Please listen to our two part podcast on the Pfizer COVID 19 vaccine.

If you would like to get more of our podcasts on your RSS feed, type in “DownEast Emergency Medicine” or visit our Podbean Site.

What is the mRNA COVID-19 vaccine?

Disclaimer: I am not an infectious disease physician, immunologist, or population health specialist. These perspectives are those of an Emergency Medicine physician. In order to expedite the delivery of this material to you, the frontline provider, this content did not undergo our typical peer review process.

What is an mRNA vaccine?

source: https://commons.wikimedia.org/wiki/File:DNA_to_protein_or_ncRNA.svg

mRNA vaccines use, you guessed it, RNA rather than proteins. In general, vaccines we have received in the past inject some protein from the pathogen (here we are taking about viral pathogens but bacteria, fungi, parasites, and viruses are the most common pathogens) into our body, usually our muscle. Our body’s immune system sees the foreign protein and mounts an immune response to it.

Rather than inject a protein into our body, mRNA vaccines inject the mRNA that codes for the protein. The mRNA then goes into our cells and ribosomes where the mRNA is used to make a protein (in the case of the COVID-19 vaccines the “S” or “Spike protein”). The protein then gets excreted from the cell and our immune system does the same process of recognizing the protein as foreign, mounting an immune response.

While this is different (and a bit strange to use some of our own body’s mechanics to make the protein) it is interesting to recognize that when we are infected with a virus, including the common cold, these viruses use the same process to make a foreign protein.

Are there any other mRNA vaccines?

Yes. The idea for mRNA vaccines has been around for over 10 years. In fact, in 2017 some phase 1 study data on a Rabies mRNA vaccine was published [1]. There are not, however, mRNA vaccines in widespread use. Why is that? It is likely because mRNA is pretty fragile. It breaks down easily and therefore is not ideal for use in the many of the places where vaccines are most beneficial - rural or third world situations where disease burdens are high. With the subzero temperature storage needs of these vaccines, their distribution and use in such environments is technically challenging.

https-//www.sandiegouniontribune.com/news/science/story/2020-06-06/race-for-vaccine accessed Deb 8 2020

Pfizer phase 3 [2]

The data and graphics presented below are from the publicly available full text article. They are reproduced here to help facilitate understanding of the results. Please reference the full article for complete details.

Intervention: Vaccine (30 micrograms per dose, two doses 21 days apart)

Control: Placebo

Inclusion: Patients who were 16 years or older and either healthy or had stable chronic medical conditions

Exclusion: <16 years old, medical history of COVID-19, treatment with immunosuppressives, diagnosed with an immunocompromising condition

Outcome Measures:

Safety*
- 37,706 patients
- Solicited specific local and systemic adverse events and/or use of antipyretic or pain medication up to seven days after each dose (8183 patients)
- Prompted and unprompted reports of reactogenicity events up to one month after receipt
- Unsolicited serious events up to six months after the second dose
  - *excluding HIV patient data

Efficacy*
- 36,523 patients
- COVID infection rate at least seven days from the second dose of vaccination/placebo
- COVID infection rate in those with and without evidence of prior infection
- Severe infection rate at least seven days from the second dose of vaccination/placebo
  - *actually, included 100 participants age 12-15

Results:

Safety- remember this data is from the “reactogenicity” subset of 8183 patients.
- Local reactions
  - The vast majority (83% in 16-55 age group, 71% in >55 age group) experienced pain at the injection site with the first dose. Most of these were rated as mild. Rates were lower with the second administration.
  - See Figure 1
- Systemic Reactions
  - Reactions or “systemic effects” were common and more common after the second dose. They were also more common in the 16-55 age group, likely related to a more robust immune system.
  - In order of probability in the 16-55 age group they were fatigue (59%), headache (52%), muscle pain (37%), chills (35%), joint pain (22%), fever (16%). See Figure 2 below for full details.
  - Severe reactions were uncommon. After the first administration, severe events were seen in 0.9% of those getting the vaccine. In round 2, they were seen in <2%, except for fatigue which was noted in 3.8% of subjects and headache seen in 2%.
  - It is worth noting that 16% of younger respondents reported a fever after the second dose of the vaccine, as did 11% of older subjects. This could come in to play if your work has a health screen with questions regarding symptoms.

Fig1. local reaction rates. source: https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

fig 2. systemic reaction rates. source: https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

Efficacy
- The vaccine had 95% efficacy after two 30 microgram doses 21 days apart. Below graphic (Figure 3) shows rates of COVID-19 infection from first, initial injection.
- COVID19 OCCURANCE >7 DAYS FROM 2ND DOSE IN THOSE WITHOUT PRIOR INFECTION:
  - Vaccine: 8 (N=18,198)
  - Placebo: 162 (N=18,325)
- COVID19 OCCURANCE >7 DAYS FROM 2ND DOSE IN THOSE WITH OR WITHOUT PRIOR INFECTION:
  - Vaccine: 9 (N=19,965)
  - Placebo: 169 (N=20,172)

fig 3. efficacy data. Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2034577

Operation Warp Speed

The last series of questions one may ask (I know I did) is“was this vaccine rushed?” with the obvious follow up question, “if it was rushed, are there any safety concerns the above data may not address?”

To answer these questions in order— Yes, the vaccine was most definitely rushed out. As we seen in the graphic below a vaccine normally takes ~6 years to come to market or mass administration. This one was done in little over a year.

So if the vaccine was rushed, does that mean it was made sloppily? Were normal steps skipped or avoided? The answer to this question, in my mind, is no. The Operation Warp Speed graphic below (figure 4) shows how all of the key steps to a vaccine’s production were maintained. In order to expedite production, interestingly, they allowed these steps to happen simultaneously, rather than in series.

Figure 4 - source: https://www.defense.gov/Explore/Spotlight/Coronavirus/Operation-Warp-Speed accesssed Dec 11 2020

mRNA vaccines inject mRNA rather than protein into our bodies. Our cells take up the mRNA and our ribosomes make the protein. Our immune system then mounts a response to this protein. In the Pfizer COVID-19 vaccine this is the “S” or “Spike” protein.
mRNA vaccine technology has been around for over 10 years, but has had limited use, likely because of the fragility and transport issues.
The Pfizer phase 3 data shows it is effective (95% efficacy) and collectively safe, with some notable side effects or reactions:
- High rates of fatigue and headache.
- Modest rates of muscle pain, chills, joint pain and fever.
- Rare incidence of severe effects (3.8% had severe fatigue, 2% had severe headache).

Author’s Opinion:

I found the fact that the COVID-19 vaccine was going to be an mRNA vaccine a little unnerving at first. The idea of the vaccine particles entering into my cells and using my cellular architecture to make the protein felt a little “icky” (for lack of a better scientific term). Then, as I read and thought more on the topic, I realized this is what happens every winter when I get the common cold. Sure, it’s weird, but the fact that science has used this same process to actually help my body is a cool notion to me.

After reading the Pfizer data I was also put a little more at ease. To be clear, there are several, notable limitations to this study. First, it is an industry sponsored study. Second, we clearly don’t have long term outcome data yet. These are important caveats when making the personal decision to be vaccinated. But when you weigh the alternative of contracting COVID-19 (and more importantly spreading COVID-19), I think it is a relatively easy decision for me. I’ll schedule my vaccination for a time when I have a few days off to deal with the potential reactogenicity, take some ibuprofen, and not trigger my employee health screening. Afterword, I will go to work feeling safer and come home after my shift a little less worried about what I’m bringing with me.

References:

Alberer M, Gnad-Vogt U, Hong HS, Mehr KT, Backert L, Finak G, Gottardo R, Bica MA, Garofano A, Koch SD, Fotin-Mleczek M, Hoerr I, Clemens R, von Sonnenburg F. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet. 2017 Sep 23;390(10101):1511-1520. doi: 10.1016/S0140-6736(17)31665-3. Epub 2017 Jul 25. PMID: 28754494. [pubmed]
Walsh E. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 Oct 14. [NEJM]
Department of Defense. CORONAVIRUS: OPERATION WARP SPEED. https://www.defense.gov/Explore/Spotlight/Coronavirus/Operation-Warp-Speed/
San Diego Union Tribune. Scientists are struggling to quickly find a vaccine that can vanquish coronavirus. https://www.sandiegouniontribune.com/news/science/story/2020-06-06/race-for-vaccine