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COVID-19 mRNA vaccines – what does the initial data show?

COVID-19 mRNA vaccines – what does the initial data show?

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How many COVID-19 vaccines are out there?

This article is about the new vaccines that are coming out. Some of these vaccines are the first of their kind, with the type of technology that has never been used before to mass-inoculate people. This potentially means new risks and we will discuss some of these, and compare them with what the first public data looks like from both the clinical trials prior to the public roll out of these vaccines, and then after the roll out.

This article does not have an agenda to support a vaccination program nor to vilify it. Meaning Merogenomics is not married to a camp of anti-vaxxers, nor those who think everyone should be vaccinated (because not everyone is actually eligible to be vaccinated), and so the main purpose here is to produce an article of interest to everyone – whichever your school of thought. Each group has a message important to them: from pro-vaxxers it is the need to support public health efforts, and from anti-vaxxers it is the fear associated with a product that could potentially produce harm. Both camps argue about harm, but one group refers more to public harm while the other refers to individual harm, yet both arguments need to at least be heard, irrespective of what science supports, because clearly if concerns exist, they have not yet been properly addressed in the general population. Both sides need respect if we are to make the smartest public decisions moving forward, which we believe can only be achieved with quality education about the available information.

Image of Merogenomics article quote on pro-vaxxer and anti-vaxxer concerns about health

To start, there are many COVID-19 vaccines in development; a whole array! Right now, everyone is talking about the Pfizer/BioNTech vaccine (for now called BNT162b2) as that was the first one to be approved for use in the UK and in the US (and now in Canada), and is the much talked about and much anticipated, first-of-its-kind mRNA (mature RNA) vaccine. Right on the heels of Pfizer/BioNTech, another mRNA vaccine was approved from Moderna (for now called mRNA-1273). But on top of these there have already been vaccination programs started in Russia and China using their own domestic efforts and numerous other vaccines are all in the pipeline and awaiting approval using the more traditional approaches in vaccine development.

While never previously approved for human use, in theory the mRNA vaccines should be some of the safest vaccines ever, because the mRNA lifespan is very transient. Once we inject it into our bodies, it will be degraded and cleared out of our body in a short time frame after it is used to produce a specific protein that is also found on the virus. The lifespan of the proteins produced from the injected mRNA is also going to be transient, eventually earmarked for degradation by innate cellular processes, but before the complete disappearance of any evidence that a vaccine was ever injected, the proteins produced from the mRNA template will elicit an immune response that should prime us to fight the real infection later in the future.

Image of Merogenomics article quote on mRNA vaccine safety

But because these vaccines are brand new, their use is fraught with some public fears. Let us break these down one by one and dive deep into the available science on these new vaccines.


Fear #1: lack of long-term data

This is truly the thorniest issue in the argument between public safety and individual safety. There are certain risks we have to take if we want the fastest solution possible and there is simply no way around it. The world has produced not one, but multiple vaccines in under a year to address a global pandemic, a feat that many pundits proclaimed would be impossible. But here we are, a feat that really is comparable to landing humans on the moon for the first time. The world wanted the fastest solution. You got it! But this means it has to come with certain risks and unknowns precisely because there has not been enough time to investigate. Certain information can only come to light over the passage of time. So, we all need to agree on that. Thus, long-term effects of this vaccine are completely unknown, and cannot be known until that long period of time elapses. It will take us many years of observation to discover any possible nuances related to both the COVID-19 disease and how to best protect us from it with minimal harm.

This is also the biggest risk that we are taking when accepting the use of this vaccine. In medical research there have been many stories of promising results but with short-lived consequences. There have also been stories of promising initial results with terrible consequences on a mass population. We all acknowledge that has happened in the past and we always hope the future will continue to get better with better results. That is why people are brave to take risks. Of course, we are all faced with attempting to solve this global pandemic that is not slowing down.

Anyone taking the vaccine should be aware of that simple fact that these vaccines were produced in record time and therefore any long-term data on expected effects or undesired side effects is missing. We applaud those taking the vaccine as brave heroes wanting to take that risk to discover those effects. We should be proud of those who are willing to take the vaccine. But at the same time, we should acknowledge that the fear of long-term unknowns is very legitimate, and respect the fact that someone could elect not to take the vaccine on these grounds, for their own personal safety. It is not like we are about to inoculate the entire world (although enough production capacity has already been put in place to be able to vaccinate all adults in the world and the speed of the roll out of the vaccination is breath taking!), and many choose to wait for more data from the current brave volunteers. That actually makes sense. We survived fairly intact in terms of total human lives for this global pandemic. We as a humanity have been very lucky that the COVID-19 pandemic was not more deadly than it was. It could have been worse, but the world reacted in unison to protect the world. These new fears are very reasonable in that we are dealing with a new kind of vaccine that we have never studied before, the mRNA vaccines. This fear cannot just be dismissed as belonging to anti-vaxxers, it is also commonly reported by people involved in the areas that deal with vaccination all the time, such as healthcare workers and doctors as well. This fear is motivated simply by the complete lack of long-term data but paradoxically the data can only come to light by moving forward with the vaccinations.

Image of Merogenomics article quote on mRNA vaccine safety

In the meantime, with each passing day, month and year, we will be assembling long-term data on the consequences of mRNA vaccinations to help alleviate those concerns.


Fear#2: immediate harm from vaccine due to side effects

This area is where we actually do have some data, and by now, data from thousands of individuals, both thanks to the clinical trials performed prior to the vaccine roll out, as well as information coming in on what is happening to people who are willing to take the COVID-19 vaccine.

The good news is that the vaccines are appearing very safe based on the FDA information that has been made publicly available. The clinical trials show that there are no serious side effects, and the side effects observed are typical for a vaccine’s use including tiredness, headache, muscle pain, and chills.

But clinical trials by their very nature are going to be limited. The true experiment with the use of the Pfizer/BioNTech and Moderna vaccines that will produce the most real and valuable data is the experiment that is ongoing now, when the vaccines are being rolled out for public inoculation. The reason why is because any clinical trials, at most employ a few tens of thousands of individuals (who on top of that have to be split into treatment group and control group) which in the highly controlled environment of clinical trials does not necessarily replicate the real-world scenario (although of course the goal is to make it as “real” as possible). On top of that, when we say that the vaccine appears to be safe in the short term that they have been studied, we really mean “short” term. Of the Pfizer/BioNTech and Moderna vaccines, only ~50% of participants have been followed by 2 months or longer but it appears that there is no data yet for a 3 months period for any participants.

Case in point is that although no serious anaphylactic shocks were observed in the clinical trials, there were some observed immediately upon the vaccination roll out, resulting in both the UK and the US public health safety organizations releasing a warning about it. From the US Center for Disease Control and Prevention (CDC), anyone with past history of severe immune reactions to any components of current COVID-19 vaccines should consider avoiding the vaccine. Ha, we wonder how many people will inspect that information! If you need it, here it is on the government of Canada’s page on the Pfizer/BioNTech vaccine - and by the way, the first three scary sounding non-medicinal ingredients are lipids that are used to create a transport bubble in which the RNA is housed. This is very important though, because anaphylactic reactions can be extremely dangerous and lead to death. If you have a reaction to the first dose of the vaccine, definitely stay away from the second. If you have had past, severe immune reactions to other vaccinations or medications though, you are supposed to ask your doctor for advice, which sounds kind of dumb because that is delegating a responsibility to an individual that perhaps is not likely to be any further informed to know how to proceed safely . If you have had past, severe immune reactions to foods and other stuff, you are good to go apparently to take the risk of vaccination.

Image of Merogenomics article quote on COVID-19 vaccines anaphylactic reactions

This is in contrast to the vaccine warning issued from the UK, which stated that “Any person with a history of anaphylaxis to a vaccine, medicine or food should not receive the Pfizer/BioNTech vaccine.” That should exclude a good chunk of people then. So take your pick of which medical authority you would like to listen to. What the CDC proposes as the smartest approach is that if you did actually have any history of severe allergic reaction, to anything, inform the healthcare staff administering the vaccine to you to make sure they monitor you for bit longer than normal after you get your shot, 30 minutes instead of 15 minutes.

Luckily, the very early data from CDC based on 112,807 first COVID-19 vaccinations in the US reported only 6 such anaphylactic reactions, or 0.005% chance. This is probably why it was never seen in clinical trials because it is rare enough event that the clinical trials did not include enough people to learn this. In addition, CDC reported 3,150 people to have experienced side effects that sidelined them from normal activities. That is 2.8%. These are expected to be short lived only. The important news is that in the short term, these new experimental vaccines appear very safe.


Has anyone died in the COVID-19 vaccine clinical trials?

The answer is yes, but it had nothing to do with the vaccination itself as far as could be determined, so it is better it is mentioned before you read it somewhere else out of context. In the Pfizer/BioNTech vaccine trial, in total 6 people died. However, as the report issued by the FDA on the Pfizer/BioNTech vaccine stated, “All deaths represent events that occur in the general population of the age groups where they occurred, at a similar rate.” These were not deaths with unusual presentations. 4 of these were in the placebo group and 2 in the vaccination group. In the Moderna vaccine trial, 13 people died, 7 in the placebo group and 6 in the vaccination group with same conclusion as for the Pfizer/BioNTech.

However, it is very likely that eventually we will see someone die from taking a vaccine, and when you inoculate the entire world, this is to be expected that unfortunate twists of biology will take place. Unfortunately medical treatments lead to high number of deathsand that is the reality of the world we live in. But we do not want to not have our doctors around, or our medical system when we need it. It is always an ever-evolving system that is constantly improving medical care but this has risks attached. We all have to accept that risk if we want to participate in it. Just like we all have to accept the potential risks if we do not participate in the medical system that we currently have.

 Image of Merogenomics article quote on vaccine risks


Fear #3: a completely new experimental design of vaccines that has never been tried before

There are multiple vaccines coming out. There are at least four different COVID-19 vaccines already being used around the world to inoculate the public, but the first two to hit the market in the western world are of the type that has never been tried before. EVER! The first of its kind, it has only been discussed on theoretical grounds. We have discussed what is RNA extensively. Here is great background on mRNA COVID-19 vaccines from The New York times.

Basically - with these new vaccines we are mimicking how our cells normally work by producing a tiny template in the form of RNA that is copied from the DNA (which is the repository of all information), and the RNA blueprint (once it has been processed, it is referred to as mature RNA or mRNA) is used to produce a protein of interest for the cells to use. The difference here is that the protein of interest that is produced is the alien spike protein that is found on the surface of the SARS-CoV-2 virus. The other difference is that the mRNA information is not derived from our genome, the DNA repository, but injected into us as a form of vaccine, in specialized bubble (these are called vesicles or you might have also seen them termed lipid nanoparticles). Just like a soap bubble except the surface of the bubble is bit more complex than what you would find in a soap bubble, but to some degree similar, in that it can merge with fatty substances (this is why we use soap to wash our hands, and why it is such effective killer of the virus, as it will disrupt the fatty membrane of the virus). This ability of merging with fatty substances is what allows these specialized vaccine bubbles housing the mRNA instructions to fuse with the fatty membrane surrounding our cells, and release the mRNA content inside the cells. Once inside the cell, the vaccine-derived mRNA is used just like any other mRNA that our own cells produce. It is used as a template to produce a protein, in this case the SARS-CoV-2 spike protein.

 Image of Merogenomics article quote on how does the COVID-19 mRNA vaccine work

Proteins that are normally produced inside our cells are then either used internally inside the cell, alternatively they are allocated to reside on that outside membrane of the cell, or they are excreted outside the cell. Wherever their final location, they will have some (hopefully fun) tasks to perform. The idea with the mRNA COVID-19 vaccine is that the cells that uptake the viral mRNA will end up producing the alien spike protein which will then end up on the surface of these cells, or be excreted outside. Once on the outside of the cells, our immune system can start recognizing it and mount an attack against it, and along the way, so we hope, produce long lasting immunity against any future invading spike proteins on the surface of the actual SARS-CoV-2 virus.

This all sounds amazing, and scientists have been fantasizing about this for a long time now. And there is lots to fantasize about here! But before fantasies, we wondered about one reality check item that we wanted to get feedback from some smart folks.


Antibody-dependent enhancement (ADE): immune system’s double-edged sword!

We already know from the past work with the original SARS-CoV virus that vaccines produced against that virus resulted in pathologic immune-reaction called antibody-dependent enhancement. We are talking about immunity-based enhancement of the disease triggered by the vaccination process itself. In essence, what happens is that the vaccine results in stimulating the antibody production against the infectious agent, in this case antibodies against the spike protein. However, not every antibody is created the same. Each person will produce their own antibodies that could end up targeting different areas of the spike protein with different affinity for interaction. Some antibodies will bind very strongly to the virus and prevent it from being able to interact with our host cells and invade them. We call such antibodies “neutralizing antibodies”. But if the randomly produced antibody binding is weak and not well targeted to permanently inhibit the virus from being free to do its dirty bidding (invade our cells and replicate itself), then our body will not only have a hard time clearing such viral infection, such antibodies can also inadvertently help the virus infect even more cells. We call such antibodies “enhancing antibodies”.

How does this happen?

Some of our immune cells are supposed to uptake the virus bound to our antibodies by catching that antibody, and destroying it all inside the cell. But if such a cell takes up the complex and the virus becomes free inside these cells, then in essence these cells end up being infected themselves as opposed to destroying the virus. Past studies have shown that some such enhancing antibodies can bind the spike protein and induce uptake of the entire complex (the infecting virus with antibody bound to it) with the virus surviving and happily replicating inside the victim cell, thus promoting the virus infection inside the host. The virus uptake and infection of certain cells is accidentally enhanced by the antibodies. This phenomenon has been observed for number of other respiratory viruses in addition to SARS-CoV, and has plagued past vaccination attempts. Thus, the concern with regard to SARS-CoV-2 is legitimate.

 Image of Merogenomics article quote on virus antibodies impacts

Another possibility is that the enhancing antibodies produced by the vaccine could help produce a specific immune chain-reaction during the real virus infection that could enhance inflammation and immunopathology. You might have heard of this being described as a cytokine storm, and it has been observed in some of the severe cases of COVID-19. Perversely, the immune reaction that is elicited is so strong that it ends up leading to further damage, like inflammation of the lung tissues, closing of the airways and even death.

Therefore, any vaccine that relies on the production of full spike protein, like these new mRNA vaccines, in theory could bear the risk of antibody-dependent enhancement. So how have these potential safety issues been addressed?

This is not some theoretical concept for COVID-19 vaccines. Recently a report was published demonstrating exactly that same scenario, where actual COVID-19 patients’ antibodies (produced by the SARS-CoV-2 infection) were found to actually promote viral infection. Currently, this is still a preprint and hence awaits peer review, but it is the first proof of this concept with regards to SARS-CoV-2.

Thus the risk that a vaccine could lead to the production of similar infection-promoting enhancing antibodies is also very real. This concern over the use of the entire spike protein in the vaccine has been raised before by other scientists as well, precisely calling for using only a portion of the spike protein that is used in the binding of human receptors, the so called receptor binding domain of SARS-CoV-2 spike protein (see our previous post for details on SARS-CoV-2 spike protein), for the purpose of safe COVID-19 vaccine development. On top of that, the antibodies that actually enhance SARS-CoV-2 infection appear to bind to a very specific spot of the spike protein away from the receptor binding domain, and the authors of the above preprint actually mapped it all out! You can see it in the image below, with every amino acid of the spike protein involved in the epitope for the binding of enhancing antibodies indicated in red shades. Epitope is an area that is recognized by an antibody.

Merogenomics figure on enhancing antibodies epitope

Adapted from preprint

This means that very specific mutations could have been implemented in the mRNA vaccines to easily alter the epitope against these enhancing antibodies and thereby prevent or reduce the risk of antibody-dependent enhancement. But whether this newly discovered knowledge was taken advantage of in the mad rush to develop the mRNA vaccines is something we do not know, because the sequence code of the mRNAs used in the vaccines has not been made available for examination.

If these findings that have been already observed with other viruses, and now with COVID-19, that certain types of antibodies can elicit antibody-dependent enhancement of disease progression, then sooner or later we will see this as well with some of the patients who are vaccinated. Meaning, the vaccine will not only not protect the vaccine recipients, but actually enhance their chance of getting COVID-19! When the vaccine spike protein is present to elicit antibody production, our body’s random generation of antibodies against that spike protein will always run the chance of accidentally producing enhancing antibodies against the virus that will actually increase its infectivity. This could be rare, but it will happen. The only way to know it after vaccination would be to actually analyze the type of antibodies that are produced in the vaccine recipient, the same way that this phenomenon was actually discovered in some past COVID-19 patients.

The authors of the preprint mentioned above also found that all COVID-19 patients that ended up being hospitalized that they studied, had some level of such enhancing antibodies (along with neutralizing antibodies)!

At this point, we could not agree any more with the authors' final conclusion. Further studies are required.

 Image of Merogenomics article quote on enhancing antibodies further research need


The exciting future emerging from this vaccine experiment

What Merogenomics actually finds exciting about the mRNA vaccines is that this is ushering a new era of genetic manipulation. In this case, RNA is used in a form of vaccine, where instruction to produce an alien protein is provided in order to elicit an immunological response. But we could just as well introduce any RNA of human origin, in a specific combination of numerous RNAs that together could start manipulating the biological behaviour of the infected cell. In fantastical theory, the extent of such manipulation is limitless, dependent on what instructions we want to be injecting inside our body. While perhaps we just might be uncovering the complexity of a sophisticated genetic expression inside our cells thanks to the advent of these next generation sequencing technologies, and we might currently be nowhere near ready for such manipulation, and the time will arrive where we will master this understanding, along with how to use more specific genetic instructions to manipulate our biology. In fact, we are progressing rapidly in understanding how genes work together to control cellular behaviours. You could envision a future where forthcoming medications are not synthetic chemicals, but genetic instructions to aid natural healing process. But if we are fantasizing, we can think of any scenario we want. Could we be manipulating aging? Could we be manipulating our cognitive or physical abilities? Could we be reversing effects of currently untreatable conditions? How would society choose to use such knowledge?

These are not just some wild notions. While the idea of manipulating our biological responses through the introduction of a concerted recipe of genetic materials might not be that common at this particular moment, the idea of inserting a variety of different RNAs as a single dose of numerous vaccines is here. There are ideas of a mass vaccination with a single injection using RNAs for all of the infectious agents that are of biggest threat to our collective health. Just imagine if that could work, that additional layer of enhancing medicine. The use of these new mRNA vaccines ushers in an entry of this new era of biological manipulation. We are truly entering a new frontier of medicine here where the portfolio of our ability to protect our health is about to be massively expanded.

 Image of Merogenomics article quote on medicine new frontier

So we are really hoping these new vaccines work, and work amazingly to help our collective health. First for the sake of all the current brave volunteers taking the vaccine. If successful, this will likely open the flood gates of some astonishing research moving forward.


Fear #4: is there enough data to support that COVID-19 vaccines even work?

One of the biggest concerns regarding the vaccine is whether enough studies have been performed to warrant its use in millions and likely billions of people. While the studies have involved many participants, which is great in terms of understanding what kind of side-effects can be expected in short term, what is perhaps not widely known is how few of the clinical trial participants actually ended up getting diagnosed with COVID-19. These were literally mere hundreds of people per trial, and those super high efficacy numbers of these vaccines were derived based on the difference of very few people infected in one group with placebo versus even fewer of those in the group with a vaccine.

 Image of Merogenomics article quote on COVID-19 vaccine research

Basically we are extrapolating the results based on few hundred infected people to use a vaccine on billions of people. And that is a one giant leap! One has to wonder how safe is it to extrapolate possibilities on such enormous numerical scale.

To give you an example, let’s look at the Pfizer/BioNTech vaccine. Each group that was tested (getting vaccine vs. placebo) consisted of around 20,000 participants each. In the placebo group, 162 patients were confirmed to get COVID-19. In the vaccine group, only 8 patients ended up with COVID-19. Total of COVID-19 170 patients.

That’s it! Based on the fact in total we compared 170 patients with COVID-19, the approximate 95% vaccine efficacy was derived and the vaccine is being rolled out for mass inoculation! The results between these two groups is amazing, but it is a very small number of people. Very very small for such a big extrapolation as is expected around the globe. We better hope that these very very very few COVID-19 patients were indeed enough to determine if the vaccine is truly effective in preventing COVID-19 on a global scale. As that is actually a very low number of people considering that as of this writing it is estimated that there are just over 75 million cases of COVID-19 worldwide! Potentially we are witnessing the cruel irony of the effectiveness of the mRNA vaccines, that as a result we have so few people with COVID-19 in the vaccinated group, that it is at risk of high chance of error. You always need more patients to increase statistical power. In the world of genetics this need has been recognized a long time ago. Health population studies in the world of genomics can now number in millions! That is what kind of numbers are analyzed to determine how accurate information could help predict future health outcome. Here we are down to single digits in the vaccine group. How many should it have been to be very safe before we start asking everyone to be vaccinated?

We will find out soon enough how that gamble went because we are about to get that sample data of millions! And the vaccine outcome will likely be very complex. Probably just as unpredictable as why different countries can be affected so differently by COVID-19.

 Image of Merogenomics article quote on possible vaccine outcomes

We see a similar pattern with the also just approved RNA vaccine from Moderna. The FDA analysis of Moderna vaccine results indicated that of more than 30,000 participants, 185 cases of COVID-19 were reported in the placebo group, and 11 cases in the vaccine group, for a total of 196 individuals. How many people actually found out that the vaccine that just has been approved and will be used on millions of people is based on results of 196 COVID-19 patients? Probably not many. What everyone heard was that these numbers were used to indicate that the vaccine is 94% effective.

But these are relative risk reductions, meaning risk reductions only in COVID-19 affected patients. If we were to look at the absolute risk reduction, which would include all the patients (the large number of clinical trial participants is also heavily promoted), then we are actually looking at less then 1% effectiveness.

What this is saying is that ok, fantastic, the vaccines are 95% effective against developing COVID-19 symptoms, but 99% of people in the trial did not need it. They never even got infected. And that has led to potentially statistically challenging very low numbers of affected COVID-19 patients in these trials based on which we are forced to make such enormous extrapolations.

Another way to put it though, if the clinical trial data was a reflection of a real world then as a world we are proposing one of the most daring and noble sacrifices humanity would have ever attempted: to let 99% of the population take a risk to protect the 1% vulnerable population. This is extremely humanitarian. Another way to also phrase it, we are looking at a possibility to vaccinate large portion of the entire global population to prevent approximately 1.5 million of global deaths due to COVID-19 in the next year. This will be the most noble kind acts the humanity has probably ever attempted. Noble acts are always seen as highly praiseworthy, positive signs. What is hard to understand is why as a humanity we cannot make such a united stand for events that are far more deadly to humanity than COVID-19? Wars take far more many lives every year. So do so many other health issues. We know that. But we justify this potentially risky move on account that the threat is global, and not localized. The entire world was affected by SARS-CoV-2 and the entire world was scared together. The entire world came together (except wars it seems but even they seem to have become more muted?).

Image of Merogenomics article quote on pandemic global threat

But if you look at the number of patients who were over 65 years of age, the primary target group of interest for vaccine as that is the highest risk group of dying from COVID-19, and the portion of the population that is going to be first in line to be vaccinated after healthcare force, then the number of participants in the clinical trials was ridonculously low. Here, our honest observation of that is that we are going to vaccinate a swath of our population based on almost non-existent data. It is like saying, hey, we did this study here with 10 people in one group and one person in the other. Based on the results of this test on those 11 people total, let’s vaccinate millions.

That is how little we apparently really know about the most vulnerable group. That age group with COVID-19 disease were almost not present at all in the trials because so few members of this age group took part in the trials, and almost none of them got infected. For this age group, we just have to extrapolate the benefits observed in the younger age group. The tiny number of COVID-19 patients in this age group support that same trend. It looks like we ended up overrepresenting the least vulnerable to COVID-19 at the enormous expense of underrepresentation of the most vulnerable to COVID-19. One potential reason why this mistake in planning happened is because the populations involved attempted to represent country demographics.

It certainly would have felt safer to have studies involving far more COVID-19 patients than that prior to asking or demanding a vaccination. However, we have to admit, this paucity of data related to actual COVID-19 patients did not seem to be bothering any of the regulatory health authorities in Canada, UK or the US when they approved these vaccines, so statistical extrapolation from few hundred to millions and likely billions must be all good? Surely estimating margins of errors of vaccine effectiveness of such extrapolation could be measured? Although we all agree we need to act fast. That is exactly what is happening. It just means it is very important to closely observe the incoming data so we learn much more, now, and fast!

By the way, those 162 patients in the control group of the Pfizer/BioNTech vaccine clinical trial comprised only 0.9% of the total. The 185 cases in the Moderna vaccine clinical trial accounted for 1.3% of the total studied population. In our last post, we discussed about the COVID-19 PCR test accuracy, the current gold-standard test, and that the test accuracy drops if the prevalence of the disease in the population is low. 0.9-1.3% of the population is low enough that if the test quality of the PCR used in these studies had false positive rate anywhere near this range, imagine how inaccurate that data would be! This is just one possible problem of using studies with such low numbers of actual infected patients. In this case, the PCR test was used correctly, to confirm symptomatic cases. Therefore, these low numbers reflect the fact that the PCR test was correctly used for diagnostic purposes of COVID-19, or those presenting with symptoms. As we reported in the last blog post, this is in stark contrast to how PCR is now often used for screening of asymptomatic cases.

Meaning, how trustworthy can be the claims of vaccine efficacy be when they are based on so few COVID-19 cases and we also know there is also a margin of error in the test for diagnosing COVID-19 as well?

Again, it would have been more comforting to have much higher numbers of COVID-19 patients being studied.

Image of Merogenomics article quote on vaccine study design

The only other vaccine study is for AstraZeneca-Oxford vaccine that currently is not yet approved. This vaccine uses the more traditional approach for vaccine development, where a modified virus is used to create a vaccine. The AstraZeneca-Oxford vaccine efficacy was shown to be 70% based on a study involving over 11,000 patients (both the vaccination and placebo groups) with 30 symptomatic patients developing COVID-19 in the vaccination group versus 101 in the placebo group. How much bigger do you think these numbers of COVID-19 patients will be by the time this vaccine is approved? We have a hunch that not much bigger. Again, a very small number of actual infected patients will determine the vaccination fate of millions of people.

By the way, of those 101 patients in the placebo group, 10 were hospitalized, two ended up with severe COVID-19 and one died. None of these were observed in the vaccine arm.

What was interesting about the AstraZeneca-Oxford vaccine study is that they actually reported the asymptomatic cases as well. In their study, the placebo group (representing our current status) had incidence of 1.2% of asymptomatic COVID-19 as compared to 1.7% of symptomatic COVID-19. But the vaccine efficacy in the asymptomatic group was only 27%.


What the vaccine trials could not answer

Due to the speed and number of participants, it is also important to note what these trials cannot provide an answer to at all until further studies come out.

The efficacy of the Pfizer/BioNTech or Moderna vaccine currently is only for a 2 month period as basically the trials could not provide longer term benefits. As the FDA reports on Pfizer/BioNTech and Moderna vaccines concluded, “it is not possible to assess sustained efficacy over a period longer than 2 months.” You can expect a similar limitation for the other vaccines that have already been approved or will be approved in a short order.

More importantly though, the Pfizer/BioNTech or Moderna data were not empowered to determine if those who had previously been infected with SARS-CoV-2 could benefit from the vaccine.

Image of Merogenomics article quote on if previously infected can take mRNA vaccine

The studies were also not empowered enough to provide information if immunocompromised individuals are safe to take the vaccine. No data was collected on children at all. Thus, we cannot even know if the vaccines are safe for children.

It also cannot be concluded if the Pfizer/BioNTech or Moderna vaccines are good for asymptomatic infections (we already know it is not that good for the AstraZeneca-Oxford vaccine).

Image of Merogenomics article quote on mRNA vaccines use on asymptomatic cases

It also cannot be concluded if the mRNA vaccines could protect you from dying from COVID-19. As the FDA reports stated (they really are exact same statements in each report), “Benefits in preventing death should be evaluated in large observational studies following authorization.” Or in other words, we are going to find out once we start vaccinating everyone.

Image of Merogenomics article quote on mRNA vaccines protecting from COVID death

The mRNA vaccines studies also do not answer if the vaccination can reduce the rate of virus transmission from person to person. Again, from the FDA reports, “Additional evaluations including data from clinical trials and from vaccine use post-authorization will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, in particular in individuals with asymptomatic infection.” This one might take some people by surprise as people tend to think about vaccination in very stark viewpoints, it either works by completely protecting you (the pro-vaxxers) or its use carries too high individual risk for proclaimed benefit (the anti-vaxxers), when the reality is a blend of benefits and risks, and the authorizing bodies have to come to the best conclusions with the available evidence to determine if the benefits outweigh the risks for the overall population. Thus technically, the vaccine does not necessarily help you from getting infected at all. It just might ensure that once you are infected, you will not develop COVID-19. Which we also will all agree we want that benefit if it is true! And logically you expect that if the virus is struggling in finding hosts for replication, and the fewer people can be found with COVID-19, then there is less virus likely circulating in that population, and that should result in a lower transmission rates.

Image of Merogenomics article quote on mRNA vaccines and infection

And finally, since no data was collected on pregnant women, we also cannot state if it is even safe to vaccinate while being pregnant.

Image of Merogenomics article quote on mRNA vaccines safety during pregnancy

The take home message is that we have to make compromises if we want to act fast. There is no way around it and as a consequence there are some still unanswered questions regarding the ultimate safety of the COVID-19 vaccines. We have to decide which risk is greater to face, the risk of infection or any yet unknown risks associated with these experimental vaccines?

The world wanted ultra rapid production of the vaccine. The world got it. There might be some risks associated with the vaccine that we just cannot know. But we already know of the risk of infection and the risk of death for different age groups. If we wanted a safer approach, we would have to wait longer for the vaccines to be available. That certainly would have resulted in more deaths attributed to COVID-19. Now is the time to decide: the risk of SARS-CoV-2 infection and potential death, or the risk of unknown consequences from experimental vaccines with no deaths recorded in at least in well over a quarter million people inoculated in the US alone already (measured in a span of only about two weeks). And no reported deaths in the millions already inoculated in the Russian and Chinese efforts.

Choose your fear. We cannot complain about both at the same time. Or we could and wait until either more data comes out related to the current vaccines, while continuing to take the risk of SARS-CoV-2 infection, or until another yet unknown solution emerges.

Each person now decides.


This article has been produced by Merogenomics Inc. and edited by Jason Chouinard, B.Sc. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.


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