It’s been a tragic week with increasing numbers of hospitalizations and deaths, but there is a glimpse of some hopeful change. This week’s newsletter focuses on the Pfizer vaccine. As always, if you were forwarded this email, you may sign up to receive it weekly here.
Is The Pfizer Vaccine Safe?
The Pfizer vaccine received endorsement from an independent panel of scientists assembled by the FDA. After reviewing the data from the trial so far, including 44,000 people, the panel recommended moving forward with widespread use. This independent opinion is a big step in the process for FDA approval. A formal announcement from the FDA regarding its final decision on emergency approval is expected soon.
The independent panel voted 17-4 in favor of the vaccine with some questions that still remain unanswered.
- Do people who are vaccinated still transmit the virus? Although the data shows that the vaccine is more than 90% effective in preventing a person from becoming ill with COVID-19, there is not yet any data about the ability of a vaccinated person to transmit the virus. Asymptomatic transmission is thought to contribute greatly to the spread of COVID-19. Ongoing study of the trial participants is necessary to determine if they can still carry and transmit the virus. This means vaccinated people will still need to wear masks and comply with distancing and other measures.
- Is it safe in people under age 18? Some of the dissenting panel members questioned the need to include those age 16 and 17 given their small numbers in the study (283) and the small risk of COVID-19 complications in this age group.
- Should those who received a placebo be notified? In standard vaccine trials, participants are not told if they have received a placebo or the treatment drug, and monitoring is continued to determine the vaccine’s duration of effectiveness and long term side effects. However, in the setting of a global pandemic with a high likelihood of the placebo group becoming infected, should they be offered a vaccine? This is an important question because monitoring both groups for longer periods of time allows for long term side effects to be discovered. However, the ethical question regarding the trial participants remains. According to reports, Pfizer has proposed offering the vaccine first to the most at-risk (over age 70) participants who received the placebo, and delaying those at lower risk (younger and healthier volunteers)
- Does the vaccine work in children and pregnant women? These two groups were not included in the original study and are not part of the approval. Pfizer is beginning to study these populations but approval is not expected until next year.
- Is there any additional risk to those with a history of severe allergic reactions? The U.K approved the vaccine last week. Two people who received the vaccine this week had severe allergic reactions. Both had a reported history of prior allergic reactions requiring them to carry epi pens, but did not have a history of reactions to products in the vaccine. As a result, the U.K issued a warning asking that anyone with a history of severe allergic reactions (regardless of type) delay being vaccinated until further investigation can take place.
Prior to the independent panel meeting, the FDA released its own 53 page summary and included it in the meeting briefing documents. This represents a summary of their own review of the data, a step not required in other countries. The entire packet can be found here, and includes summary tables for the demographics of study participants.
The summary report includes a graph showing that even 1 dose of the vaccine is effective in reducing the risk of contracting COVID.
The divergent lines show the incidence of COVID-19 occurring in the two groups, placebo vs treatment group. With a single dose, the vaccine was seen to reduce the chances of contracting COVID-19 after approximately 10 days. However, no formal conclusion can be drawn about a single dose because most participants received the second dose after 3 weeks.
Side effects were heavily discussed in the report. When conducting an analysis on adverse events, the FDA looked at several factors:
- The total number of adverse effects.
- The number of adverse events in the treatment group vs the placebo group.
- The number of adverse events in the study compared to the general population.
This type of analysis allows for a determination to be made regarding the proposed cause. Study participants can still have other medical illnesses, like heart attacks and strokes, but these must be at the same rate in the general population otherwise they may represent adverse events caused by the vaccine. Here is what they found:
- 6 deaths occurred in participants. 2 in the treatment group and 4 in the placebo group. In the treatment group: one died from cardiac arrest 62 days after the second vaccine administration, and another 3 days after the first vaccine administration. In the placebo group: one cardiac arrest, one hemorrhagic stroke, and two unknown. All these were felt to reflect the same rate as the population in general and were not felt to be related to the study.
- 4 cases of Bells Palsy occurred in the treatment group and none in the placebo group. Although there were more cases in the treatment group, the number of cases matches what is expected in the general population, so the vaccine was not felt to be the cause. However, further monitoring was recommended.
- 12 cases of appendicitis occurred during the trial period, 8 in the treatment group and 4 in the placebo group. Although there were more in the treatment group, once again the rate was not higher than expected for the general population. There was no concern that these cases were related to the vaccine.
- There were numerous less severe symptoms reported in the vaccine group. According to the report “The most common solicited adverse reactions were injection site reactions (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%).” In addition, lymphadenopathy (swollen lymph nodes) was reported with higher frequency in the treatment group and is believed to be due to the vaccine.
What is mRNA and how does the vaccine work?
Messenger RNA, or mRNA, is a temporary version of DNA. In the human body, it is a single strand that is created as a complimentary copy of a piece of DNA. Then it is transported out of the nucleus, where DNA is housed, and used to make proteins. The end of the process results in destruction of the mRNA but production of a protein. Our bodies perform this process all the time.
The vaccines developed by Pfizer and Moderna use this process to create immunity. They inject mRNA that is coded with the “crown” or spike protein of the coronavirus. Our cells take this mRNA and produce the spike protein then display it on the surface. At that point, our immune system recognizes it as a foreign protein and begins developing an immune response. This process has been studied for a long time and its use in vaccines was first described in 1989. Since then, multiple experimental models have been created in attempt to successfully use mRNA. There is an excellent accounting of its history in “The Story of mRNA” from STAT.
Unlike other vaccines which rely on injection of killed or weakened particles, mRNA vaccines inject only the information necessary for our own bodies to create a piece of the virus. This piece, the coronavirus spike protein, is then replicated in our cells and presented to out immune system without any of the live virus having to infect us. Similar vaccines were studied for influenza, zika, rabies, and cytomegalovirus (CNV). Though none of these vaccines made it to production, the science of mRNA vaccines was furthered by each attempt.
Today we are finally realizing the full potential of mRNA vaccines. As we begin the process of vaccinating the country, many questions regarding this type of vaccine will arise. The CDC’s page on “Understanding mRNA COVID-19 Vaccines” and the University of Cambridge’s page “RNA vaccines: an introduction” are excellent resource. In addition, I recommend reading “mRNA vaccines — a new era in vaccinology ” in Nature Reviews Drug Discovery.
Sign up to receive this free newsletter weekly here.