By Dr. Dhia
Aldoori March/2021
(Orange
font text targets other caregivers or indicates that that text is my conclusion.)
When the vaccines looked like they were going to hit the
stage somewhere in December 2020, I started looking for the data related to its
testing. I was looking at efficacy, safety, how many people were vaccinated,
how many controls (individuals given sham vaccinations to compare) were
employed, mechanism of action, etc.
The numbers we were hearing were the stellar efficacy of 95%
and 94.5% for the Pfizer/BioNtek and Moderna vaccines, respectively.
Starting with ingredients:
The Pfizer-BioNTech COVID-19
Vaccine includes the following ingredients: mRNA (messenger ribonucleic acid),
lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2
[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide,
1,2-Distearoyl-sn-glycero-3- phosphocholine, and cholesterol), potassium
chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium
phosphate dihydrate, and sucrose.[1]
The Moderna COVID-19 Vaccine
contains the following ingredients: messenger ribonucleic acid (mRNA), lipids
(SM-102, polyethylene glycol [PEG] 2000 dimyristoyl glycerol [DMG],
cholesterol, and 1,2-distearoyl-sn-glycero-3-phosphocholine [DSPC]),
tromethamine, tromethamine hydrochloride, acetic acid, sodium acetate, and
sucrose.[2]
Both Pfizer/BioNtech and Moderna vaccines do NOT contain
live virus and therefore can NOT cause infection in recipients. They also do
NOT interact with our own DNA in any way, but rather use mRNA (messenger
ribonucleic acid). How it
works: the ‘instructions’ (mRNA) enter immune cells, who ‘listen’ to the
instructions and make the spike protein piece. After the protein piece is made,
the cell breaks down the instructions and gets rid of them. Next, the cell
displays the protein (spike) piece on its surface which trigger an immune
response with cytokines and ultimate antibody production which can defend
against severe disease caused by SARS-CoV-2. (I do not know yet to what extent it prevents against
actual infection – science pending).
The next thing here I want to look at is, what do they mean
by ‘efficacy’?
The Moderna vaccine phase 3 trial had 30,351 participants.
The primary efficacy end point relied on manifestation of symptoms suggestive
of COVID-19 with a positive SARS-CoV-2 by RT-PCR. In those aged 65 and older
the efficacy was 100% (meaning no symptoms), and in ages 18 to under 65 the
efficacy was 93.4% with an overall participant average efficacy of 94.5%. None vaccinated
had severe illness or were admitted to a hospital. [3]
The Pfizer/BioNtech vaccine phase 3 trial had 44,000+ participants. Here also the primary efficacy end point relied on manifestation of symptoms suggestive of COVID-19 with a positive SARS-CoV-2 by RT-PCR or in some cases a local nucleic acid amplification test (NAAT) result. There was 1 severe COVID-19 occurrence from 14 days after Dose 2 out of 18,175 vaccinated. In the placebo group of 18,261 there were 3 severe cases.[4] (I thought there would be more in the placebo group.) The other efficacy endpoint I looked at was based on the first COVID-19 occurrence based on CDC defined symptoms from 7 days after dose 2. See table 22 in reference [4]. The number of vaccinated participants was 19,965 and the placebo group was 20,172. The number of cases in the vaccinated group was 9, and the number of cases in the placebo group was 172 ending with a vaccine efficacy of 94.7%. (I am assuming the different numbers of vaccinated and placebo seen, results from the different times at which data was extracted for analysis, or because of their status regarding whether or not they were infected previously. I could not tell which.)
Given that both methods relied on reporting symptoms, I surmise
an unknown number of participants must have gotten COVID-19 without being detected,
as they were symptom free subjectively. (I wish all the participants would have had periodic, e.g. weekly testing
for the virus, which would have given us more accurate numbers overall.)
The safety issues: (I have relied on the CDC - Centers for Disease Control - which I do trust
at this time for safety information.) COVID-19 vaccines appear
relatively safe to date (March 28, 2021) after millions of people in the United
States have received COVID-19 vaccines, and these vaccines will continue to undergo
safety monitoring. Some people have no side effects. Others have reported
common side effects after COVID-19 vaccination like swelling, redness and pain
at injection site, fever, headache, tiredness, muscle pain, chills, and nausea.
A small number of people have had a severe allergic reaction (called
“anaphylaxis”) after vaccination, but this is extremely rare.[5]
That said, the word ‘rare’ takes on a different meaning when you know that the
actual reports of death through March 22, 2021 have been 2,216. That’s a very
unfortunate loss of life representing 0.0018% of 126 million doses of COVID-19
vaccines administered in the United States from December 14, 2020.[6]
So I recommend getting the vaccine in a venue that has the capacity to deal
with a possible severe allergic reaction. Also stay for 15–30 minutes after
your injection for observation, which becomes even more important if you are an
allergy prone person.
The third vaccine I would like to talk about is the vaccine from
Janssen Biotech, Inc. (a pharmaceutical company of Johnson & Johnson). The
related Emergency Use Authorization (EUA) application is dated February 26,
2021 and since has been granted by the Food and Drug Administration (FDA). This vaccine is administered in 1 shot with
similar side effects to the two dose vaccines (Pfizer/BioNtech, Moderna).
The Janssen COVID-19 Vaccine includes the following
ingredients: recombinant, replication-incompetent (i.e. can NOT
cause infections) adenovirus type 26 expressing the SARS-CoV-2 spike protein,
citric acid monohydrate, trisodium citrate dihydrate, ethanol,
2-hydroxypropyl-β-cyclodextrin (HBCD), polysorbate-80, sodium chloride.[7]
How it
works: after administration of Ad26.COV2.S, binding of the Ad26 vector to
cellular receptors is mediated by fibers on the Ad26 capsid. After transduction
of the cell, episomal vector DNA drives cellular production of the transgene
encoded S protein. The S protein is then expressed on the cell membrane where
it is sensed by the host immune system, resulting in humoral and cellular
immune responses directed against the SARS-CoV-2 S protein.[8]
The J&J/Janssen vaccine was 66.3% effective in clinical
trials (efficacy) at preventing laboratory-confirmed COVID-19 illness in people
who had no evidence of prior infection 2 weeks after receiving the vaccine. The
vaccine had high efficacy at preventing hospitalization and death in people who
did get sick. No one who got COVID-19 at least 4 weeks after receiving
the J&J/Janssen vaccine had to be hospitalized.[9]
The efficacy numbers will change as more people are vaccinated.
So, what is the actual benefit from these vaccines? They help
prevent serious illness and death from SARS-CoV-2. Also, of vital import is it will
help end the pandemic by increasing herd immunity (assuming enough individuals get it) and by
virtue of lessening manifestations of COVID-19 which spread the virus such as
coughing and resultant aerosolization of virus particles.
To get or not to get: GET. The risk/benefit ratio is very
convincing to me in favor of getting one of the vaccines above. I personally received my first Moderna
shot December 29, 2020 and the second one January 26, 2021. (The second shot
laid me out in bed the next day with significant achiness, headache, and chills
– so allegedly my immune
system is still intact J.)
Bibliography
[1] Pfizer, “PFIZER-BIONTECH COVID-19
VACCINE.” https://www.fda.gov/media/144414/download (accessed Mar. 29, 2021).
[2] Moderna TX and Inc, “FACT SHEET FOR RECIPIENTS AND CAREGIVERS
EMERGENCY USE AUTHORIZATION (EUA) OF.” Accessed: Mar. 29, 2021. [Online].
Available: www.modernatx.com/covid19vaccine-eua.
[3] FDA and Cber, “Vaccines and Related Biological Products
Advisory Committee December 17, 2020 Meeting Briefing Document - FDA,” 2020.
[4] Pfizer, “Vaccines and Related Biological Products Advisory
Committee December 10, 2020 Meeting Briefing Document- Sponsor,” 2020.
[5] CDC, “Safety of COVID-19 Vaccines | CDC.”
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html
(accessed Mar. 28, 2021).
[6] CDC, “Selected Adverse Events Reported after COVID-19
Vaccination | CDC.”
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html
(accessed Mar. 28, 2021).
[7] D. Administration, “FACT SHEET FOR RECIPIENTS AND CAREGIVERS
EMERGENCY USE AUTHORIZATION (EUA) OF.” Accessed: Mar. 29, 2021. [Online].
Available: www.janssencovid19vaccine.com.
[8] JANSSEN BIOTECH, “Vaccines and Related Biological Products
Advisory Committee February 26, 2021 Meeting Briefing Document- Sponsor,” 2021.
Accessed: Mar. 29, 2021. [Online]. Available:
https://www.fda.gov/media/146219/download.
[9] “Information About Johnson & Johnson’s Janssen COVID-19
Vaccine | CDC.”
https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/janssen.html
(accessed Mar. 29, 2021).
