonary oedema. Upon the development of pulmonary oedema, multiorgan failure may ensue.
From Younan P et al. Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm. mBio. 2017 Sep 26;8(5):
Ebola virus infection is characterised by a massive release of inflammatory mediators, which has come to be known as a cytokine storm. The severity of the cytokine storm is consistently linked with fatal disease outcome.
We might also introduce this:
From Chousterman BG, Swirski FK, Weber GF. Cytokine Storm and Sepsis Disease Pathogenesis. Semin Immunopathol. 2017 Jul;39(5):517-528.
Infectious diseases are a leading cause of death worldwide. Sepsis is a severe clinical syndrome related to the host response to infection. The severity of infections is due to an activation cascade that will lead to an autoamplifying cytokine production: the cytokine storm. Cytokines are a broad category of relatively small proteins (<40 kDa) that are produced and released with the aim of cell signalling. Our understanding of the processes that trigger this tremendous amount of cytokine production has made dramatic progress over the last decades, but unfortunately, these findings could not translate yet into effective treatments; so far, all clinical trials targeting cytokine production or effects failed. This review aims to summarise the pathophysiology of the cytokine storm; to describe the type, effects, and kinetics of cytokine production; and to discuss the therapeutic challenges of targeting cytokines.
That last quote underlines the truth that CSS occurs in numerous infections, whether bacterial or viral. The point is made in the Moore quote that the pulmonary effects of infection do not depend on viral replication. Thus it may also be the case that suppressing viral replication may be ineffective.
The whole gamut of CSS can be explored in Cron and Behrens’ textbook Cytokine Storm Syndrome (Springer-Verlag, 2019) which I have been trying, unsuccessfully, to make our decision-makers read, as anyone who has read my previous articles may recall.
CSS can occur without any obvious infection. I have seen such a case. I am still not certain whether it was a genetic predisposition or a reaction to a drug, but the clinical features were identical to what is seen here: fluffy pulmonary shadowing on X-ray, skin haemorrhages and renal failure. It responded to steroids. Having seen this one case I was immediately able to explain that the cause of the severe illness provoked in a drug trial (of TGN 1412 at Northwick Park Hospital) was caused by the provocation of a CSS. For details see Suntharaligam G et al. Cytokine Storm in a Phase 1 Trial of the Anti-CD28 Monoclonal Antibody TGN1412. N Engl J Med 2006;355:1018-1028. Likewise I have treated cases of severe bacterial sepsis with high-dose steroids, much to the dismay of some of my clinical colleagues, but of course with appropriate antibacterials as well. There may have been two mechanisms at play: a CSS and the unmasking of adrenal insufficiency – but that last bit is another story.
So let us return to our three bogey viruses. We have three somewhat different viruses that all end up producing the same common path – a CSS. Not, of course, in everyone. Why a small proportion of those infected get it remains unclear, although there is a genetic predisposition element, and it is possible that underlying immunological sensitivity may play a part. That said, if one has an underactive immune system, or immunocompromise, it might protect against the development of CSS – which is counterintuitive to clinicians brought up to believe that immunocompromise raises the risk of infection. That is likely, but the serious consequence of that infection – CSS – may be less likely.
If antivirals do not work (because they are not treating the CSS) and vaccination does not work (for the same reason, and because it is misdirected as the virus has changed) we are left with the inescapable. You treat the CSS. Steroids are cheap. Interleukin blockers such as tocilizumab and anakinra are not, but in the developed world not exorbitant for the relatively small number that need them.
The benefits of such an approach are several. No need for stockpiling useless antivirals (if you are not sure about this, I encourage you to discover the costs of flu antivirals that were ordered in bulk, did not work and were junked). No need for mass vaccinations (as they do not treat the severe illness of CSS, and there is evidence from the Covid saga that they have serious side-effects and may even increase death rates). No need for vast expenditure on protective gear (which may stop or reduce transmission, but to what purpose if it reduces the number of CSS cases from low to very low).
And that is the third thing SARS-CoV-2, Hantavirus and Ebola have in common. They cause widespread panic. Not necessary. Small earthquake, not many dead?
Dr Andrew Bamji is a retired Consultant Rheumatologist and was President of the British Society for Rheumatology from 2006-8. He blogs here.
Discussion
Comments
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Why is a cheap and effective treatment not used? Because it’s cheap.
“So vaccination might not be appropriate, or necessary.”
Shushhh! Ka-ching 💸
I wonder if the author has any sense of how many of his colleagues would broadly agree with this article. It would be interesting to know.
No, I don’t know, although medical friends I have spoken to have not faulted my logic. There’s always time. On the other hand there are many medics who not only refuse to listen to the facts but actively suppress debate (The BMJ now never puts up my “Rapid Response” comments) or worse persecute the so-called vaccine deniers by referring them the the General Medical Council, whereafter they are struck off the Medical Register. Admittedly the language of some is perhaps intemperate but I don’t think that’s enough to justify the punishment.. However as more and more evidence emerges about the shenanigans of the pharma industry over vaccine promotion, and also of vaccine harm, the balance may be shifting. It takes time. Look at the climate change debate!
Interesting. I was hoping that there might be a silent majority for the novel concept of treating ill people based on their symptoms among doctors, and that they may at least be prepared to admit to that to a trusted colleague.
Ahem…
‘Although the term “CS” was first coined in 1993, recognition of this hyperinflammatory state can be traced back to earlier literature, with references to an “influenza-like syndrome” in 1958 to describe the exaggerated immune response following systemic viral infections.’
‘Common colds, frequently caused by rhinoviruses (16), trigger 52% of relapses preceded by a defined event in patients with minimal change disease (MCD) or steroid-dependent nephrotic syndrome. While this relapse pathway is unpublished, we have considered cytokine storm to play a leading role.’
Worldwide studies show that 99.95% of age 70 or under survive covid, similar to common cold survival rates.
UK covid mortality average age almost identical with UK aversge life expectancy for both men and women.
SARS CoV 2 was a novel common cold coronavirus.
That’s it.
Agree. In fact you can go back even further. If you read the clinical descriptions of Spanish flu rapid deaths from 1918-22 you see CSS. It’s a rare complication so treat the complication and leave the rest alone.
Indeed. And the treatment for CSS, as the article indicates, has been well known for some time and is not expensive.
Rather than having an expensive backside covering inquiry, the top tier of the health profession in this country (Barrington Declaration signatories honourably excepted) and elsewhere should be questioned in an assembly of their peers as to why their response was so hopelessly incompetent…
It was novel i.e someone invented it, but SARS-CoV-2 doesn’t exist outside of a computer.
As someone who had Covid after 2 years avoiding it and after going on a boat with passengers coughing in my face, I can assure you that the symptoms are different from flu and the LFT tests worked. You need to speak to a psychologist. .
“What do all these have in common?”
All together now… THEY DON’T EXIST
Cytokine storms exist of course, but they’re not caused by invisible, non-existent pathogenic unicorns but by environmental toxins.
What occurred to me reading that was whether disruption of the immune system in that context is similar to what often happens (to me, and millions of others no doubt) in the context of allergies. E.g. at present, being troubled by grass pollen & similar pollen, I am less tolerant of other airborne compounds that don’t normally cause any problems. At least, there is a degree of over reaction of the immune system.
Anyway, if you search for the term “cytokine storm versus allergy” you will come across a lot of published discussion about the topic.
Another issue that is not covered here is the degree of opportunity in the trade encouraged by scary stories.
I deliberately avoided the trade opportunity aspect and stuck to clinical stuff. If you check out the blogs of Robert Malone, Steve Kirsch, Jessica Rose and Maryanne Demasi you will find quite enough about trade opportunity (particularly in respect of the sidelining of protocols for trialling gene therapies) to make you choke on your cornflakes.
I wonder if any of these ‘bugs’ have ever been isolated properly. i mean well and truly isolated and proven to be disease causing. Very tricky thing to do. True of any virus. should not only follow Koch’s postulates or even River’s postulates.
The answer is a resounding no!
Correct, viruses do not exist, no proof of dead RNA moving from animal to human has been offered since the time of that quack Jenner
Using gene therapy mRNA is most likely to initiate a Cytokine Storm response, but what the Hell, just offer it to everyone, and try to coerce, bully and cancel those who refuse – in clear contravention of international medical codes and ethics.