That Time Of Year Again.
If you have read the previous two articles then you will know the main differences between a vaccine and an antiviral, and why Remdesivir is not an effective antiviral for just about anyone with COVID-19. We have highlighted that antivirals have a pretty patchy record when it comes to their efficacy, which is unsurprising given a) their therapeutic nature so they are not designed to be prophylactic and b) the fact that they are intended only to reduce the severity of infection once someone has already got the virus in question, meaning the antiviral is tampering with the immune response that will already be underway.
As we move into the traditional period when seasonal or winter flu (A(H1N1)/(H3N2)) is active, it is worth reflecting on the main therapeutics that make up the ‘flu jab’.
It is worth highlighting that we didn’t have a seasonal or winter flu outbreak in the UK last winter, principally because SARS-CoV-2 either crowded it out or gained its furin cleavage site from an influenza A serotype in its most recent recombination and so was last year’s seasonal or winter flu. This is something we have been writing about for over six months, for example in this article from 7th September and this article from 6th July.
The two main antivirals given in the UK are oseltamivir (Tamiflu on the packet) and zanamivir (Relenza on the packet). These are so-called neuraminidase inhibitors, with neuraminidase being the N in H1N1 (the H being haemagglutinin). Neuraminidase is an enzyme that assists in the ejection of newly-replicated virions from infected host cells, as well as smooths their exit from the respiratory system.
You’re Going To Need A Bigger Medicine Cabinet.
After the 2009 influenza pandemic, the Wuhan Huawei Occult recommended that countries stock up on their medicine cabinets. After all – as we have previously highlighted – the 2009 pandemic infected between 10.2% and 20.4% of mankind but managed to kill just 18,449 people. Yet another killer virus of death that infected many but killed very very few. Although Clown To The Stars Neil Ferguson predicted it could kill 4,000,000 (as always, if you fancy a laugh you can read more of Mystic Neil’s comedy predictions here).
There followed a bundle to get hold of the two main antivirals – Tamiflu and Relenza – with the large pharmaceutical companies obliging by offering lots of lovely snake oil antivirals in return for lots of lovely money. Nothing wrong with that but if you were stocking up on stuff at a national level and spending somewhere between £420 – £650 million of taxpayers’ money, you would want to know that the stuff worked. Especially since the death toll in England from the 2009 influenza pandemic was 138 (source: NHS), meaning that even at the lower end of the expenditure on antivirals for future use, the effective cost was £3,043,478 per fatality.
Question: If I gave you £3.04million and told you not to die from seasonal or winter flu, could you manage it and still give me back some change?
Cochrane Review.
A few years later, Cochrane (then called the Cochrane Collaboration) undertook an systematic, evidence-based review into the efficacy of these antivirals, which post-2009 pandemic had been touted as wonder drug antivirals by their manufacturers based upon the studies published by the manufacturers. Car manufacturer says their car is really good and worth every penny.
Cochrane is a charity that operates globally and exists to further the delivery of healthcare based upon making evidence-based decisions anchored in research. Entitled ‘Neuraminidase inhibitors for preventing and treating influenza in adults and children’ (the full report can be read here) – it looked at the evidence. Again, not sciency speculation or wacky speculation, not conditional voice ‘could’ but evidence-based or as it is also known, fact.
Crucially it looked at previously unpublished trials and confidential studies. From a starting point of 107 studies and trials, it identified that all the randomised control trials had been sponsored by the drugs’ manufacturers: just how random is a randomised control trial when it is organised by the manufacturer of the drug being trialed? The review narrowed the field down to 46 trials (26 on zanamivir and 20 on oseltamivir), covering 24,251 people, and considered the efficacy of the drugs in five areas:
- Duration of symptoms.
- Reduction in infection.
- Admission to hospital.
- Complications.
- Adverse side effects.
Their findings were:
Duration Of Symptoms.
In adults, oseltamivir reduced symptoms by 0.7 days and zanamivir by 0.6 days.
Reduction In Infection.
Both oseltamivir and zanamivir did reduce the risk of infection in individuals and households.
Admission To Hospital.
Oseltamivir had no effect on reducing admission to hospital. No data was available for zanamivir.
Complications.
Oseltamivir did not reduce serious complications. Zanamivir did not reduce complications.
Neither drug was shown to reduce the risk of secondary infection with pneumonia. Zanamivir but not oseltamivir did significantly reduce the risk of secondary infection with bronchitis.
Adverse Side Effects.
Oseltamivir increased the risk of nausea and vomiting in adults, as well as the risk of vomiting in children (as opposed to on them).
Both oseltamivir and zanamivir increased the risk of psychiatric event, including causing aggression and hallucinations. For oseltamivir, this response was present in 1% of those who were given the drug. 1% freak out or go nuts – who would even contemplate taking it?
Perhaps most worryingly of all, oseltamivir reduced the capacity of the adaptive immune response by significantly reducing the number of antigen-specific antibodies produced.
What Are The Scores On The Doors?
Oseltamivir and zanamivir reduced the risk of getting influenza A. In individuals the risk difference was very small – oseltamivir at 3.05% and zanamivir at 1.98% – although in households the risk difference rose to 13.6% and 14.8% respectively.
Oseltamivir and zanamivir reduced the duration of symptoms by approx. 0.6 days, down from 7 days to just under 6.5 days.
So in 2 of the 5 areas there was a benefit.
In 2 of the 5 areas – reducing the need to be admitted to hospital and preventing complications – there was no benefit (with the exception of zanamivir reducing the risk of developing bronchitis, even if a lesser illness that usually cures itself anyway).
In 1 of the 5 areas, both drugs increased the risk of side effects including some potentially serious side effects such as psychiatric episodes and of greater concern, inhibiting the function of the body’s adaptive immune system.
If you assigned +1 for a positive outcome, zero for ineffective and -1 for a negative outcome, you end up with (+1+1+0+0-1=) +1. Alternatively, given that the drugs were targeted to work in the five identified areas, a more accurate scoring methodology may be +1 for a positive outcome and -1 for an ineffective or negative outcome. On this basis, you end up with (+1+1-1-1-1=) -1.
Either way the benefits were hardly conclusive and certainly do not provide a ringing endorsement that these drugs are effective.
Review Conclusions.
The Review authors’ conclusions include:
“…it is unclear whether this is superior to treatment with commonly used antipyretic medications [paracetamol].”
“…did not find any credible evidence that either oseltamivir or zanamivir reduce the risk of complications of influenza, particularly pneumonia, nor reduce risk of hospitalisation or death. Moreover, even in individuals with a higher risk of complications, such as children with asthma or the elderly, we found no evidence of a beneficial effect for reducing risks of complications.”
Say what?! Those at high risk, who are THE target group to whom these antivirals are given to reduce the risk arising from complications – as it is the complications that will cause death – get no benefit from them.
“We urge people not to trust in published trials alone or on comment from conflicted health decision makers, but to view the information for themselves.”
NHS Conclusion.
Following their evaluation of the Review, the NHS’ own conclusion was:
“While it appears that these drugs have a modest benefit, there is no solid evidence that either drug can protect people from the more serious complications of influenza. Paracetamol or ibuprofen would seem to be a far more cost-effective method of relieving the symptoms of influenza.”
Current Relevance For SARS-CoV-2.
The rationale for setting out all this information is to show that a knee-jerk response to a stimulus – in this instant the stockpiling of antivirals following a pandemic – is unlikely to be effective. Not just because any impulse decision by a government involving money and drug companies is never going to end well but also because the drugs themselves are ineffective, offering at best modest benefit to some, no benefit to most and drawbacks to some.
As vested interests and conflicts of interests fall over each other in the stampede to develop a wonder drug (for the killer of virus death that continues not to kill people especially those it infects) bear that in mind.
There are valid reasons not to take nonsteroidal anti-inflammatory drugs such as ibuprofen to treat SARS-CoV-2 infection, as we have previously explained. If paracetamol is deemed as being as effective as the main antivirals in treating seasonal or winter flu, then how much more effective than paracetamol are any antivirals realistically going to be in treating a virus that is not as dangerous as seasonal or winter flu?
They will of course be much more expensive and will make lots of people lots of money, without ever having been exhaustively or transparently tested to the point that the evidence proves, to an indisputable confidence level, that they not only do work but also do not cause far more dangerous side effects.
“We urge people not to trust in published trials alone or on comment from conflicted health decision makers, but to view the information for themselves.”: not trusting conflicted health decision makers – something that reflects what we have been saying from day one of this Great Insanity.
Do not follow government advice.
