covid

covid-19 vaccine safety

First, an introduction

Throughout the COVID-19 pandemic I have been a fervent observer of health policies in Minnesota – primarily obtaining my information from the Minnesota Department of Health via their most-weekdays 2pm calls. I have done my best to follow their guidances and would say I am at ~92% compliance of the state’s guidelines/executive orders on gatherings, masking, etc since March. I don’t say this to brag, boast, or condemn – I only say it so you have an idea of where I personally stand on the pandemic. I fully believe COVID is real, that masks are crucial to stopping spread, and that public health officials in Minnesota are doing their best to keep us safe. I trust science, I get the flu shot every year, and in general I strongly believe everyone should get the “standard” vaccines. These are some of my biases.

However, upon first deciding to dive into research on the new SARS-CoV-2 (COVID-19) vaccines from Pfizer and Moderna I knew in order for this to be valuable I needed a specific mindset going into it. I knew if I went into doing this research with the belief that everyone should blindly get these vaccines then I would only try to find sources that prove that point of view. I specifically started this with the mindset that there was a very real possibility I would finish with the conclusion that the vaccine is not currently safe or advisable for people to get right now.

My target audience for this has been people who are reasonable, skeptical but hopeful, and open to science and reason. If you are someone who thinks all vaccines are dangerous or believes the many conspiracy theories around them – I invite you to keep reading but I doubt I will have much you cannot simply explain away through disbelief.

The following is primarily a synthesis of sources gathered from scholarly articles, the FDA/CDC websites, and occasionally news articles that are fact-based and not opinion-based. I strongly encourage you to go read the primary sources if you find yourself skeptical of anything I write here. My focus is presenting fact-based information regarding COVID-19 vaccine safety.

NOTE – At the point in which I am writing this, only the Pfizer and Moderna COVID-19 vaccines have received Emergency Use Authorization from the FDA. Therefore all references to COVID-19 vaccines going forward will be referring to those two in particular.

New vaccine approval process 1

We will begin this discussion by looking at the process to go from someone deciding “I should create a vaccine for X” to a syringe with said vaccine being pressed against your arm.

  1. Research & Development
    • Ah, good ol’ R&D. First, scientists come up with a rationale for a vaccine and then they conduct lab research for a vaccine candidate. Occasionally they will use animals to test. Once they have a scientific finding that would make such a vaccine practical, they are able to move to step 2.
  2. Pre-Clinical
    • Shockingly (or maybe not so shocking), step 2 is not “PUT IT IN EVERYONE’S ARM.” At this point a company or researcher must perform additional laboratory research and testing in animals to obtain information on how their vaccine candidate works and if it is likely to be safe in humans. Once they are ready to begin studies in humans, they compile all their research up to this point and submit it to the FDA with an Investigational New Drug application.
  3. Phase 1
    • This is the beginning of human testing. Typically this will only include about 20-100 volunteers who haven’t been exposed to the disease in question and are generally healthy. The purpose of this phase is to determine any adverse reactions and, if possible, get any early information on how effective it is on inducing an immune response.
  4. Phase 2
    • We now enter phase 2 of human testing, ONLY IF there are no safety concerns in phase 1. In this phase the number of participants increases to hundreds of people with varying health statuses from multiple demographic groups. Phase 2 testing will give more information on any potential adverse side effects as well as examining the relationship between the amount of vaccine given and the immune response from that dose. This testing is where the dosage amount is determined. There can also be a control group where vaccine recipients can be compared against people who have received a placebo.
  5. Phase 3
    • This is the one that you’ve probably heard the most about in the news because this is the last huge step before a vaccine can be approved. This is when the vaccine is administered to thousands of people, ranging anywhere from a couple thousand to one I found that had around 80,000 participants. The COVID-19 vaccines have each had around 35,000 participants for phase 3 (~50% of which received the vaccine). This phase continues to look closely at immune response in recipients as well as any potential safety concerns. There is also a control group which is given a placebo to allow researchers to compare the two groups for effectiveness of the vaccine. The number of cases of disease in the vaccinated group is compared to the number in the control group to see whether the vaccine reduces the incidence of disease. This phase will provide more information about less-common side effects.
  6. Special Considerations (Emergency Use Authorization) 2
    • At this point, in a relaxed and chill world we would go directly to step 7 and not need to pause here at step 6. However, there have been points in history where special considerations need to be given to vaccines that have an urgent need. For things like pandemics the development process can be expedited if there is need. The US government will bring together varying groups like government agencies, academia, international counterparts, nonprofits, and pharmaceutical companies to develop a coordinated strategy for prioritizing and speeding up development of the most promising vaccines. Sometimes the government may take on financial risk for pharmaceutical companies allowing them to invest aggressively on development without having to weigh costs to benefits. This can also allow them to distribute a potential vaccine much faster.
    • Early in a public health crisis like COVID-19 the FDA provides very clear and specific information to the pharmaceutical industry letting them know what scientific data and information is needed for a safe and effective vaccine. The FDA works especially quickly in these situations to provide advice on the proposed development plans and assessment of the data gathered.
    • Emergency Use Authorization is only granted if there are no fully approved alternatives.
  7. Seeking Approval – Biologics License Application Submitted
    • Even if a vaccine gets a special consideration like an Emergency Use Authorization will still go through this final formal approval step – it will just be after inoculations have been started.
  8. Phase 4 – Post Approval
    • The idea here is mainly that as a fully approved vaccine is being administered, all instances of side effects/adverse reactions/etc are all logged. This is essentially continued FDA oversight even after a vaccine is approved.

Messenger-RNA (mRNA)

Alright so this is a pretty big topic and many books and papers have been written on mRNA – I’m going to keep this fairly high level. If you are super interested, I strongly recommend you dive into this further :).

You’ve heard of DNA, maybe from Jurassic Park or maybe from 7th grade science class. DNA is an acronym for deoxyribonucleic acid which is a mouthful, so we just call it DNA. RNA is Ribonucleic acid, similarly – a mouthful. DNA replicates and stores genetic information and is a blueprint for all genetic information contained within an organism. 3 This differs from RNA because RNA converts that genetic information contained within DNA to a format that is used to build proteins and then moves it to protein factories.

Here’s a fun analogy 4. Pretend your body is a big technology company that is going to produce the brand new Galaxy iPhone S Max 15. The technical schematics for how to build the new phone is like the DNA in your body. It tells people building the phones exactly how to do it and what parts to use. The RNA is the person who takes those schematics and distributes them to the factories where the phone is going to be produced. When that person arrives at the factories they not only program the machines to be able to manufacture the phones, that person also turns on those machines and begins the process. 5

Within the world of RNA, there are three types. Transfer RNA (tRNA), Ribosomal RNA (rRNA), and of course our dear friend Messenger RNA (mRNA). Messenger RNA copies portions of the genetic code and transports those copies to the cellular factories (ribosomes) that produce proteins from that code. tRNA is what brings amino acids, the basic protein building blocks, to the protein factories. rRNA is part of the factory itself.

So essentially:

  • DNA replicates and stores genetic information.
  • RNA converts that information to a format that is used to build proteins and send it to protein factories.
  • mRNA is one of three subtypes of RNA. mRNA is the one that copies and transports portions of genetic code to cellular factories.
  • tRNA supplies the building blocks.
  • rRNA is part of the factory itself.

At this point you know all the detail you need in order to understand how the COVID-19 vaccines work. Onwards!

How it works | COVID-19 Vaccines

So-called “normal” vaccines work by injecting a weakened or inactivated germ into your body – this allows your body to trigger an immune response and “learn” how to fight that specific type of germ without being at risk of losing the fight. However, mRNA vaccines work quite differently. “Instead, they teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies. That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies.” 6

At this point I’d like to send you to a wonderful New York Times article that goes through how the COVID-19 vaccines work. I will give my brief summary below but that article goes through step-by-step how the vaccine works with images that really help to understand how it works.

I couldn’t point you to a secondary source of such high importance without briefly talking about the credibility of the author. Carl Zimmer has written for The New York Times (obviously), Discover, and National Geographic. He is a fellow at Yale University, and an adjunct professor of Molecular biophysics and biochemistry at Yale as well. He has written over 13 books on a variety of science topics and has received numerous awards including the National Academies Communication Award from the US National Academy of Sciences.7

https://www.nytimes.com/interactive/2020/health/pfizer-biontech-covid-19-vaccine.html

Go to that article and scroll through, I’ll wait.

Here is my brief summary of that article (but go read it, person-who-skipped-reading-it) occasionally using their words mixed with some of my own.

On the surface of the COVID-19 virus are a bunch of proteins that you can visualize in your brain as a bunch of spikes protruding from the virus. Imagine each virus’ spike as a unique shape that identifies what type the virus is. For example the COVID-19 virus’ spike proteins might look like a bunch of triangles, whereas the spike proteins for the flu could look like pointy sticks. The essential thing is that we need our body to know how to look for the unique shape of COVID-19’s spike proteins and to destroy those cells if it finds any. Naturally, this could happen by being infected by COVID-19, our body sees what the virus’ spike proteins look like, and sends antibodies to kill anything that looks like that in the future.

However, we don’t want to get infected by COVID-19 – that’s the whole point. So instead, very smart people are using Messenger RNA in the vaccine. Essentially, when they inject the vaccine into your arm you can imagine many tiny tiny tiny pieces of mRNA encased in little circles of fats (the fats just protect the mRNA) are put into your body. Those little fat balls (haha) of mRNA will bump into other cells in your body and release the mRNA into into the cell. The mRNA contains instructions on how to build spike proteins that are shaped exactly like the ones that are on COVID-19 virus cells. This is how we can introduce what the virus spike proteins look like without ever putting COVID-19 into your body. What happens to that mRNA in your body? It is broken down by the cells rapidly after attaching to them.

Many people get concerned seeing the symptoms others experience within a day or two of getting a vaccine – thinking that these are symptoms of the actual virus itself. Any symptoms you experience are from your body producing antibodies to learn how to fight the virus. Just to reiterate – especially with mRNA vaccines there is never any COVID-19 virus entering into your body.

Can we pause for a moment to think about how incredible of a concept this is? mRNA technology basically allows us to take the same vaccine composition and just change the instructions in the mRNA molecules to be able to vaccinate against other viruses without starting from scratch. Incredible.

Addressing specific concerns

One of the large motivations I had to research these vaccines and the safety of them is seeing many concerns from friends and family on social media and in conversations. In this section I’m going to address various concerns one-by-one and let you know what I was able to find. With any of these – please consult with your primary care physician if you have any specific concerns. I may address further concerns as time goes on.

Infertility/Pregnancy

The American Academy of Family Physicians states that “the mRNA is rapidly broken down by the cell once the instructions have been transmitted, so it does not cause mutations or cellular defects, and has not been associated with infertility.” 8 The American Society for Reproductive Medicine published recommendations for the reproductive care community that stated nearly the same thing – “[We do] not recommend withholding the vaccine from patients who are planning to conceive, who are currently pregnant, or who are lactating” and “Patients undergoing fertility treatment and pregnant patients should be encouraged to receive vaccination based on eligibility criteria.” 9

It was rushed

It had a short timeline and was developed quickly, but it was not rushed. I cannot give you a direct quote here, but on a MN Department of Health (MDH) call recently (perhaps mid November) the Commissioner of MDH, Jan Malcolm, gave three reasons as to why we were able to develop/produce this vaccine so quickly:

  1. Typically during vaccine trials they would go very sequentially, recruit for phase 1, execute for phase 1, recruit for phase 2….etc. To expedite the process for this one they started recruiting for phase 2/3 testing before phase 1 was complete.
  2. In normal circumstances a pharmaceutical company creating a vaccine would avoid producing much of the vaccine until it received final FDA approval. At that point the company would begin mass production and distribution. However, due to the public health crisis the US government took on the financial risk of creating the vaccines prior to approval (even Emergency Use Authorization) and if the Phase 2 or Phase 3 studies proved the vaccine to be dangerous or ineffective the already produced vaccines would have been destroyed. This allowed us to have millions of doses of vaccine already created at the time the Emergency Use Authorization was granted.
  3. The FDA is a large government agency. Large government agencies (and just medium/large companies in general) do not move with quickness or agility mostly due to drawn out processes, red tape, and bureaucracy. Due to the urgency of the pandemic, the FDA worked much closer and more directly with the companies working on these vaccines. There were significantly faster feedback loops than there might be in a normal scenario.

I will humbly add a 4th reason to Director Malcolm’s list above. mRNA vaccines have never been approved in the past but they have been studied for decades. Researchers have been studying mRNA use in vaccines for things like flu, Zika, rabies, and cytomegalovirus 10. Like I said earlier, once you’ve created the process for creating an mRNA vaccines – the biggest difference is just changing the set of instructions inside the mRNA itself. Pfizer had two versions of the vaccine created and ready to begin phase 1 testing by May, only 4 months after the COVID-19 virus’s genetic sequence was released by China.

Trump pressured the FDA

There was a report picked up by multiple news sources saying that on December 11th, “White House Chief of Staff Mark Meadows on Friday told FDA commissioner Stephen Hahn to be prepared to submit his resignation if the agency did not clear the vaccine by day’s end” 11 If you remember, the Pfizer vaccine was granted Emergency Use Authorization on December 11th, the same day that alleged threat was made. HOWEVER, the FDA was planning on giving the EUA the following morning regardless. Whether the White House was successful in pressuring the FDA to give EUA 12 hours early or not, the practical difference is meaningless. Unfortunately, I’m in agreement with this Op-Ed article from the Washington Post where the author says “The costs, meanwhile, are potentially hefty, because the very act of issuing the order signals that politicians are overriding the FDA’s experts. The last thing we need now is for people to believe this was a political rather than a technical decision.” 12 It is worth knowing that before the FDA approves a vaccine for EUA, an independent group named the Vaccines and Related Biological Products Advisory Committee (VRBPAC) meets to decide whether to recommend the vaccine for approval. The live conference call where VRBPAC discussed approving the Pfizer and Moderna vaccines in December are both available on Youtube if you’re curious to hear their discussions. 13 14 The current list of members of VRBPAC is available online and includes 22 experts from all over the country (CT, MD, OH, GA, MA, WA, TX, PA, IL, DC) and all of their CVs (fancy resumes) are available on the FDA website. 15 This diverse committee voted to approve Pfizer’s vaccine (17 yes/4 no) 16 and Moderna’s vaccine (20 yes/0 no). 17 Personally, this information gives me confidence that Trump’s pressure, even if it was successful in influencing the final decision of approval, does not change that the VRBPAC group overwhelmingly voted in approval of both vaccines.

Long term side effects

So far, there are no indications that would lead medical professionals to believe either COVID-19 vaccine will cause long term health side effects. Is it hypothetically possible? Sure it is, because it is a problem of infinite time scale. What if taking a Tylenol could cause you to develop dementia 70 years after taking it? We still wouldn’t know because it only started being sold 55 years ago. However, I guarantee you’ve never considered that risk when taking a couple to get rid of a bad headache. I bring up this (slightly ridiculous) hypothetical because I would argue that the entire drug/prescription/vaccine world is centered around the idea of trade-offs and risk/reward analysis.

Medical researchers do as much testing and trials as reasonably possible to make a determination if the benefits that a drug brings a person outweighs the rare chance it could cause a negative side-effect in the short-term or, yes, long-term. People who were in Pfizer’s phase 1 trials have now had the vaccine in them for 7 months and no longer term health concerns have been noted. There is still a risk/reward analysis to be done here though – the vaccine protects you from COVID-19 but theoretically could have some long-term risk to a subset of people. That is a theoretical risk. If you get COVID-19 it is possible you will have mild symptoms in the short-term but those mild (or more severe) symptoms could continue much longer. Some common COVID-19 symptoms of those who have had weeks or months of symptoms include coughing, ongoing (sometime debilitating) fatigue, body aches, shortness of breath, loss of taste and smell, headaches, brain fog, and others. 18

Researchers estimate about 10% of COVID-19 patients have medium to long term side effects. At this point we have no idea how long these symptoms could last because we only have a year of data on COVID-19. A member of my family has personally experienced brain fog and the loss of taste for at least a few months now after having a mild COVID-19 infection. Personally, I believe the risks associated with getting the COVID-19 virus are much higher and more evidence based than the theoretical risks of getting the vaccines for it.

Vaccine was not tested on children

The Pfizer vaccine was only tested on and approved for people ages 16 and above and the Moderna vaccine is for people 18 and older. 19

Cost

Free! At least for now. Everything I have found is that the government will be covering the cost of the vaccine at least through 2021, but most likely longer. Healthcare providers are able to bill your insurance company a nominal fee for the cost of administering the vaccine, but the vaccine itself is free. It is expected that your health insurance will completely cover that fee and there are funds set up to cover that cost for uninsured people as well. You should fully expect to pay $0 out of pocket for the vaccine. 20

Conclusion

I was expecting to have a longer conclusion here, however I think I already stated my main conclusion in a previous section.

Personally, I believe the risks associated with getting the COVID-19 virus are much higher and more evidence-based than the theoretical risks of getting one of the vaccines for it.

If I was given the opportunity to get the Pfizer or Moderna vaccines today, I would absolutely take it and do so confidently. More importantly, I would recommend my loved ones do the same. (UPDATE: I have received both doses of the Pfizer vaccine and did so without hesitation.)

Again, I am not a doctor and I am not a medical expert. Always feel free to defer to the much smarter people in the resources scattered throughout this post as well as some specific additional ones I’ll be linking below.

Further Resources

I have linked to multiple resources throughout this post but I would like to list a handful of interesting sources below (possibly already cited elsewhere) as well as why I find them interesting. It’s possible more will be added here as time goes on.

 

New York Times – How the Pfizer-BioNTech Vaccine Works

If you skipped this article above, I don’t blame you. However, I strongly recommend you go read through this. It gives a great illustrated explanation of how an mRNA vaccine works as well as a timeline of the development of the Pfizer vaccine.

 

New England Journal of Medicine – Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine

This is the medical journal article that fully discusses the process of Pfizer’s Phase 3 trials including the demographics of participants, the methods of conducting the study, along with detailed results including symptoms experienced and conclusions. Highly worth a read if you can avoid getting intimidated with fancy words that probably don’t need to be fully understood ;).

 

Moderna – Article Discussing Phase 3 Study

I was unable to find a full medical journal article detailing Moderna’s phase 3 clinical trials – it is possible it hasn’t been released yet. However, this at least gives a high level overview of the details and results/conclusions of their phase 3 trial.

 

FDA Fact Sheet for Recipients of the Pfizer COVID-19 Vaccine

From what I can tell, this is the fact sheet that recipients of the Pfizer COVID-19 vaccine should be given just before receiving the vaccine. You could read through this ahead of time to be more informed and be able to ask specific questions to the pharmacist administering the vaccine or your primary care physician.

 

Moderna VRBPAC Meeting Overview

This is dense and long, but shorter than watching the 8 hour meeting the VRBPAC group had to discuss whether or not to recommend the Moderna vaccine for EUA.

 

EUA Approval from FDA for Pfizer Vaccine

This is the official approval from the FDA and lays out the restrictions and guidelines of that authorization. Confirms the ingredient list of the vaccine.

 

Final Thoughts

As I said before, I’m not an expert on any of this. I simply wanted to present this sometimes complex information in a way that I think makes more sense and is fairly concise for the people that don’t have time to do the research themselves. If you are an epidemiologist, immunologist, or anyone else who is much more qualified than myself – please feel free to reach out if you find any inaccuracies above that hurts my overall message. I am open to feedback and will make revisions if needed.

 

Revision History

If I make any changes to this post I will write a brief summary of those changes below for full transparency.

2020-12-28 – Initial posting

2021-04-26 – Updated informing I have received both doses of the Pfizer vaccine

 

Citations:

  1. Most of the information from this section comes from the following page on FDA’s website – FDA Vaccine Development Overview
  2. This article from the FDA gives some great information that dives into the Emergency Use Authorization. It talks specifically about EUA in relation to the COVID-19 vaccines. https://www.fda.gov/vaccines-blood-biologics/vaccines/emergency-use-authorization-vaccines-explained
  3. Key Differences of DNA and RNA
  4. At least, I think it’s fun!
  5. Alright, I’m starting to think there are better analogies out there but I refuse to search for one because then I’ll realize there was a much simpler option available. Hopefully this made sense.
  6. Understanding mRNA COVID-19 Vaccines – FDA
  7. https://en.wikipedia.org/wiki/Carl_Zimmer
  8. https://www.aafp.org/dam/AAFP/documents/patient_care/public_health/COVID19-Vaccine-FAQs.pdf
  9. https://www.asrm.org/globalassets/asrm/asrm-content/news-and-publications/COVID-19/COVIDtaskforceupdate11.pdf
  10. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html
  11. Washington Post – https://www.washingtonpost.com/health/2020/12/11/trump-stephen-hahn-fda-COVID-vaccine/
  12. Washington Post – https://www.washingtonpost.com/opinions/2020/12/11/trump-fda-rushing-COVID-vaccine-trust/
  13. VRBPAC Meeting 12/10/2020 for consideration of Pfizer recommendation – https://www.youtube.com/watch?v=owveMJBTc2I&feature=youtu.be
  14. VRBPAC Meeting 12/17/2020 for consideration of Moderna recommendation – https://www.youtube.com/watch?v=I4psAfbUtC0&feature=youtu.be
  15. List of VRBPAC Members, names are links to their CVs – https://www.fda.gov/advisory-committees/vaccines-and-related-biological-products-advisory-committee/roster-vaccines-and-related-biological-products-advisory-committee
  16. Pfizer Vaccine VRBPAC Vote Results – https://www.businesswire.com/news/home/20201210006182/en/
  17. Moderna Vaccine VRBPAC Vote Results – https://investors.modernatx.com/news-releases/news-release-details/moderna-receives-fda-advisory-committee-vote-supporting
  18. UC David Health Article on COVID-19 “Long Haulers” – https://health.ucdavis.edu/coronavirus/COVID-19-information/COVID-19-long-haulers.html
  19. Mayo Clinic article discussing FAQs of the COVID-19 vaccines – https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-vaccine/art-20484859
  20. Centers for Medicare & Medicaid Services press release about this topic – https://www.cms.gov/newsroom/press-releases/trump-administration-acts-ensure-coverage-life-saving-COVID-19-vaccines-therapeutics