With over 40% of its population vaccinated (CDC, 2021), the ongoing COVID-19 vaccination rollout in the United States is widely considered a success. However, there is still a great degree of confusion regarding the differences between the available formulations, their possible side effects, and the degree of protection they convey. 

The vaccines

Simple, actionable information is critical to provide clarity to the public. Here, we have included a brief roundup of the four most widely-used vaccines.

  • Pfizer – BioNTech

Pfizer – BionNTech was the first vaccine to be approved in the United States for emergency use. It is one of two mRNA-based (messenger Ribonucleic Acid) vaccines currently available. This vaccine requires two doses, given 21 days apart.

The Pfizer – BioNTech vaccine has already been massively deployed in the United States, Israel, Canada, and the European Union, among other countries.  It has also received WHO (World Health Organization) approval to participate in the COVAX initiative. 

It offers an efficacy of up to 91.3% in preventing infection. So far, it is also the only vaccine that has been proven effective in stopping the transmission of COVID-19, even among asymptomatic cases (Dagan et al., 2021).

Its main drawback is that it needs to be stored in ultra-cold temperatures of between -60 and -80 °C (-112 and -76 °F), increasing its final cost and making logistics more complicated.

  • Moderna

The Moderna vaccine was developed by the United States National Institute of Allergy and Infectious Diseases. It is now authorized for use in the United States, Canada, the United Kingdom, the European Union, and Singapore. However, it is not yet approved by the WHO.

Just like the Pfizer vaccine, this vaccine also uses mRNA technology to convey immunity. On the other hand, it can be stored and transported in standard medical refrigerators at temperatures of between 2 and 8 °C (36 to 46 °F)

This vaccine is given in two doses, four weeks apart.  In patients who have received both doses, these vaccines offer an efficacy of 94.1% in preventing symptomatic COVID-19 and a 100% efficacy in preventing hospitalizations (Oliver et al., 2021).

  • Johnson & Johnson

The Johnson & Johnson COVID-19 vaccine was the latest vaccine to receive emergency approval in the United States, although its use was paused shortly after. Janssen Pharmaceuticals in the Netherlands developed this vaccine. It uses viral vector technology based on a human adenovirus.

A prominent unique feature of this vaccine is that it requires a single dose. It is 66% effective in preventing symptomatic COVID-19 and 85% effective in preventing the severe form of the disease. Just like its peers, it has shown 100% efficacy in preventing COVID-19-related hospitalizations and deaths.

  • Astra Zeneca – Oxford

The Astra Zeneca – Oxford vaccine was approved in the United Kingdom and the European Union in December 2020. It has also received emergency approval from the WHO. However, it has not been approved in the United States. 

Just like the Johnson & Johnson vaccine, this vaccine was built using a viral vector. It is meant to be administered in 2 doses, between 4 and 12 weeks apart. This vaccine is 76% effective 22 days after the first dose. Following a second dose, the efficacy rises to 86.3% (Voysey et al., 2021).

VaccineTechnologyDosageApproved in the US?Approved by WHO / COVAX?EfficacyNotes
Pfizer-BioNTechmRNA2 Intramuscular (IM) shots, three weeks apartYES, for emergency and standard useYES, for emergency use91.3%, also prevents transmissionRequires ultra-cold storage
ModernamRNA2 IM shots, four weeks apartYES, for emergency useNO94.1% for symptomatic infections
Johnson & JohnsonA viral vector from human adenovirusSingle IM shotYES, for emergency useNO66% for symptomatic infections, 85% in preventing severe infectionTemporarily paused in the U.S.
AstraZeneca – Oxford UniversityA viral vector from a chimpanzee adenovirus2 IM shots, 4 weeks apartNOYES, for emergency use86.3% after the second doseIt was temporarily suspended in some EU countries.

What to expect after the vaccine

Despite the different technologies used, all these vaccines work by activating an immune response. Because of this, they all cause a similar cluster of common side effects. These have generally been described as similar to those of a mild cold and include:

  • Chills
  • Headaches
  • Fatigue or tiredness
  • Muscle aches (Meo et al., 2021)

Most of the time, these symptoms will disappear on their own after 1 or 2 days. Most people who receive any of the four vaccines described experience no noticeable side effects at all.

Rare side effects

A much smaller set of patients will experience fever within two days of the vaccine. 

For the Pfizer vaccine, approximately 6% of people experienced fever following the first dose. After the second dose, the likelihood of fever rises to 15%.  In the overwhelming majority of these cases, fever was only mild to moderate. Less than 0.3% of all vaccine recipients developed a fever of 39 °C (102 °F) or above (FDA & Pfizer, 2020).

In the case of the Moderna vaccine, less than 1% of people developed a fever after the first dose. After the second dose, 17% of patients experienced a mild fever of 38 °C (101 °F) or below.

The Moderna vaccine can also produce localized inflammation symptoms: approximately 14% of vaccine recipients developed redness, soreness, and mild swelling near the injection site. (FDA & Moderna, 2020). 

Extremely rare side effects

In extremely rare cases, some people have developed more dangerous adverse reactions to a COVID-19 vaccine. These incidents have received an unprecedented amount of media attention, although they affect less than 0.002% of people (or 20 out of 1 million people).


A handful of patients have developed an anaphylactic reaction immediately after receiving the COVID-19 vaccine. This reaction has been reported for the Pfizer, Moderna, and Astra Zeneca vaccines alike at the following rates:

  • For the Moderna vaccine, approximately 2 per 1 million doses have developed anaphylaxis a few minutes after receiving the injection.
  • For the Pfizer vaccine, the prevalence is approximately 11 cases per 1 million doses.
  • For the Astra Zeneca vaccine, 41 cases of anaphylaxis occurred from around 5 million vaccinations.

Because of this, the Center for Disease Control and Prevention (2021) has recommended that all patients remain under observation immediately after receiving the vaccine. 

For the general population, this waiting period should be 15 minutes. For patients with a history of anaphylaxis due to any reason or who have had an allergic reaction to a previous vaccine, the waiting period should be 30 minutes.

Blood clotting events

Finally, the Astra Zeneca and Johnson & Johnson vaccines have been linked to an increased risk of blood clot formation (Schultz et al., 2021).

In the case of the Johnson & Johnson vaccines, six patients out of over 7 million developed a severe form of thrombosis. All six cases happened in women aged 18 to 48. Because of this, the FDA decided to pause the administration of this vaccine temporarily.

Meanwhile, the Astra Zeneca vaccine has also been linked to extremely rare events of deep vein thrombosis and other blood clotting disorders. So far, the European Medicines Agency has confirmed this occurred to 222 patients out of 34 million vaccine recipients. 

Some countries decided to suspend the administration of the Astra Zeneca vaccine temporarily. However, in most cases, its authorization was resumed, as the risk of developing blood clots from a COVID-19 infection is at least ten times higher (Mahase, 2021).

Precautions and Management for Adverse Reactions

The overwhelming majority of side effects linked to vaccination are not dangerous and resolve themselves within 48 hours. If symptoms such as fever or muscle pain become too hard to bear, the CDC recommends patients to take over-the-counter medication such as ibuprofen (Advil©), Aspirin©, or acetaminophen (Tylenol©). 

Meanwhile, because anaphylaxis is an immediate reaction, the use of the 15-minute observation period offers a low-cost, non-invasive precaution that can be easily implemented around the world. 

Finally, the United Kingdom’s Medicines & Healthcare Products Regulatory Agency (2021) has published a list of symptoms that should prompt people to seek immediate medical attention if experienced within 4 days between receiving the vaccine. These symptoms include:

  • Blurred vision
  • Confusion
  • Difficulty speaking
  • A blue or purple rash, similar to that of bruises, appearing under the skin

Conclusion: Knowledge and Calm Will See Us Out of the Tunnel

The current COVID-19 vaccine rollout has received an unusual amount of scrutiny. Thus, many people are hesitant to receive a vaccine or continue delaying their appointments in hopes of receiving a “better” brand.

An in-depth look at the different vaccines currently available reveals that severe adverse reactions are extremely rare and are greatly surpassed by the risks of COVID-19. Although there are minor differences in the efficacy between each vaccine, they all offer 100% protection against severe COVID-19 symptoms or death from COVID-19 once all required doses have been completed. 

Ultimately, all vaccines will help in acquiring herd immunity. Hopefully, soon, the 2021 vaccination rollout will enter the history books as one of humankind’s highest scientific cooperation achievements.


Center for Disease Control and Prevention (2021) Interim Clinical Considerations for the use of COVID-19 Vaccines Currently Authorized in the United States. Accessed online on April 20th, 2021 at https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html 

Dagan, N., Barda, N., Kepten, E., Miron, O., Perchik, S., Katz, M. A., Hernán, M. A., Lipsitch, M., Reis, B., & Balicer, R. D. (2021). BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. The New England journal of medicine, 384(15), 1412–1423. https://doi.org/10.1056/NEJMoa2101765

Food and Drug Administration & Moderna TX. (2021). FDA Briefing Document: Pfizer-BioNTech COVID-19 Vaccine. Accessed online on April 21st, 2021 at https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine

Food and Drug Administration & Pfizer – BioNTech. (2021). FDA Briefing Document: Moderna COVID-19 Vaccine. Accessed online on April 21st, 2021 at https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine

Janssen Vaccines. (2020). A randomized, double-blind, placebo-controlled phase 3 study to assess the efficacy and safety of Ad26. COV2. S for the prevention of SARS-CoV-2-mediated COVID-19 in adults aged 18 years and older.

Mahase E. (2021) Covid-19: AstraZeneca vaccine is not linked to increased risk of blood clots, finds European Medicine Agency. British Medical Journal. 2021; 372 :n774 doi:10.1136/bmj.n774 

Meo, S. A., Bukhari, I. A., Akram, J., Meo, A. S., & Klonoff, D. C. (2021). COVID-19 vaccines: comparison of biological, pharmacological characteristics and adverse effects of Pfizer/BioNTech and Moderna Vaccines. European review for medical and pharmacological sciences, 25(3), 1663–1669. https://doi.org/10.26355/eurrev_202102_24877

Medicines & Healthcare Products Regulatory Agency (2021) Coronavirus vaccine adverse reactions – Yellow Card Reporting Accessed online on April 20th, 2021 at https://www.gov.uk/government/publications/coronavirus-covid-19-vaccine-adverse-reactions/coronavirus-vaccine-summary-of-yellow-card-reporting

Oliver S, Gargano J, Marin M, et al. (2020). The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Moderna COVID-19 Vaccine — United States, December 2020. MMWR Morb Mortal Wkly Rep 2021;69:1653-1656. DOI: http://dx.doi.org/10.15585/mmwr.mm695152e1

Schultz, N. H., Sørvoll, I. H., Michelsen, A. E., Munthe, L. A., Lund-Johansen, F., Ahlen, M. T., … & Holme, P. A. (2021). Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. New England Journal of Medicine.

Voysey, M., Clemens, S. A. C., Madhi, S. A., Weckx, L. Y., Folegatti, P. M., Aley, P. K., … & Bird, O. (2021). Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomized trials. The Lancet, 397(10277), 881-891

Jennifer Billings is the Medical Editor at National Coronavirus Hotline(NCH). She is an Integrated medical doctor who has been published on NCH Blog, Medium.com and is a regular contributor at MedCity News, Physician Family, and Psychology Today.