Or perhaps in other words “the end of the pandemic is nigh!”
I was about to write a blog about Covid-19 and mink farms… catchy I know… or the environmental effects of plastic aprons and gloves… and then I saw in the news that we have a Covid-19 vaccine that is 90% effective and we’re all saved! The mink are going to have to wait a while….
Now I’m all for a good news story about Covid-19; goodness knows we need one. But I’m also a sceptic and I look at all of these announcements about “game changing cures, treatments and preventions” in an increasingly cynical light. Just look at all the wonder cures for Covid-19 we have been told of by press releases so far; Hydroxychloroquine, Chloroquine, Azithromycin, Lopinavir/Ritonavir, Remdesivir, convalescent plasma, monoclonal antibodies, Tocilizumab and even Ivermectin to name just a handful. Of these only Remdesivir has been shown to make any difference so far, and then only by reducing duration of illness; some of the others have actually been shown to result in serious side-effects without providing any benefit. The only treatment we have so far that reduces the number of people who die are corticosteroids, which reduce mortality in the sickest of patients. So, please excuse me for not jumping up and down without first looking at the detail… I’ve been disappointed before and just can’t take it anymore.
The Pfizer Vaccine
The Pfizer vaccine is an mRNA vaccine, but what does this mean?
Essentially the vaccine triggers an immune response to messenger RNA or mRNA.
Each cell has DNA, the mRNA is the code produced when a cell is deciding what the DNA of a gene needs to “say” to the ribosome in order for the ribosome to know what protein to produce. Some viruses, including SARS CoV2 don’t have DNA instead they hijack the host cells reproductive mechanisms to produce mRNA without the need for DNA, like changing a DNA trait in a test tube baby…well kind of…anyway! The outcome is still the messenger passing on the blueprint; mRNA is the fundamental instruction to the cell as to what protein to produce. The vaccine messes with the messenger’s ability to pass the blueprint on.
It’s perhaps worth noting here that there is no mRNA vaccine currently in use for any other infections or diseases in humans… a small point but important, we haven’t already done this before because it’s tricky to do!
The Pfizer vaccine trial
You may want to take a look at the Pfizer Covid-19 vaccine trial protocol… but then again its 146 pages (with only 1 page of references) so maybe you don’t, unless you really do have trouble sleeping! Don’t worry; I have waded through the documented picking out the key bits for you. Aren’t I good too you!
The Pfizer vaccine trial is a randomised placebo-controlled observer-blinded study… what the heck is that?! Okay, they are comparing their vaccine against a fluid that contains nothing, participants randomly assigned to a group and those analysing the results don’t know who has been given what. BUT the giver of the vaccine does know and this could mean a degree of bias could creep in. It is important to note that it isn’t fully blinded, where nobody knows who’s been given what until the end of the trial. Fully blinded randomised trials are the most reliable against researcher bias, although I am sure with the World’s attention fully on Pfizer for a quick “satisfying” result they would never be biased in any way, would they!? My concern is that Pfizer have been “known” for their less than ethical behaviour, having previously paid billions of dollars to settle multiple lawsuits worldwide! The most notorious was the drug Trovan given for meningitis in Nigeria where “the drug trial was set up quickly and under hasty conditions to take full advantage of the outbreak”… sound familiar?
Anyhow back to the wonder “90% effective” vaccine. The aim has been to recruit males and females aged over 12 years with no upper limit on age. Only people who say they have never had symptoms of Covid-19 and who have not had a positive SARS CoV2 PCR test are eligible to enter the study. The study will continue until there have been 164 cases of Covid-19 across the study. Weird number; why 164 cases? Not sure but there has hopefully been some kind of statistical calculation done to work out that this number is what is required to decide if the vaccine works or not.
Participants are given 2 doses of vaccine 21 days apart. They are then checked at 1 month, 2 months, 6 months, 1 year and 2 years to see if they have developed Covid-19, as well as at the time of any ad hoc illness where they test positive for Covid-19 outside of this time scale.
The Pfizer vaccine trial started recruiting participants on the 27th July; so far 43,538 people are enlisted in the trial. They have reached their first interim analysis (at 94 cases of Covid-19 detected) and an independent team have looked at their results so far.
So, what we are seeing today is in fact analysis based on JUST the first 1 month’s results; it is still very early days in the trial. I for one would like to wait a bit and see what occurs at the 2 months, 6 months, 1 year and 2 year data points. Remember: this isn’t a challenge study “give the vaccine and then the virus and see what happens” as most people feel giving a potentially fatal disease to someone (even if you have “vaccinated” them) is unethical. So there is no way of knowing if the trial participants have actually come into contact with the virus yet. The "results" presented “so far” are that there is a higher rate of infection in the non-vaccinated group compared with the placebo group, but we do not know yet if the level of exposure is the same between the groups. For example, if this was occurring in the UK and all the vaccine group are in the Southeast of England and the placebo group are in the Northwest (NB no government graphs here!!) then the exposure to SARS CoV2 will have been much higher in the placebo group because the incidence is higher in the Northwest. Pfizer have not given this level of detail…yet!
What is good in the trial so far?
So, let’s look on the positive side; there is the potential for a vaccine against Covid-19. This really is good news, AND the data is being reviewed by an independent team, the Data Monitoring Committee… not just Pfizer.
One of the other good things in this trial is that they are looking at how the vaccine works in all ages over 12 years old. We don’t know the exact ages of the participants, but it is especially important to know how this vaccine is going to work in older adults. As we get older our immune systems don’t work as well, and this also applies to how effectively we react to vaccines; it’s known as “immune senescence”. Older people may not become immune following vaccination, so the vaccine must be tested directly in the older age groups to get this data.
Another good thing about the study is that they are looking for evidence of infection in the participants irrespective of whether they have had symptoms or not; blood is taken at every visit/data point after vaccination and tested for antibody against both the vaccine as well as the natural virus. If vaccinated, participants have both antibody against natural virus and the vaccine then they have been infected even if they have been vaccinated. This is important as the vaccine may lead to milder/asymptomatic infections meaning those who have been vaccinated could still be a potential source of transmission of the virus. This would make the vaccine less useful.
OK so I haven’t said “much good” but then Pfizer haven’t actually told us anything! There is no paper yet, so there is no peer review of the data…in fact there is no data at all!? It’s just a press release.
What are the problems in the results so far?
Well for starters we have just been told it works… we have seen no evidence!
There is no comparison data for the 2 groups so we cannot tell if they really are equivalent in terms of risk etc. Have enough “older people” been studied, is the gender balance adequate, are enough people from different ethnic groups included to say the vaccine works in “everyone”. Without the detail we just must take Pfizer’s word for the results and that can be prone to bias. Show us the data!
A vaccine that only makes 90% of people immune (which is what we assume they mean by saying the vaccine is 90% effective) may not be enough to prevent SARS CoV2 circulating in the community. We normally look for at least 90% immunity in a population to stop a virus circulating therefore if a vaccine is only 90% effective at inducing immunity we would have to vaccinate everybody, e.g. the whole population, to hit this magical 90% target. Getting 100% vaccine coverage has never been achieved before, so 100% just may not be achievable; logistical nightmare plus the vaccine up take might never be 100% possibly due to anti-vaxer’s fears/philosophies, those who are allergic and safety in children concerns (only tested in the over 12s) etc.
We also don’t yet know how long the protection will last from vaccination. Natural infections with coronaviruses do not tend not to give us full long-term immunity e.g. it is possible to “catch the common cold” coronaviruses more than once, we don’t have immunity for life. Now it may be that this vaccine is more immunogenic and does give long-term immunity, we just don’t know. Pfizer only have 1 month of post vaccination “data” so far… they need a lot more information to know how well this vaccine will work over time.
Added to this Pfizer do not yet have the data on the vaccine’s safety “Submission for Emergency Use Authorization (EUA) to the U.S. Food and Drug Administration (FDA) planned for soon after the required safety milestone is achieved, which is currently expected to occur in the third week of November”. As it’s only the 12th November today this “required safety milestone” has not actually been reached, although positively there has been no serious safety concerns reported so far.
Unfortunately the study is also not fully blinded, so there is the risk of bias in the observation of results. The placebo may be obvious (cloudy vs clear or leaves no local symptoms vs. a hive etc.), this means those involved may actually be aware of who has had the vaccine and who hasn’t. In the Oxford vaccine study, instead of using a placebo the investigators have used an alternative vaccine, against the bacterium Neisseria meningitidis, as the control so that any local reactions from receiving a vaccine occur in both groups of the study and therefore it will be impossible to tell who has had which vaccine.
Then there is the deep freeze issue, which was NOT disclosed in the original press release but the press are all over that! The vaccine needs to be kept at -80 degrees centigrade (freezers like this cost approx. £4000-9000 plus, that means it would cost about £70 million for every GP practice in Britain to get one!). A home freezer is only -20 [No ECIC you cannot store the vaccine at home next to the turkey!], we have a -80 freezer in the laboratory to keep organisms in long term storage and allow bio-recovery… but will your local GP health centre have one? Matt Hancock (Health Sectary) has announced “GP’s are gearing up” to deliver this vaccine program? Really!?!, GP’s DO NOT have this capacity… but I know, let’s get those clever 3D printers back into action… they must be able to produce a -80 degree freezer for less than $10… if we believe the media (BBC), they can already print ventilators… can’t they!? Umm well actually no they can’t, “this” is not a ventilator as used in a hospital ITU. This is a “bag on a bellow” akin to it being made on Robot Wars! Why do we spend so much effort on these “Heath Robinson” ideas that are non-starters and nonsensical!?
Another potential reason for bias is that Pfizer will want to be the first to market; their share price has climbed nearly 10% based on this press release alone! Let’s be honest there is a lot of money at stake. But just look at the response to the news for other companies; Ocado who is delivering your lockdown groceries during the pandemic their shares are down, all that DIY madness this Spring – yep DIY supplier’s shares are down, Dettol shares are down and even the company manufacturing Remdesivir for Gilead is down… it’s a strange World!
Pfizer say they can produce 50 million doses of vaccine by the end of this year… that’s not much when you consider that will only vaccinate 25 million people. But they also say they can produce 1.3 billion doses by the end of next year and that is much more impressive! Yet that’s still short of the 7.7 billion needed for the World’s population.
What would be even more impressive is if Pfizer gives the formula away for Worldwide generic manufacturing!! “Hang-on my pension might be tied to Pfizer!?” Gosh, conflict of interest and an ethical dilemma!!
So, the announcement of a vaccine against Covid-19 IS great news for science and humanity, but we need to employ some cautious optimism. So far what we have been told is promising but we really need to see the raw data and extend that data out to many more people over a much longer time scale. In the words of Fox Mulder, from the TV show X Files, “I want to believe”… but I’m not going to sell my shares in Ocado/Dettol/DIY firms etc. just yet…