In December of 2020, Pfeizer’s vaccine against COVID-19 disease received an Emergency Use Authorization in several countries.
In the middle of the deadly coronavirus pandemic that caused a health crisis worldwide, the health authorities decided that the vaccine’s known potential benefits outweigh known potential risks.
Given that this vaccine is based on an entirely new platform (mRNA) and was discovered and tested in a record time, it is understandable that many doubts exist about its safety. In this article, I will review published data about the vaccine. I will use materials provided by the British medical regulatory agency (MHRA) and by the US regulatory agency FDA.
I wrote this article in 12/2020, so if you are reading it many months later, please seek more up to date information.
I plan to concentrate mainly on safety. If you need a broader overview of this vaccine, you can watch my YouTube video. There, you will find information on the mechanism of action, effectiveness, and general safety.
How was this vaccine studied?
The vaccine was studied in multiple countries (USA, Argentina, Brazil, Germany, S.Africa, Turkey) in phase 1, 2, 3 human clinical trials. In total, over 20 thousand volunteers received the vaccine and 20K people were given a placebo. In phase 1, a total of 90 healthy individuals at age 18-85 were studied. Phase 1 aimed to choose the dose and watch for immune response and any significant adverse effects.
After choosing the dose, the vaccine was further tested in a 2/3 phase clinical study on participants 12 years and older (safety and efficacy was evaluated on approximately 40 thousand volunteers). At this stage, volunteers at higher risk of acquiring COVID-19 disease were studied as well. Chronic conditions such as autoimmune disease, hypertension, asthma, diabetes, HIV, Hepatitis B, or C were represented among participants in those phases, too. Importantly, these chronic conditions had to be stable.
The vaccine was given in two doses, 21 days apart. The median time of follow-up was only two months after the second dose (for 18 thousand vaccine recipients; additional 2 thousand recipients had shorter follow-up). This duration of the follow-up may seem short; however, historically, most immune-mediated adverse effects related to vaccine administration show up within six weeks after injection.
The trial had an excellent rate of retaining participants in the study. It speaks to the dedication of the volunteers and possibly to not so harmful side effects. Out of 21823 subjects randomized into the vaccine group, 20566 (94.2%) volunteers received both vaccine doses.
All ages and races were represented well in the trials (see tables 1 and 2). You can see in Table 1 that almost 42% of participants were older than 55 years of age. It is crucial information because historically, some vaccines stimulated weaker responses in senior citizens than in younger ones, and as we know, COVID-19 disease is most deadly for older people.
Table 1.
| Age of recipients: | Vaccine Group | Placebo Group |
| Age 16 to <18 | 77 (0.4%) | 76 (0.4%) |
| Age 16 to <55 | 11589 (57.8%) | 11743 (58%) |
| Age >55 | 8396 (41.9%) | 8454 (41.8%) |
| Age =/> 65 | 4294 (21.4%) | 4319 (21.3%) |
| Age =/> 75 | 860 (4.3%) | 852 (4.2%) |
In Table 2, you should notice that 82% of participants were white and reminder were from other racial groups.
Table 2.
| Race of recipients: | Vaccine Group | Placebo Group |
| White | 16387 (81.8%) | 16619 (82.1%) |
| Multiracial | 523 (2.6%) | 493 (2.4%) |
| Black or AA | 1957 (9.8%) | 1972 (9.7%) |
| Asian | 880 (4.4%) | 883 (4.4%) |
What are indications for the use of this vaccine?
Under the proposed Emergency Use Authorization (EUA), Pfizer’s vaccine will be recommended for use in individuals 16 years of age and older for the prevention of COVID-19 disease.
Pfizer’s vaccine is not recommended for anybody with a history of a severe allergic reaction to any component of this product.
Please read carefully all indications and contraindications to this vaccine from FDA prescribing guidance and manufacturer’s documents.
Indications and contraindications will likely be modified frequently as we learn more from new and ongoing clinical trials. Additionally, we will acquire more information from many more people exposed to this new product after mass vaccination efforts.
What are known safety issues after the administration of Pfizer’s COVID-19 vaccine?
Local Reactions
In Table 3, I included the most important injection site local effects that occurred within seven days after administration of the vaccine. Pain at the injection site, redness, and swelling; all have been described to occur quite commonly. Interestingly, more reactions and more severe reactions occurred with the second dose and among younger participants.
Table 3. Local symptoms that occurred after vaccine injection within 7 days for both doses and two different age groups.
| Symptom | Dose 1 18-55 y/o | Dose 2 18-55 y/o | Dose 1 >55 y/o | Dose 2 >55 y/o |
| Any Pain | 83% | 78% | 71% | 66% |
| Severe Pain | 1% | 1.2% | 0.2% | 0.5% |
| Any Redness | 4.5% | 5.9% | 4.7% | 7.2% |
| Severe Redness | 0.3% | 0.5% | 0.2% | 0.5% |
| Any Swelling | 5.8% | 6.3% | 6.5% | 7.5% |
| Severe Swelling | 0.2% | 0.3% | 0.1% | 0.2% |
I want to emphasize that severe pain, severe redness, and extreme swelling affected only less than 1.5% of volunteers. Please, note that I did not include frequencies of these symptoms among placebo groups as those were significantly lower. In the end, for us who will be receiving the vaccine, it only matters how many of us will be affected and how severely.
Systemic Adverse Events
Fever
Fever can be a very unpleasant effect of vaccination. It may make us stay at home, lose workday, and at times may require treatment. Table 4 shows how many vaccine recipients in two different age groups were affected by elevated body temperature to 38 °C or more. 16% of younger volunteers (18-55 y/o) developed such fever after the second dose, and 11% of older folks did the same. Again, the common theme is true here as well. Younger people got affected more, and the second dose resulted in more unpleasant reactions than the first one.
Table 4. Fever and use of anti-pyretic and anti-pain medications after both doses in two different age group within 7 days after administration of vaccines.
| Fever | Dose 1 18-55 y/o | Dose 2 18-55 y/o | Dose 1 >55 y/o | Dose 2 >55 y/o |
| 38 °C or more | 3.7% | 15.8% | 1.4% | 10.9% |
| 39-40 °C | 0.3% | 1.2% | 0.1% | 0.3% |
| More than 40 °C | 0% | 0% | 0.1% | 0% |
| Use of medications for fever & pain | 27.8% | 45% | 20% | 38% |
I want to underline that only 1.2% of younger participants and 0.3% of older had fevers 39 °C or higher. It is startling that 45% of younger participants and 38% of older ones decided to use anti-fever and -pain medications after the second dose.
Other systemic symptoms
Many recipients of the vaccine complained of other systemic effects occurring within seven days of the vaccine administration. The list included fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and joint pain. All symptoms were mostly mild or moderate and more frequent after the second dose. You can see an incidence of each particular sign in Table 5.
Table 5. General symptoms occurring within 7 days after administration of the vaccine. For each dose, there are two values provided. The first value is for the age range 18 – 55 years of age, and the second value for ages above 55.
| Symptom | Dose 1 | Dose 2 |
| Fatigue | 47%—34% | 59%—51% |
| Headache | 42%—25% | 52%—39% |
| Chills | 14%—6.3% | 35%—23% |
| Vomiting | 1.2%—0.5% | 1.9%—0.7% |
| Diarrhea | 11%—8.2% | 10%—8.3% |
| New or worsened muscle pain | 21%—14% | 37%—29% |
| New or worsened joint pain | 11%—9% | 22%—20% |
Non-serious adverse events that occurred at any time after vaccinations
All local reactions and systemic effects of the vaccine were also found beyond the critical period of seven days from vaccination, but they presented with significantly lesser frequency. In addition, lymphadenopathy and Bell’s palsy occurred more frequently in the vaccinated group.
Lymphadenopathy
There were 64 cases of enlarged lymph nodes in the vaccine group compared to 6 cases in the placebo group. This imbalance might be due to an immune system reacting after vaccine administration.
Bell’s palsy
Four participants in the vaccine group reported Bell’s palsy, and nobody in the placebo group suffered from the same condition. Bell’s palsy is described as usually temporary weakness or paralysis of facial muscles. Notably, the reported frequency of Bell’s palsy in the vaccine group is consistent with the general population’s background rate. However, once the vaccine is rolled out to the broader public, surveillance for this condition may bring us more information.
Serious Adverse Events
Deaths
Whenever we study any new vaccine or medications, we want to determine whether it contributes to increased mortality rates.
There were six incidences of death during the trials, 2 in the vaccine group, and 4 in the placebo group. Five cases of death occurred in individuals older than 55. The study groups’ mortality rates were similar to what would be expected in the general populations with similar age distribution.
Non-fatal Serious Adverse Events
Rates of non-fatal serious adverse events were only 0.6% in the vaccine group and 0.5% in the placebo group.
Comparing to the placebo group, participants who received the vaccine had a slightly higher incidence of appendicitis (0.04%), acute myocardial infarction (0.02%), and cerebrovascular accident (0.02%).
Comparing to the vaccine group, Individuals from the placebo group had a higher incidence of pneumonia (0.03%), atrial fibrillation (0.02%), and syncope (0.02%).
Laboratory abnormalities
During the phase 1 trial, some participants who received the vaccine had a transient decrease in the numbers of lymphocytes in their blood tests. This finding was temporary and not associated with any clinical symptoms.
What we don’t know about Pfizer’s vaccine?
What is the duration of protection?
The vaccine was studied for only 2-3 months, a little longer on a small number of individuals from phase 1 clinical trial. It is challenging to predict how long acquired immunity will last. We know from epidemiological studies of people who had COVID-19 disease that their antibody levels tended to decrease after 3-6 months, sometimes were even undetectable. Some of these individuals got reinfected, albeit not in large numbers from what we know.
Will vaccinated individuals preserve cellular immunity even if their humoral immunity (via neutralizing antibodies) wanes?
If we decide that yearly vaccinations will be necessary, we need to determine how people will respond to 3rd exposure to the same vaccine. So far, we observed that the second dose was associated with an increased number of local reactions and fevers when compared to the first dose. These questions will require careful study in the future.
What are the effects of the vaccine on pregnant women and breastfeeding mothers?
We do not know the effects of the vaccine on pregnant women. Does the immunization pass through the placenta to the fetus? Does it cause any inflammatory reactions in the fetus? Those are fundamental questions to answer given how immunogenic this vaccine is in young individuals causing fevers and other inflammatory symptoms.
Also, we don’t know if the vaccine passes into breast milk, and if breastfeeding baby consumes it, would it affect those newborns?
What is its effectiveness and safety in children?
We do not know the effects of this vaccine on children. The youngest subjects in the clinical trials were children 12 years of age. However, there were only about 100 children enrolled between ages 12-16. That’s why the vaccine is recommended at this time only to individuals 16 years old or older.
What are the long term effects, and are there any rare consequences?
Due to the limited total time, we followed volunteers after vaccinations, we do not know the long-term effects and rare side effects or conditions from the vaccine. It is essential because it is a novel mRNA vaccine. Pfizer is planning to monitor all volunteers from the trials for a total of 24 months.
Rare side effects or associated conditions can’t be excluded due to the low number of participants in the trials (only around 20 000 people received the vaccine so far). In the past, we had rare conditions occurring with other vaccines (with frequency lesser than 1 in 50 000 recipients). For example, Guillain – Barre Syndrome (a neurologic disease) was described to occur in 1 per 100 000 cases after swine flu vaccinations in 1976.
So, Is Pfizer’s coronavirus vaccine safe for me?
I will not answer this question directly because my article is not supposed to fetch you medical advice. However, let’s go through a few essential reasoning steps.
The vaccine received an Emergency Use Authorization (EUA) in several countries and not a typical full approval that we desire to have whenever we want to use a new pharmaceutical. The EUA means that under conditions of a health crisis, authorities and pharmaceutical companies conducted somewhat limited studies compared to standard processes. But, they still decided that the known benefits of the vaccine outweigh known potential risks.
The authorities also designed a further and ongoing plan for the vaccine sponsor (Pfizer) with which the company will have to comply. The program will include continuing observation of people who received the vaccine for at least a total of 24 months. There is also a suggestion to have in trials more people with underlying conditions.
In clinical trials, approximately 20 thousand people received the vaccine so far (an additional 20K in the placebo group). Recipients did not complain of any unusual symptoms that would not be expected after the vaccine. The majority of symptoms were expected, although stronger than after other vaccines such as the flu vaccine.
It means that this vaccine stimulates a strong immunologic reaction. In a way, it is good because thanks to that it is very effective. On the other hand, we would like to have a longer follow-up and larger groups of patients with underlying conditions such as autoimmune, allergic, and neurologic diseases. Given that the “hyperactive immune system” mediates these conditions, it would reassure the public that the vaccine will not make you come down with those diseases or make your existing “immune disease” worse.
A few cases of Bell’s palsy were described that did not occur in the placebo group; however, its incidence was still similar to the frequency expected in the general population.
There were few more cases of enlarged lymph nodes and appendicitis in the vaccine group, but their numbers were not out of the range for normal populations.
In my opinion, if you are a healthy person and first in line to be given this vaccine, read all information and decide for yourself. As a health worker, I am in that group and will probably get access to it soon. Since I do not have any significant medical issues that I know of, I plan to take it.
If I had a condition where the immune mechanism plays a significant role, I would wait for additional 2-3 months. By then, we will have more anecdotal information on several millions of recipients. That way, I would feel safe to take it. But again, my decision probably would have been different if I were 75 years old with such an autoimmune condition and living in a senior living facility. As you can see, everything depends on the balance of the risks and benefits for each person.
I think it would be best if you had a trusted doctor who would take time to learn everything available on this subject and then had a discussion with you considering all potential benefits and risks that exist for your health situation.
In summary, I think that the invention of the vaccine protecting us from the coronavirus causing COVID-19 disease is one of humankind’s greatest achievements. At this time, health authorities gave only Emergency Use Authorization. We should monitor all people receiving the vaccine to reassure ourselves and society that it is very safe and not associated with any rare side effects that we did not detect in somewhat limited clinical trials.