On December 17, 2020, Moderna submitted a 54-page document to the FDA containing the data from their vaccine trials. When compared to Pfizer’s original data, there are some obvious differences although the two are using the same technology and had a similar demographic and number of participants in their trials.
One of these differences doesn’t have to do with adverse events or efficacy data, (though I will be dissecting those as I update our guide, Everything You Need to Know about the COVID-19 Vaccine), it has to do with declaring the unknowns of this vaccine. Specifically the known unknowns.
The Beginning of the Unknown
Starting on page 48 Moderna lists “Unknown Benefits/Data Gaps,” these include:
- Duration of Protection
- Effectiveness in certain populations at high risk of severe COVID-19
- Effectiveness in individuals previously infected with SARS-CoV-2
- Effectiveness in pediatric populations
- Future vaccine effectiveness as influenced by characteristics of the pandemic, changes in the virus, and/or potential effects of co-infections
- Vaccine effectiveness against asymptomatic infection
- Vaccine effectiveness against long-term effects of COVID-19 disease
- Vaccine effectiveness against mortality
- Vaccine effectiveness against transmission of SARS-CoV-2
Although I would love to dig into each one of these unknowns, many of the above speak for themselves, so let’s just take on the important or more complicated issues.
1. Duration of protection
The vaccine trials only lasted for around 8 weeks. Moderna did not start counting cases until 14 days after the second vaccination. Therefore, it is impossible to know how long the vaccine-induced immunity will last, really, past 6 weeks. Vaccine immunity fades over time (please see my post on herd immunity for more on this), that is part of the reason we have an entire adult schedule although most people are vaccinated as children. So, without the proper length of time, it is impossible to say that COVID-19 vaccine-induced immunity will hold up longer than 6 weeks.
Let’s jump to number 3.
3. Effectiveness in individuals previously infected with SARS-CoV-2
This section states, in part, “participants with a known history of SARS-CoV-2 infection were excluded from the Phase 3 study.” Therefore, there is no way to know what kind of effect the vaccine will have on those who have had Sars-Cov-2 already. There may be no reaction as immunity has already developed. There may be an over-reaction, as we will discuss later. However, because there was no testing we have no idea how effective vaccinating those who have already had the infection will be.
Pressing onward to number 5.
5. Future vaccine effectiveness as influenced by characteristics of the pandemic, changes in the virus, and/or potential effects of co-infections
This one is the most confusing when first read. What it comes down to is that we do not know if this vaccine will work if and when the infection mutates or evolves. This is important because there are already reports of the virus mutating, and we have no idea if this vaccine will protect those who get it against these mutations.
6. Vaccine effectiveness against asymptomatic infection
This is where it gets very interesting, so I am going to let you read it for yourselves.
In other words, we do not know whether or not the vaccine will be able to stop you from having an asymptomatic infection of Sars-Cov-2. So, you may be vaccinated but you would not stop you from becoming an asymptomatic carrier. This is confirmed in the unknowns that follow.
Please excuse me for skipping a couple, we will come back to them.
9. Vaccine effectiveness against transmission of SARS-CoV-2
This section begins, “Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination.” Again, it is possible to get infected even after being vaccinated. As we have seen above, it is still possible to be an asymptomatic carrier after vaccination. This section specifically talks about the vaccine being designed for “symptomatic cases.” “Demonstrated high efficacy against symptomatic COVID-19 may translate to overall prevention of transmission.“
The study was not designed in a way that makes it possible to know the effect of the vaccine on asymptomatic cases. And again, as stated above, the efficacy against symptomatic COVID-19 cases may translate to overall prevention of transmission. This means it might prevent transmission or it might not prevent transmission at all.
We are also reminded here that even if you receive the vaccine you must continue to mask and social distance or the infection may continue to spread.
Going backward.. number 7.
7. Vaccine effectiveness against long-term effects of COVID-19 disease
This continues to confirm what we have said above, please pay particular attention to the highlighted portions.
We do not know if the vaccine will protect those who are still infected despite being vaccinated from long term health effects from Sars-Cov-2. This also reaffirms the fact that we have no idea if vaccination will stop those being vaccinated from becoming asymptomatic carriers.
8. Vaccine effectiveness against mortality
Lastly in the unknown benefits category, we do not know if the vaccine will have any effect on the number of people who are dying from Sars-Cov-2. Since most of those who pass away due to SARS-CoV-2 have multiple health conditions and are high risk without the data on the effectiveness of high-risk people, we do not know whether vaccination will prevent these deaths.
Further on in the document (page 50), we come across a section labeled, “Unknown Risks/Data Gaps.” Let’s take a look–
- Safety in certain subpopulations
- Adverse reactions that are very uncommon or that require longer follow-up to be detected
- Vaccine-enhanced disease
We will start with number one.
1. Safety in certain subpopulations
There is not enough data to know the safety profile of the vaccine in those younger than 18 years of age, pregnant and nursing mothers, or immunocompromised individuals.
2. Adverse reactions that are very uncommon or that require longer follow-up to be detected
There is the possibility of having long-term reactions to the vaccine. It does not list what these possible long-term side effects may be although the FDA’s draft of possible side effects is quite lengthy. They do mention the possibility of Bell’s Palsy being one of these reactions. However, they do not know if there is a causal connection. This section is ended with a rather intimidating statement,
“Further signal detection efforts for these adverse events will be informative with more widespread use of the vaccine.”
In other words, we don’t really know but once enough people take the vaccine we’ll find out.
3. Vaccine-enhanced disease
This is probably the most interesting unknown of all unknowns. The statement from Moderna itself does not explain what it means by vaccine-enhanced disease. It most likely means a disease that can show up from vaccination long term. This is the reason that most drugs must be tested for 3 years at a minimum because we know that over time severe reactions can occur, even 8 to 10 years after use.
However, there is a reason that we have not come out with an RNA virus vaccine before now. Why do we not have an RSV vaccine, Sars vaccine, or MERS vaccine? It is because we have tried to create these vaccines in the past and failed. These failures were more often discovered during the animal trial period, which we skipped during these trials. However, they all had to do with the same problem, after being vaccinated the participants seemed fine, however when re-exposed to the same virus they suffered, what we can only guess to be some kind of cytokines storms and many of them died. This has been called antibody-dependent enhancement in the literature, or ADE.
This has happened with vaccines that were given to the public before, it is a possibility with COVID-19 vaccines as well. However, as this section states, we do not have evidence from Moderna’s trials that this will happen. It is still unknown.
What does it all mean?
I chose to go through the unknowns listed in Moderna’s data because it is important that we acknowledge that there is still so much we have yet to learn. The majority of the population is likely unaware of these unknowns so we must recognize that we are still in the middle of this experiment. And although Pfizer did not give us such a clear cut view of what is unknown in their product, we can assume that most if not all of these unknowns apply. Both trials had a similar time length, number of participants, demographics, technology used, and Pfizer has not shown enough data to counter-act these unknowns.
People deserve to have full informed consent of what we know and what we don’t know so they can make their own educated decisions.
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