COVID-19 vaccination

Several people have asked me questions regarding the new COVID-19 vaccinations, such as: what is in them? do they work? what are the side effects? And should I get vaccinated if I want to get pregnant in 2 years? I will answer these questions here, based on the scientific data currently available. Let me know in case you have other questions.

= I am a molecular geneticist and a certified immunologist (check my resume). I have no financial or other interest in any of the vaccines discussed below. I do occasionaly work with a large pharmaceutical company that produces vaccines, but this company has no involvement in the development or production of the vaccines discussed below.=

Since the start of the COVID-19 pandemic many research institutes and biotech companies started with the development of COVID-19 vaccines (221 vaccines are in development). Only a few of the vaccines developed so far have been or are almost approved for (emergency) use. These are:

• BNT162b2/Comirnaty by Pfizer & BioNTech (USA/Germany). This vaccine is an mRNA based vaccine that requires two doses 21 days apart. It has been approved in 21 countries so far, among others in the US, EU, UK, Mexico, and Israel for people 16 years and older. In a phase III trial that included 43,448 people, 95% reduction of COVID-19 was found in vaccinated people compared to non-vaccinated people. Of the vaccinated people that did develop COVID-19 one had severe COVID-19, in the control group there were nine with severe COVID-19.
• mRNA-1273 by Moderna (USA). This is also an mRNA based vaccine that requires two doses, 28 day apart. It has been approved in among others the US, Canada, EU, and Israel for people 18 years and older. In a phase III trial that included 30,000 people, 94.1% reduction of COVID-19 was found in vaccinated people compared to non-vaccinated people. These data are not published yet but have been reviewed by the NIH.
• Sputnik V by GRIEM (Russia). This vaccine is based on a viral vector and requires two doses 21 days apart. It has been approved in the Russian Federation, Belarus, Argentina, Serbia, Hungary, and Bolivia. In a phase III trial that included 19,866 people, a 91.6 % reduction of COVID-19 was found in vaccinated people compared to non-vaccinated people.
• The AZD1222/Vaxzevria vaccine by Oxford University & AstraZeneca has been approved in the UK, EU, India, and Mexico. This vaccine is based on a viral vector. Preliminary phase III trial data that included 23,848 people are very good: depending on the dose 62% to 90% reduction of COVID-19 was found in vaccinated people compared to control people (that were vaccinated with another vaccine or placebo). After the second dose 10 people in the control group were hospitalized due to COVID-19, two of which developed severe COVID-19, and one of them died. No one in the vaccinated group was hospitalized due to COVID-19 or developed severe COVID-19. This vaccine is very promising because it can be stored at normal refrigeration temperatures.
• The Ad26.COV2.S Johnson & Johnson vaccine (US/Netherlands). This vaccine is based on a viral vector and requires only one dose. It has been approved for use in the USA and Canada for people 18 years and older. In a phase III trial that included 43,738 people it was found to give 66.1% reduction of COVID-19 at 28 days after vaccination (data reviewed by the FDA). According to data provided by the manufacturer, it is 85% effective in prevention of severe COVID-19 (hospitalization and death) at 28 days after vaccination.
• Three vaccines from China have been approved for use in China and several other countries. I will not go into these in detail since I dont think these will be available any time soon on the Western market.

Note 1: If you have had a severe allergic reaction —also known as anaphylaxis— to any ingredient in the COVID-19 vaccine, you should not get vaccinated with a vaccine that contains that ingredient. Choose together with a doctor a vaccine that does not contain the ingredient you are allergic to. See lower on this page for ingredients. Note 2: some people are advised to wait to get vaccinated, see question 15 below.

Questions

1) Is it possible to develop COVID-19 disease from the vaccine?

No. The Pfizer, Moderna, Sputnik V, Oxford/AstraZeneca, and Johnson & Johnson vaccines do not contain the SARS-CoV-2 virus that causes COVID-19, so it is impossible to develop COVID-19 from these.

2) What are the side effects of the COVID-19 vaccination?

In general, vaccines (such as the flu vaccine) often have the following side effects: pain at the injection site, tiredness, headache, muscle pain, chills, joint pain, and fever. These side effects are normal signs of activation of the immune system.  It is very, very rare to develop a severe allergic reaction to one of the ingredients (most vaccines: 1 in 1,000,000 people).

Pfizer vaccine: The vaccine was given to 22,000 people in the clinical trial. The most commonly reported side effects, which typically lasted several days, were: pain at the injection site (84.1%), tiredness (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), and fever (14.2%). Severe side effects were seen in less than 0.05%. People who were known to have severe allergic reactions in the past to any other vaccine or injectable were however excluded form the study. By 23-12-2020 about 1.9 million people had been vaccinated with this vaccine in the US of which twenty-one developed severe allergic reactions, possibly to polyethylene glycol (PEG). Of these 21, most were treated at emergency departments while four were hospitalized, 20 are known to have recovered at the time of the report.

Moderna vaccine: most frequently reported side effects during the clinical trial included: pain at the injection site (88.8%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), chills (43.4%), joint pain (44.8%), and fever (14.8%). Severe side effects were seen in less than 0.1% of vaccinated people. Fewer people have been vaccinated with the Moderna vaccine so far, one person developed a severe allergic reaction.

Sputnik V vaccine: At the time of analysis of the clinical trial data, 14,964 people had received two doses of the vaccine. The most frequently reported side effects during the clinical trial included: flu-like illness, injection site reactiosn, headache, and lack of energy (numbers or percentages are not provided). Severe side effects were seen in 0.4% of vaccinated people. No vaccine-related deaths were reported (0.0002% of people died in both the vaccine and control group).

Oxord/AstraZeneca vaccine: For the safety analysis, clinical data were analyzed from 12,021 people who received two doses of the covid-19 vaccine and 11,724 people in the control group (who received two doses of a control vaccine or a placebo). Serious side effects were seen in less than 0.7% of vaccinated people and less than 0.8% of the control group. Frequently reported side effects were not mentioned in this publication, but they were mentioned in two previous publications with smaller numbers of participants (here and here). Injection site pain, flu-like symptoms, muscle pain and headache were the most frequently reported adverse reactions and were reported less frequently in older adults (<55 years old) than in younger adults. A few thrombosis cases, that after vaccination of millions of people briefly caused panic, turned out not to be caused by the vaccine.

Johnson & Johnson vaccine: During the phase III trail nearly 22,000 people received the vaccine. The most common side effects were: injection site reaction, headache, fatigue, muscle pain, nausea, and fever. Data of the trail have however not been published yet, so exact numbers are still lacking.

3) Are these vaccines safe in pregnant or breast-feeding women?

None of these vaccines have been tested thus far in pregnant or breast-feeding women. This does not mean they are not safe. ‘Those who are pregnant should choose whether to be vaccinated after discussing the risks and benefits with their physicians.’ However, pregnant people with COVID-19 have an increased risk of severe illness and preterm birth.

A great benefit of breastfeeding is that the antibodies a mother makes in response to a vaccine (as well as all other antibodies she makes) are transfered via the milk to the baby, thus protecting the baby. Some vaccinations, namely those against influenza and pertussis, are even especially given to pregnant women to protect their baby after birth against these diseases that may be life-threatening to babies.

4) Can I take this vaccine if I want to get pregnant in a year from now?

There is no data whatsoever to indicate that any type of vaccination would affect a future pregnancy or the baby born from it. There is no reason to assume that this would be different for COVID-19 vaccines.

5) How can COVID-19 vaccines be developed so fast while vaccine development usually takes years?

Vaccine development is indeed usually a slow process and takes many years. There are several reasons why the development and approval process was now faster:

a) Because of the SARS-CoV-2 pandemic many institutes dropped all other work to focus entirely on developing COVID-19 vaccines (dedicating all scientists, materials, lab space, money, etc).

b) Governments worldwide have also made a lot of money available for the development of these vaccines. Usually, research institutes need years to obtain money for each step.

c) In the past some efforts were already made to generate vaccines against coronaviruses, namely the coronaviruses that cause SARS and MERS. Those vaccines were never finished because the SARS and MERS epidemics died out, but the knowledge that was gained was not lost.

d) Agencies involved in the approval (FDA, EMA, etc) that usually take many months to decide on new drugs gave priority to the approval process, dropping all other work for this.

e) Normally when a new vaccine is developed it takes a long time to test. This is because you need to prove you can prevent a lot of cases while the disease it targets may not be very common, so the disease does need to occur in many people in your control group. For COVID-19 this is currently not a problem as prevalence is very high worldwide.

Note: The Pfizer, Moderna, Oxford, Sputnik V, and Janssen vaccines have been going through the complete testing process, of some of the other vaccines this is not (yet) clear.

6) Why are COVID-19 vaccines developed so slow while flu vaccines only take a few months?

Flu vaccine manufacturers use the same process each year to make the annual seasonal flu vaccine, thus saving valuable time.  The coronavirus that causes COVID-19 is a new virus, so new vaccines are developed and tested to ensure they work and are safe.

7) If I already had COVID-19 should I still get a COVID-19 vaccination?

Yes. Most people build up good immunity after two doses of vaccination, which is likely better than the immunity you build up after one natural infection. And anyway, it certainly does not hurt to get vaccinated in addition.

8) Can I stop wearing a mask after I get vaccinated?

No. It is better if everyone keeps on respecting rules such as wearing a mask, keeping a safe distance, meeting few people, until the pandemic is under control. This is because the vaccines do not provide a 100% protection. When the efficacy of a vaccine is 95%, this means 5% of vaccinated people can still develop COVID-19 when infected, and you do not know whether you are part of that 5%. Once the large majority of people are vaccinated, herd immunity will also protect those that could not be vaccinated and the 5% in which the vaccination did not work.

In addition, we now know that most vaccinated people are protected from developing COVID-19. We also expect that vaccinated people do not transmit the SARS-CoV-2 virus, but this has not been proven yet.

9) How much does the COVID-19 vaccination cost?

As far as I know the vaccinations will be provided for free by most governments. I specifically verified this for the US, Japan, India, Norway, France, Indonesia, The Netherlands, UK, Israel, and Mexico. If you want to know how much some of the governments pay for the vaccines read this article.

10) What is the efficacy and safety of these vaccines in people over 70 with pre-existing conditions?

Safety: The Pfizer vaccine was trialed in 43,458 people of 16 years and older, about 42% of those were more than 55 years old, and the age range was 16 to 91. Of all participants 20.5% had comorbidities (diabetes, chronic lung disease, cancer, heart disease, etc). Younger people (16-55) consistently reported more side effects (injection site pain, fatigue, headache, fever, etc) than older people. In the vaccinated group 0.6% experienced severe adverse events (events that require hospitalization and intervention), in the control group 0.5%. In both the vaccinated and the control group 0.1% experienced life-threatening events, two died in the vaccinated group and four in the control group. So, the adverse events were not shown separately for older people with comorbidities, but they were low in general, and not really different between vaccinated and controls.

Efficacy: The Pfizer vaccine had an efficacy overall of 95%. Obesity (BMI ≥ 30) is an important risk factor for developing severe COVID-19. They analysed efficacy in people at risk (with any comorbidity and/or obesity): in those 16–64 and not at risk efficacy was 94.2%. In those 16–64 and at risk it was 95.9%, in those ≥65 and not at risk it was 100%, in those ≥65 and at risk it was 91.7%. They also analysed the effect of obesity on efficacy separately: In those 16–64 and not obese this was 95.2%, in those 16–64 and obese this was 94.9%, in the ≥65 and not obese this was 91.8%, and in those ≥65 and obese this was 100%. In conclusion, the efficacy is also pretty good in older people with comorbidities.

Safety: The Moderna vaccine was trialed in 28,207 people of 18 years and older, about 25% of those were 65 years and older, and the age range was 18 to 95. Of the people under 65 some 16.7% had high-risk chronic diseases, of the older people this was not specified. In both the vaccinated group and the control group 1% experienced severe adverse events (events that require hospitalization and intervention). No subgroup analyses of adverse events in older people with/without comorbidities were performed yet.

Efficacy: The Moderna vaccine had an efficacy overall of 94.1%. In those 18–64 year old and not at risk it was 95.9%, in those 18-64 year old and at risk it was 94.4%, and in those ≥65 it was 86.4%.

Safety: The Oxford vaccine was trialed in 23,745 people of 18 years and older, 9.7% were 65 years of age or older. Of all participants 24.7% of people had comorbidities (BMI ≥ 30, cardiovascular disorder, respiratory disease, or diabetes). Adverse reactions were generally milder and reported less frequently in older adults (≥65 years old). No subgroup analyses of adverse events in older people with/without comorbidities were performed yet.

Efficacy: The Oxford vaccine had an efficacy overall of 70.4% when cosidering both those vaccinated with low dose and standard dose. Separate results of elderly people after both doses are not available yet, but after dose 1 it is 76%. In people with comorbidities efficacy was 73.4%.

Safety: The Sputnik V vaccine was trialed in 19,866 particpants, 10.8% of those were over 60 years of age (up to 87 years). Comorbidities such as diabetes, hypertension, ischemic hearts disease, and obesity were present in 46.6% of participants over 60 years of age. The most commone adverse events were flu-like illness (15.2%) and local reaction (5.4%).

Efficacy: The Sputnik V vaccine had an efficacy overall of 91.6% in participants over 18 years old. In those 18–60 year old it was 90.0-92.7%, and in those >60 it was 91.8%.

For the Johnson & Johnson vaccine these data have not been published yet.

11) If I have allergies, can I safely take the COVID-19 vaccine?

There were no severe allergic reactions in the Pfizer and Moderna trials. People with all sorts of allergies were included in the studies (except for people with severe allergic reactions in the past to any other vaccine or injectable). The Pfizer trial included 6000 people with allergies (like pollen allergy, food allergy, all the way up to anaphylaxis).

According to the Centers for Disease Control and Prevention (CDC) allergic reactions (including severe allergic reactions) not related to vaccines or injectable therapies are not a contraindication or precaution to vaccination with either the Pfizer or Moderna vaccine.

12) How long will the vaccinations protect us?

About a week after the second dose the maximum protection is achieved. We dont know yet how long this protection will last. For some vaccines the protection lasts for 10 years (for instance: tetanus vaccine), others provide lifelong protection (for instance: the shingles vaccine).

At least 70 to 75 per cent of the population will have to be immunized to control the spread of the virus.

13) Will the vaccines also work against the mutated viruses from Great-Britain and South-Africa?

The Spike protein of the SARS-CoV-2 virus against which the Pfizer, Moderna, Sputnik V, Oxford, and Johnson & Johnson vaccines are directed consists of 1273 amino acids (‘building blocks’), 10 of which are changed in the British variant (B.1.1.7), and 9 to 10 are changed in the South-African variant (501.V2). Proteins are cut into small pieces by your immune system before antibodies are made against them, the majority of the pieces of the original Spike protein will still be the same as the mutated proteins. So in theory the effect should be small.

However, some parts of the Spike protein are more important for making good antibodies than others. Pfizer has therefore tested in the lab whether a change in the amino acid (N501) present in both the British and South African variant would be less well recognized by people who have been vaccinated with their vaccine. That turns out not to be the case. However, the South African variant also changes an amino acid (E484) that may have an effect on antibody recognition, but they have done so with material from people who have gone through COVID-19, not material from vaccinated people. More research is needed on this.

14) Am I already protected after the first vaccination dose?

Yes and No. Immediately after the first dose you are not protected at all, it takes about two weeks until a ~80% reduction of COVID-19 cases is reached with the Pfizer vaccine, and 74% reduction with the Sputnik V vaccine. In general, after this type of vaccination, if a second dose is not given after 3 to 6 weeks, the protection will slowly decline. For the Moderna, and Oxford vaccines these data are not available yet.

15) When should vaccination be postponed?

If you just had COVID-19 or a positive COVID-19 test, you should wait 90 days. If you dont feel well, you should wait until the symptoms are resolved. If you just received another vaccination, you should wait 14 days. If you are in quarantine because you were in contact with someone who was positive, wait until after your quarantine period is over.

You should NOT get the COVID-19 vaccine at all: If you ever had a severe allergic reaction —also known as anaphylaxis— to any ingredient in the COVID19 vaccine, or if your health is so bad (basically if you are terminally ill) that a couple of days of fever or diarrhea might kill you.

In Norway, several very old, terminally ill patients died after receiving the vaccine. The side effects of the vaccine (fever, diarrhea, vomiting) were probably too much for them.

15) In some countries the second dose is delayed, is that harmful?

In order to protect everyone as soon as possible, in some countries the second dose of vaccines (of which two doses are required) is postponed. The three to four weeks recommended by most manufacturers is the interval tested for these vaccines, there has been no time in the development phase to extensively test the ideal number of weeks between the first and second dose, and three a four weeks works well for many other vaccines. In practice, waiting a few extra weeks does not appear to be a problem.

In a small study of people over 80 who received their second Pfizer dose at 3 or 12 weeks, it was found that the people who did not receive the second dose until after 12 weeks, the final amount of antibodies they made against SARS-CoV-2 was 3.5 times greater than in the people who got their second dose after 3 weeks. Of course, this study does not answer the question whether you are well protected between the first and second dose, but the result will become very interesting if a longer interval between the first and second dose does not appear to be a problem.

Ingredients of the vaccines

The ingredients of the Pfizer and Moderna vaccines are very similar (see image above).

The Pfizer vaccine contains:

Active ingredient:

•  nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2. RNA is a template to produce a specific protein. In the vaccine, this message tells our cells to produce the viral protein that will trigger the immune response to the virus

Lipids:

• (4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis (ALC-3015)
• (2- hexyldecanoate),2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159)
• 1,2-distearoyl-snglycero-3-phosphocholine (DSPC)
• Cholesterol

These are fancy words for four different fatty molecules. These assemble into capsules that contain the RNA. These fats aid in delivery and protection of the RNA.

Salts:

• potassium chloride
• monobasic potassium phosphate
• sodium chloride
• basic sodium phosphate dihydrate

Again, fancy words for four salts. This formula is actually phosphate-buffered saline (PBS), a common buffer. This normalizes the pH of the vaccine. Sodium chloride you probably know as kitchen salt, potassium chloride is sometimes used as a substitute for regular salt by people with high blood pressure.

Sugar:

• sucrose

Just sugar! It is a cryoprotectant to ensure the lipids don’t get too sticky in ultra-cold storage.

The Moderna vaccine contains:

Active ingredient:

•  synthetic messenger ribonucleic acid (mRNA) encoding the pre-fusion stabilized spike glycoprotein (S) of SARS-CoV-2 virus. RNA is a template to produce a specific protein. In the vaccine, this message tells our cells to produce the viral protein that will trigger the immune response to the virus.

Lipids:

• SM-102
• 1,2-dimyristoyl-rac-glycero3-methoxypolyethylene glycol-2000 (PEG2000-DMG)
• 1,2-distearoyl-snglycero-3-phosphocholine (DSPC)
• Cholesterol

These are fancy-sounding words for four different fat molecules. These fatty molecules assemble into little capsules that contain the RNA. These fats aid in delivery and protection of the RNA, as RNA is unstable by itself. Two of these, DSPC and cholesterol, are also found in the Pfizer vaccine.

Buffers:

• tromethamine (Tris)
• tromethamine hydrochloride (Tris HCl)
• acetic acid
• sodium acetate

These four solutions work in pairs as buffers. Together, these make a solution called Tris-Acetate buffer, a commonly used solution especially when using RNA. Buffers normalize the pH of the vaccine so that it matches the pH of our bodies. This solution is slightly different than the Pfizer formulation, but serves the same purpose.

Sugar:

• sucrose

Just sugar! Again, used as a cryoprotectant and stabilizer. Because this vaccine is stored in cold conditions (-20C) for long-term storage, sugar ensures the lipids don’t get too “sticky” in the cold.

The Sputnik V vaccine contains:

Active ingredient:

The vaccine is made from a weakened version of a common cold virus (adenovirus) that has been changed so that it can’t grow in humans. Genetic material from the SARS-CoV-2 coronavirus called Spike glycoprotein has been added to the virus. This Spike protein is present on the surface of SARS-CoV-2 and plays an essential role in the infection pathway of the SARS-CoV-2 virus. The Sputnik V vaccine approach is unusual in that it uses two different vaccines for the first and second vaccination dose. Both are based on adenoviruses (Ad26 and Ad5) that contain Spike protein as described above.

Buffers:

• Tris (hydroxymethyl) aminomethane

Salts:

• sodium chloride
• magnesium chloride hexahydrate
• EDTA disodium salt dihydrate

Lipids:

• polysorbate-80

Alcohol:

• ethanol 95%

Sugar:

• sucrose

The Oxford vaccine contains:

•  The vaccine is -similar to the Sputnik V vaccine- made from a weakened version of a common cold virus (adenovirus). This adenovirus (ChAdOx1) normally causes infections in chimpanzees, and has been changed so that it can’t grow in humans. Genetic material from the SARS-CoV-2 coronavirus called Spike glycoprotein has been added to the virus. This Spike protein is present on the surface of SARS-CoV-2 and plays an essential role in the infection pathway of the SARS-CoV-2 virus.

Aminoacids:

• L-histidine
• L-histidine hydrochloride monohydrate

Histidine is an amino acid. Amino acids are the building blocks of proteins, and histidine is one of the amino acids that we do not make ourselves but that we get through our food.

Stabilizer:

• polysorbate 80

Polysorbate 80 is used for stabilizing aqueous liquids that are injected. It is widely used in vaccines. It is also used as an emulsifier in foods and some cosmetics.

Alcohol:

• ethanol

Salts:

• magnesium chloride hexahydrate
• sodium chloride
• disodium edetate dihydrate

Sugar:

• sucrose

The Johnson & Johnson vaccine contains:

Active ingredient:

• The vaccine is -similar to the Sputnik V and Oxford vaccines- made from a weakened version of a common cold virus (adenovirus). This adenovirus (Ad26) normally causes the common cold. Genetic material from the SARS-CoV-2 coronavirus called Spike glycoprotein has been added to the virus. This Spike protein is present on the surface of SARS-CoV-2 and plays an essential role in the infection pathway of the SARS-CoV-2 virus.

Salts:

• sodium chloride

Buffers:

• citric acid monohydrate
• trisodium citrate dihydrate

Stabilizer:

• polysorbate-80
• 2-hydroxypropyl-β-cyclodextrin
• ethanol

Other:

• may also contain residual amounts of host cell proteins and/or host cell DNA

For comparison, Flu vaccines contain:

Note: several companies produce flu vaccines, these flu vaccines have different ingredients.

a) The most common ingredients in flu vaccines (for vaccines based on influenza virus grown in fertilized chicken eggs):

Inactivated influenza viruses

Formaldehyde – a chemical typically present in the human body, which is also a product of healthy digestive function. Formaldehyde inactivates toxins from viruses and bacteria that may contaminate the vaccine during production.

Aluminum salts – Aluminum salts are adjuvants — they help the body develop a stronger immune response against the virus in the vaccine. Aluminum salts are also in drinking water and various health products, such as antacids and antiperspirants. They are not always present in flu vaccines.

Thimerosal is a preservative, and it keeps vaccines from becoming contaminated. It comes from an organic form of mercury called ethylmercury, a safe compound that does not remain in the body. Thimerosal is only added to multi-dose vials.

Chicken egg proteins – these proteins help the viruses grow before they go into the vaccine.

Gelatin is present in the flu shot as a stabilizer — it keeps the vaccine effective from the point of production to the moment of use. Most flu vaccines use pork-based gelatin as a stabilizer.

Antibiotics in flu vaccines keep bacteria from growing during the production and storage of the products. Vaccines do not contain antibiotics that can cause severe reactions, such as penicillin.

b) The ingredients in flu vaccine (for vaccine based on recombinant proteins):

Note: this is an uncommon flu vaccine (Flublok). It contains no egg proteins, antibiotics, or preservatives.

Influenza proteins – produced with the help of a viral vector in an insect cell line

Salts – namely: sodium chloride, monobasic sodium phosphate, dibasic sodium phosphate (similar to Pfizer vaccine)

Lipid – polysorbate 20 (Tween®20) which contains polyethylene glycol

may also contain residual amounts of baculovirus and insect cell proteins and DNA, and Triton X-100.