I made a discovery last year when I choose to jump out of a plane with my daughter on her 16th birthday. I tend to focus on the probability component of risk, my wife on other other hand focuses on the impact (which in the case of skydiving, is high both figuratively and literally).
I’d know we evaluate risk differently, but this activity just happened to finally clarify why we looked at things so differently.
It’s also the reason I’ve been reading about potential long term effects of Covid 19 vaccines. My wife wants to know the impact (if something goes wrong), despite the probability being very low.
However I don’t think my wire is alone in this, and it’s actually been very difficult to find good information (that a non scientist / medical professional can understand) on the real potential impact of mRNA vaccines (what could go wrong), and why those involved in evaluating the risk, believe the probability is low. (I spend part of my day job looking at risk, so I’m used to digging to the “whys”, as that tends to be where you find the real evidence, or lack thereof).
Anyways, eventually I did come across the following article, that was actually a very good description of how mRNA vaccines work & why the risk is low. I thought it might be of interest to other non-scientists.
The point can be summarized in a single sentence from the linked article:
The major problem with nucleic acid vaccines in general has not been their safety, but their efficacy.
In principle (a huge caveat), there should be less risk from an mRNA vaccine than from any other kind, because so many of the steps in making the vaccine and its eliciting of an immune response (which are known to produce side effects by other vaccines) have been skipped.
For me, as someone trained in virology, the risk is currently negligible relative to the benefit. That would hold true even if the efficacy was only 30%.
That could, of course, change with more data, but if I was offered either one today, I’d have my sleeve rolled up in less than a second.
NOTE: I should add a qualifier that it’s a no-brainer for me because I’m in my early 60s. I would still do it if I were just 20. For children, we might want to wait until there are more safety data.
How is this relevant to the Covid Vaccines?
Moderna claims their vaccine has an efficacy of 94.1% , Pfizer claims 95% based on initial studies.
Are these vaccines somehow fundamentally different?
I’m not a vaccine scientist, but I think these are just improvements on a relatively recent technology. The idea has been around for a while, but the attempts at engineering them have been scant. I think these may just represent the most recent iteration. It is also possible that this particular combination of spike protein/mRNA vaccine strategy is more effective than previous attempts. I just do not know of anything novel that would make these fundamentally different.
Given the transmissibility of SARS-Cov-2 you will have an mRNA for spike protein in your cells at some point or another, be it from the virus itself or from the vaccine. If there was a 0.1% death rate and an even higher morbidity rate from the vaccine we would have seen that already, and it hasn’t been seen.
I think it is much safer to get just one viral gene instead of the entire active genome, especially given the success of the trials thus far.
Personally I’m not worried about the vaccine. I’ll be getting it as soon as it’s available (though being in a pretty low risk category, it will be a bit, before it’s available to me).
I think the niggling question I still have is, how do we know that there are not side effects of the mRNA that won’t show up for months or years. For example, how do we know that the mRNA in the vaccine doesn’t create a second protein that over the long term has a negative impact. How does the testing being done, or the knowledge we have about mRNA make this an acceptable risk?
The concern regarding persistent mRNA is negligible. Most natural mRNAs in the cell half a half-life of roughly 5 minutes. The trick to an effective mRNA vaccine is to make sure it is stable enough to go through the introduction process and still be viable enough to be translated into the desired protein to elicit an immune response. The Pfizer and Moderna vaccines certainly seem to do the trick, but the mRNA will not last long. I don’t see any mechanism by which a second protein could be produced at all.
Other mRNA vaccines for Zika and Ebola and such have been in testing for years, so I think something like that would have shown up. But also, i don’t know by what mechanism that could even happen, since mRNA degrades so quickly (hence the extremely cold storage temps for vaccines).
As far as Covid-19 goes, we know there is a significant rate of long term effects from the disease (heart damage, symptoms that last for months, etc.). I don’t know what percentage it is, but it’s certainly much higher than the risk of long term effects from the vaccine. Tens of thousands of Covid-19 vaccines have been given, and I don’t think they’ve had any side effects beyond the initial “your immune system is working” that lasts a day or two? So with the current data, risk of disease is much, much, much higher than whatever theoretical risk of vaccine.
Unfortunately, the anti-vax misinformation machine is hitting hard right now. A friend of mine asked me the other day to find information about the mRNA vaccines and infertility, because her sister who is about to get married was freaking out after seeing something on Facebook. Thankfully, the infectious disease experts I follow on IG were debunking that one that evening, so I was able to send their explanations. These anti-vaxers are taking the “make a sciencey sounding explanation that’s total bunk” methodology to the extreme. God bless the science communicators who do such a good job translating science to laypeople.
How do we know the proteins produced by the mRNA only do what we want them to & have no other long term effects?
Is the answer simply that this an area of biology that is well enough studied that the experts can confidently say there are no mechanisms to produce these unexpected side effects?
As I understand it, with typical vaccines, I believe there are usually long term studies to watch for these side effects, before the vaccine is released.
Perhaps another way of phrasing my question is that I understand that given the risk of Covid-19, it makes sense to go ahead with the vaccines. But what actually gives us the confidence to say that the chance of long term effects is low enough we can bypass these long term studies.
Not questioning the choices being made, just trying to wrap my mind around the evidence used to make these choices. Mostly out of curiosity, and partly so I can answer people who might question the choices.
The assumption would be that the spike protein by itself would have essentially zero activity when a cell makes it since nothing else of the virus is present.
Yes, safety studies are typically longer, but as you say, the need is urgent right now.
The good news about Pfizer and Moderna vaccines is that these mRNA vaccines are the safest type available. Another aspect of these that can be important to a lot of conservative Christians is that their development did not require the use of any cell lines. From what you’ve mentioned in the past, I suspect there are others in your circle of influence that might have concerns about this (as some Catholic priests have expressed).
The mRNA that is introduced is transient, and the protein produced in response to the vaccine cannot be sustained since the mRNA encoded it is transient.
A vaccine scientist could definitely tell you more than me, but - like you - I’m confident enough to roll up my sleeve as soon as it is available for me.
The first trials started about 8-10 months ago, so if there were 1 in 10,000 side effects that show up over a span of months it would have shown up in those studies. If there are effects that don’t show up for years then people who have had COVID-19 will be susceptible to the same side effects. The mRNA vaccine is essentially mimicking a viral infection, so whatever risks there are associated with the spike protein in a viral infection will be the same for the vaccine. This will probably be true for all vaccines, mRNA or protein antigen, because they will all use the spike protein.
The only long term risk I can see is molecular mimicry where antibodies raised against the spike protein react to your own proteins. Quickly scanning the literature, there does seem to be reports of acute autoimmune disease associated with SARS-CoV-2 infections, but I have yet to see vaccine trial data where these same immune reactions are occurring. Is there a risk of adverse reactions with this vaccine? Absolutely, as there is with every single vaccination. The real question is the relative risk between the infection and the vaccination. If there is a 1,000 fold increase in adverse reactions associated with the virus compared to the vaccine then it should be an easy choice.
As others have mentioned, the half-life of mRNA in the cell is measured in minutes to hours, so it won’t be around long. The half-life of surface proteins is measured in hours to days, so the spike protein won’t be around long either. There simply won’t be anything from this vaccine left after a few days, other than causing the body to produce antibodies to the spike protein.
Coronaviruses aren’t foreign to humans, and we develop antibodies and immune reactions to them throughout our life. There is always a risk with each new antigen introduced to the body, but I don’t think coronaviruses are more likely to drive chronic autoimmune reactions than any other virus or vaccine. Also, the mRNA vaccine is using a single protein instead of many proteins, as would be the case for an attenuated viral vaccine which has been used in the past.
It’s just a single mRNA, so that is not a concern. Besides, even if that was the case, mRNAs and proteins are virtually always unstable, as others have pointed out.
In principle, it is safer than all other vaccine types. It is an acceptable risk because the risk from SARS-CoV-2 is not an acceptable risk.
For me, feeling bad for a day is a feature, not a bug. I’d much rather have the dose titrated to give some feedback that there is a significant immune response.
@cdods, are you aware that most of most viral diseases are your reaction to the virus, not the direct effects of viral replication?
But in principle, most of the adverse reactions associated with other vaccines should not happen with mRNA vaccines.
I’m not aware of much when it comes to biology. So realistically, I probably don’t have enough knowledge even ask more intelligent questions. I appreciate the answers, but I think this is an area where I just have to trust the experts.
As plenty of other people have said, the long-term risks are extremely low - lower than other types of vaccines. Plus the much lower relative risk compared to infection.
I’ll offer an additional perspective: I am in the Pfizer trial and received the actual vaccine. The side effects were not bad - about 24 hours of being achey starting about 12 hours after the 2nd shot, and, very briefly, a mild fever, also about 12 hours after the 2nd shot. Got it on a Monday, so the Tuesday was a bit uncomfortable, and woke up feeling fine on the Wednesday. And given the efficacy that we’ve seen, I’m now covered for however long the efficacy lasts. A day of not feeling great seems like a small price to pay. I know other people in the trial who also received the vaccine but had very mild or basically no side effects, so YMMV.