IVS logo - links back to home page

What We Know So Far

COVID-19 Vaccines

Background | Clinical Trial Data | Post-Authorization Surveillance| Sources

updated 5/19/22

There are three different COVID-19 vaccines currently available in the United States (US). Below we describe these vaccines and summarize the available data on study participation, efficacy, and safety.

To find COVID-19 vaccines in your area, go to Vaccines.gov.

Background Information

Authorization
The US Food & Drug Administration (FDA) has issued the following Emergency Use Authorizations (EUA) and approvals for vaccines against Coronavirus Disease 2019 (COVID-19). Timeline of and links to FDA announcements:

  • March 2022
    • A second booster dose of Pfizer-BioNTech or Moderna vaccine were given EUA for adults 50 years and older and certain immunocompromised individuals.
  • January 2022
  • November 2021
  • October 2021
  • September 2021
  • August 2021
    • The Pfizer-BioNTech vaccine was fully approved (trade name: Comirnaty®) for individuals 16 years of age and older (the vaccine will continue to be available under EUA for adolescents 12 to 15 years of age).
  • May 2021
  • February 2021
  • December 2020
    • The vaccine developed and manufactured by Pfizer-BioNTech was given EUA for individuals 16 years and older.
    • The vaccine by Moderna was given EUA for adults 18 years and older.

Recommendations
The US Centers for Disease Control and Prevention (CDC), per the recommendations of its independent advisory committee, the Advisory Committee on Immunization Practices (ACIP) recommends COVID-19 vaccination for everyone 5 years of age and older:

  • Primary Series
    • All children and adolescents ages 5 to 17 without contraindications should receive two doses of Pfizer-BioNTech vaccine administered 3-8 weeks apart.
    • All adults (18+ years) without contraindications should receive a primary COVID-19 vaccine series comprising either: two doses of Pfizer-BioNTech vaccine administered 3-8 weeks apart, two doses of Moderna vaccine administered 4 weeks apart, or one dose of J&J vaccine.
      • mRNA (Pfizer-BioNTech and Moderna) COVID-19 vaccines are preferred to J&J.
      • An 8-week interval may be optimal for some people, espeically for males ages 12 to 39 years, to further decrease the small risk of myocarditis.
      • A shorter (3-4 week) interval remains the recommended interval for:
        • all persons who have moderately to severely compromised immune systems
        • adults ages 65 years and older
        • others who need rapid protection due to increased concern about community transmission or risk of severe disease
    • All persons (5+ years) who received two doses of Pfizer-BioNTech or Moderna vaccine who have moderately to severely compromised immune systems should receive a third primary series dose a minimum of 28 days after the second dose.
    • All adults (18+ years) who have moderately to severely compromised immune systems who received J&J vaccine should receive an additional dose with an mRNA vaccine at least 4 weeks after second dose.
  • Boosters
    • All adults (18+ years) who received one dose of J&J vaccine should receive a booster dose (of whichever COVID-19 vaccine they prefer) a minimum of 2 months after the initial dose.
    • All adults (18+ years) who received a primary series of Pfizer-BioNTech or Moderna vaccine should receive a booster dose (of whichever COVID-19 vaccine they prefer) a minimum of 5 months after the previous dose.
    • Children and adolescents (5-17 years) who received a primary series of Pfizer-BioNTech COVID-19 vaccine should receive a booster dose of Pfizer-BioNTech COVID-19 vaccine a minimum of 5 months after the previous dose.
    • All persons (5+ years) who have moderately to severely compromised immune systems who received a primary series of Pfizer-BioNTech or Moderna vaccine should receive a booster dose a minimum of 3 months after the third mRNA primary series dose.
    • Pfizer-BioNTech or Moderna vaccine should receive a booster dose a minimum of 3 months after the third mRNA primary series dose.
    • All adults (18+ years) who have moderately to severely compromised immune systems who received J&J vaccine should receive a mRNA booster dose a minimum of 2 months after the additional primary series dose.
    • Adolescents (12-17 years) who have moderately to severely compromised immune systems may receive a second booster dose of Pfizer-BioNTech COVID-19 vaccine a minimum of 4 months after the previous booster dose.
    • Adults (18+ years) who have moderately to severely compromised immune systems may receive a second mRNA booster dose a minimum of 4 months after the previous booster dose.
    • Adults 50+ years old may receive a second mRNA booster dose a minimum of 4 months after the previous booster dose.
    • Adults (18+ years) who received J&J vaccine as both their primary series and booster dose may receive a second booster dose (of an mRNA vaccine) a minimum of 4 months after the previous booster dose.

Vaccine Types
 Both the Pfizer-BioNTech and Moderna vaccines are messenger RNA (mRNA) vaccines, a new type of vaccine. The technology behind the mRNA vaccines has been studied and developed for years by organizations such as the Coalition for Epidemic Preparedness Innovations (CEPI), especially their potential use during epidemics and pandemics. This prior work allowed mRNA vaccines specific to COVID-19 to be created very quickly once the genome of the virus was determined.

The injected mRNA uses our own cells to produce the spike protein from the virus, stimulating an antibody response that provides protection against natural infection. mRNA does not enter the nucleus of cells and is broken down quickly.

The J&J vaccine is a viral vector vaccine (specifically, a non-replicating adenovirus type 26-vectored vaccine). Viral vector technology has been well studied and used for other vaccines such as Ebola. In viral vector vaccines, a modified virus is used as a vector to deliver a specific gene to our cells that instructs them to produce the target protein (the COVID-19 spike protein), stimulating antibody response and protection against disease. This is not considered a live vaccine. Although the vector delivers information to human cells, the virus does not replicate and cannot cause an infection.

None of the vaccines can cause COVID-19 infection or affect DNA.

Dosing Schedule and Amounts
 Two doses of the Pfizer-BioNTech vaccine are recommended to be administered three weeks apart, and doses of the Moderna vaccine are recommended to be administered four weeks apart. However, there is no maximum interval between the first and second dose for either vaccine, so delays between doses due to the need for allergist/immunologist evaluation (see Contraindications and Precautions section) or supply constraints should not interfere with administration of the second dose once ready. CDC also recommends that moderately to severely immunocompromised people receive a third dose of the same mRNA vaccine at least four weeks after their second dose.

CDC recommends a single booster dose at least 5 months after a second dose of mRNA COVID-19 vaccine for all adults (18+ years), and a single booster dose at least 5 months after a second dose of Pfizer-BioNTech mRNA COVID-19 vaccine for all adolescents (12-17 years). CDC recommends a single booster dose at least 2 months after an initial J&J COVID-19 vaccine for all adults (18+ years). CDC also recommends additional doses for moderately to severely immunocompromised people; see the Recommendations section above for more details.

All vaccine recipients should be observed for at least 15 minutes after vaccination because of the possibility of fainting or potential allergic reactions (see Anaphylaxis/Hypersensitivity Reactions section).

Each dose of Pfizer vaccine for adults (including primary series and booster doses) consists of 0.3mL of liquid containing 30 micrograms of mRNA; each dose of Pfizer vaccine for children consists of 0.2mL of liquid containing 10 micrograms of mRNA. Each primary series dose of Moderna vaccine for adults consists of 0.5mL of liquid containing 100 micrograms of mRNA; each booster dose of Moderna vaccine for adults consists of 0.25mL of liquid containing 50 micrograms of mRNA. Each dose of J&J vaccine for adults (including primary series and booster doses) consists of 0.5mL of liquid. links to CDC and CDC COVID-19.

Accelerated Timeline
Many factors contributed to the unprecedentedly rapid development, testing, and authorization of COVID-19 vaccine candidates. Some of these factors include combining clinical phases, rapid accumulation of assessable cases due to the high rate of disease and reduction of financial risk to manufacturers.  The FDA maintains rigorous standards for vaccine efficacy and safety for emergency use authorization (EUA) and for the final complete approval for these vaccine which is expected later in 2021. The risk of moving at a rapid pace for EUA has been mainly financial; if a vaccine candidate is found not to meet safety and efficacy standards at any point, it is discontinued and the money invested to conduct these trials and create the manufacturing capacity for the vaccine ahead of time is lost. This financial risk has largely been taken on by governments and manufacturers. Supporting the development of multiple vaccine candidate increases the chances that some vaccine candidates will prove to be very safe and effective and will be manufactured at scale in time to make a difference in the fight against this ongoing pandemic.

Contraindications and Precautions
A history of immediate allergic reaction of any severity to a COVID-19 vaccine, or to any component of a COVID-19 vaccine is a contraindication to receive additional doses of the vaccine. Persons with known allergic reactions to polyethylene glycol (PEG)should not receive the mRNA vaccines. Polysorbate, which is contained in the Janssen vaccine has the potential for cross-reactive hypersensitivity with PEG.  The components for COVID-19 vaccines are listed on the CDC website as well as on our COVID-19 Components page. 

Persons who had allergic reactions that were not severe may be able to receive the a COVID-19 vaccine after evaluation by an allergist-immunologist. Those with a contraindication to mRNA COVID-19 vaccines automatically have a precaution to Janssen COVID-19 vaccine, and vice versa. Persons who received one mRNA COVID-19 dose but are contraindicated to receive the second dose may receive Janssen COVID-19 vaccine at least 28 days after the mRNA vaccination, under the supervision of a health care provider experienced in the management of severe allergic reactions.

A history of severe allergic reaction (eg, anaphylaxis) to any other vaccine or injectable therapy is a precaution to COVID-19 vaccination; persons with such a history may be vaccinated but should be counseled about the potential risks before and observed for 30 minutes after vaccination. Moderate or severe acute illness is also a precaution to COVID-19 vaccination; such persons should be counseled about the potential risks and observed for 15 minutes after vaccine administration.

Those with a history of mild allergic reaction to a vaccine or a history of allergic reactions (including severe allergic reactions) unrelated to vaccines, PEG, and polysorbate may proceed with COVID-19 vaccination. There are currently no other contraindications or precautions to COVID-19 vaccination including immunocompromising conditions, pregnancy, and lactation. These recommendations may change as further information becomes available and will be updated on the CDC website accordingly.

Considerations for Pregnancy and Breastfeeding
Initially, only limited data are available for pregnant and breastfeeding womena as they were excluded from clinical trials. Some vaccinated women have become pregnant and their pregnancies are being monitored. The manufacturers have conducted Developmental and Reproductive Toxicity (DART) studies in animals and have identified no safety signals.

Early data on the efficacy of mRNA COVID-19 vaccines during pregnancy are promising. Immune responses among pregnant women appear similar to non-pregnant women, and vaccine-generated antibodies transferred to unborn infants via the umbilical cord and recently born infants via breastmilk. Effectiveness of the Pfizer-BioNTech vaccine among pregnant women appears high and comparable to the general population.

Early data on the safety of mRNA COVID-19 vaccines during pregnancy are reassuring; no obvious signals have arisen in safety monitoring for pregnant women or their babies, and active case-control surveillance found no link between vaccination and spontaneous abortion. No vaccines, including COVID-19 vaccines, have been shown to affect fertility in women or men.

The available COVID-19 vaccines are not live vaccines and the theoretical risks are minimal. Thus, the American College of Obstetricians and Gynecologists (ACOG) has recommended that all pregnant and lactating individuals be vaccinated against COVID-19. Pregnancy registries have been established to monitor the outcomes of women pregnant at the time of vaccination.

Vaccine Safety Monitoring and Injury Compensation
There are many systems set up to monitor the safety of the COVID-19 vaccines. Upon vaccinating, please consider signing up for V-safe, a CDC-run smartphone-based tool that uses text messaging and web surveys to provide personalized health check-ins. If you do experience an adverse event after vaccination, please make sure you or your provider report it to the Vaccine Adverse Reporting System (VAERS). In the unlikely event you experience a serious injury from a COVID-19 vaccine, you may be considered for benefits through the Countermeasures Injury Compensation Program (CICP).

Clinical Trial Data

The efficacy and safety data from the Pfizer-BioNTech vaccine's phase III clinical trial was published in the New England Journal of Medicine (NEJM) on December 10, 2020. It was also made available via the Briefing Document FDA created for its independent advisory committee, the Vaccines and Related Biological Products Advisory Committee (VRBPAC). The efficacy and safety data from the expansion of Pfizer-BioNTech vaccine's phase III clinical trial for adolescents 12 to 15 years of age was published in the New England Journal of Medicine (NEJM) on July 15, 2021. The efficacy and safety data from the Pfizer-BioNTech vaccine's phase II/III clinical trial for children 5 to 11 years of age was published in the NEJM on November 9, 2021, and was also made available via the VRBPAC Briefing Document.

The efficacy and safety data from the Moderna vaccine's phase III clinical trial were published in the NEJM on December 30, 2021 and more information was made available via the VRBPAC Briefing Document.

The efficacy and safety data from the Janssen vaccine's phase III clinical trial were published in the NEJM on June 10, 2021 and more information was made available via the VRBPAC Briefing Document.

Study Participation
More than 43,000 volunteers participated in the Pfizer-BioNTech phase III clinical trial; about half were randomly assigned to receive the vaccine (the other half received saline placebo). Approximately three-quarters of participants were in the United States; 15% in Argentina, 6% in Brazil and 2% in South Africa. About half of participants were female. The minimum age was 16 years and the median age was 52 years, with 21% over 65 years.  About one third of participants were obese, and about one fifth had at least one coexisting medical condition. Those with a medical history of COVID-19 or severe allergic reaction to a vaccine component, immunosuppression either from a condition or therapy, and pregnant/breastfeeding women were excluded from this study. Additional studies are planned to evaluate these groups. Those with stable chronic medical conditions (including HIV and hepatitis) remained eligible for participation. Additional studies are planned to evaluate these groups. Those with stable chronic medical conditions (including HIV and hepatitis) remained eligible for participation. This trial was later expanded to include a subset of 2260 US adolescents 12-15 years of age; about half were randomly assigned to receive the vaccine (the other half received saline placebo). About 50% were female; 86% were white, 5% were Black, 6% were Asian; and 12% were Latinx. Pfizer-BioNTech then conducted a phase II/III clinical trial among 2268 children 5-11 years of age; about two thirds were randomly assigned to receive the vaccine (the other third received saline placebo). About 47% were female; 79% were white, 6% were Black, 6% were Asian; and 21% were Latinx. Another 2379 children were later enrolled into a supplemental safety expansion group, all receiving the vaccine. Trials among adolescents and children were able to assess immunogenicity, efficacy, and common side effects, but were insufficiently large to assess risks of uncommon or rare adverse events.

Study participants by Race/Ethnicity  
Pfizer* Moderna Janssen*
White 83% 79% 62%
Black 9% 10% 17%
Asian 4% 5% 4%
Latinx** 28% 20% 45%
Native American 0.5% 0.8% 3.5%
* Percentages reflect global study population
**Categories not mutually exclusive		  

More than 30,000 volunteers participated in the Moderna phase III clinical trial, about half were randomly assigned to receive the vaccine (the other half received saline placebo). The trial was conducted in the US. About half of participants were female. The median age was 53 years, with 25% over 65 years. More than one fifth of participant had at least one preexisting high risk medical condition. Those with a known history of COVID-19 or severe allergic reaction to a vaccine component, immunosuppression either from a condition or therapy, pregnant/breastfeeding women, and children under 18 years old were excluded from this study. Those with stable chronic medical conditions remained eligible for participation.

More than 39,000 volunteers participated in the Janssen phase III clinical trial; about half were randomly assigned to receive the vaccine (the other half received placebo). Almost half of participants were in the United States; 17% were in Brazil, 13% in South Africa, and the remaining 23% in one of five Latin American countries (Columbia, Argentina, Peru, Chile, and Mexico). About 45% of participants were female. The median age was 53 years, with 20% over older than 65 years. Nearly 40% had at least one preexisting medical condition associated with increased risk of severe COVID-19. Pregnant women, children under 18 years old, those who had received another COVID-19 vaccine, and those who had recently received certain COVID-19 treatments were excluded from this study.

Efficacy Data
Starting one week after the second dose, the Pfizer-BioNTech vaccine prevented COVID-19 with 95% efficacy (95%CI: 90.3-97.6) among participants older than 16 years of age without prior evidence of natural infection. Efficacy remained at least 94% when including participants with prior infection. Efficacy was consistent across demographic subgroups. One severe case of COVID-19 occurred in the vaccine group compared to 4 in the placebo group. Among the subset of adolescents 12-15 years of age, the Pfizer-BioNTech vaccine produced a greater immune response than among young adults (16-25 years of age) and prevented COVID-19 with 100% efficacy. Among children 5-11 years of age, the Pfizer-BioNTech vaccine prevented COVID-19 with 90.7% efficacy (95%CI: 67.7%-98.3%).

Starting two weeks after the second dose, the Moderna vaccine prevented COVID-19 with 94.5% efficacy (95%CI: 86.5%-97.8%) among participants without prior evidence of natural infection. Efficacy remained at least 93% when including participants with prior infection. Efficacy was consistent across demographic subgroups. All 11 severe cases of COVID-19 occurred in the placebo group.

Starting two weeks after vaccination, the Janssen vaccine prevented moderate to severe COVID-19 with 67% efficacy (95%CI: 59.0-73.4). Efficacy was consistent across demographic subgroups (e.g., age, comorbidity, race, ethnicity). As of February 5, 2021, 7 COVID-19 related deaths occurred in the placebo group compared to 0 in the vaccine group.

Safety Data
Common side effects from Pfizer-BioNTech vaccinations among participants older than 16 years included: injection site reactions (e.g., pain, redness, swelling) (84%), fatigue (63%), headache (55%), muscle pain (38%), chills (32%), joint pain (24%), and fever (14%). The vast majority of these were mild to moderate, resolving within a couple of days after onset. Systemic effects were more common and severe after the second dose compared to the first, with the most frequent "severe" side effects of the second dose being fatigue (5%), headache (3%), chills (2%), and muscle pain (2%). Most of these effects were less common and milder among older adults compared to younger adults.

Among adverse events of special interest (AESIs) which could possibly be related to vaccination, lymphadenopathy (axillary swelling and tenderness of the vaccination arm) was reported in 64 vaccine recipients (0.3%) compared to only 6 (<0.1%) in the placebo group, lasting for 10 days on average. Bell’s palsy was reported in four vaccine recipients (<0.1%) and none in placebo recipients. The observed rate is consistent with the expected background rate in the general population, and there was no time clustering to suggest a causal relationship. No other notable patterns that would suggest a causal relationship were noted by the FDA. This includes deaths, of which 2 were reported among vaccine recipients and 4 among placebo recipients, numbers consistent with the expected background rate in the general population for these age groups.

Rates of common side effects among adolescents 12-15 years of age were similar to rates among young adults (16-25 years of age), and no vaccine-related serious adverse events occurred among adolescents 12-15 years of age. Among children 5-11 years of age, some injection site reactions (e.g., redness, swelling) were higher than among young adults. However, rates of systemic reactions (e.g., fever) were lower among children than young adults, reactogenicity was mostly mild to moderate and quickly resolving, and no vaccine-related serious adverse events occurred.

Common side effects from Moderna vaccinations included: injection site pain (92%), fatigue (69%), headache (63%), muscle pain (60%), joint pain (45%), chills (43%), and fever (15%). The vast majority of these were mild to moderate. Systemic effects were more common and severe after the second dose compared to the first, with the most frequent "severe" side effects of the second dose being fatigue (10%), headache (6%), muscle pain (9%), joint pain (5%), and chills (1%). However, most of these effects were less common and milder among older adults compared to younger adults. Among adverse events of special interest (AESIs) which could possibly be related to vaccination, lymphadenopathy was reported in 173 vaccine recipients (1.1%) compared to 95 (0.6%) in the placebo group. Bell’s palsy was reported by three vaccine recipients and one placebo recipient; the low frequency was consistent with the expected background rate in the general population. Hypersensitivity wase reported in 1.5% of vaccine recipients compared to 1.1% of placebo recipients; however, no episodes of anaphylaxis or severe hypersensitivity had close temporal relation to the vaccine. Three vaccine recipients with dermal fillers reported swelling at the site of the fillers after vaccination; two of these were reported as Serious Adverse Events (SAEs), but all resolved over time. The mechanism behind this reaction is not yet known. No other notable patterns that would suggest a causal relationship were noted by the FDA. This includes deaths, of which 6 were reported among vaccine recipients and 7 among placebo recipients, numbers consistent with the expected background rate in the general population for these age groups.

Common side effects from Janssen vaccinations included: injection site pain (49%), headache (39%), fatigue (38%), muscle pain (33%), nausea (14%), and fever (9%). The vast majority of these were mild to moderate, resolving within a couple of days after onset. Adverse events with numerical imbalances between groups included: urticaria (hives), which was reported in 5 vaccine recipients compared to 1 in the placebo group; thromboembolic events, which were reported in 15 vaccine recipients compared to 10 in the placebo group; and tinnitus, which was reported in 6 vaccine recipients compared to none in the placebo group. These data are insufficient to determine causality. No other notable patterns that would suggest a causal relationship were noted by the FDA. This includes deaths; 5 were reported among vaccine recipients and 20 among placebo recipients as of February 5, 2021.

Conclusions from Clinical Trial Data
Both the Pfizer-BioNTech and Moderna vaccines are two-dose mRNA vaccines that are highly efficacious against COVID-19 (~90-95%); the Janssen vaccine is a one-dose viral vector vaccine that is less efficacious but still protective against moderate to severe disease (~67%). Mild to moderate local and systemic side effects are common and should be expected with both mRNA vaccines; systemic side effects are more frequent following the second dose, and most local and systemic side effects are less common among older adults than among children, adolescents, and young adults. Mild to moderate local and systemic side effects after the Janssen vaccine are less common than after the mRNA vaccines but should still be expected. Other than hypersensitivity reactions discussed below, no associations with other adverse events of special interest were found with these vaccines. Preliminary data have not revealed any safety signals among pregnant persons who received mRNA COVID-19 vaccines.

Post-Authorization Surveillance

Post-authorization surveillance monitors for and evaluates real-world effectiveness and safety signals that arise after a vaccine is approved for use in the general population.  To date, data from post-authorization surveillance of COVID-19 vaccines appear reassuring.

Real-World Effectiveness
Authorized mRNA vaccines are effectively prevent COVID-19 infections, symptoms, hospitalization and death. In a prospective cohort of nearly 4,000 health care personnel tested weekly for 13 weeks through March 2021, full immunization (≥14 days after dose 2) was 90% effective against infection (95%CI: 68-97), and partial immunization (≥14 days after dose 1 but before dose 2) was 80% effective against infection (95%CI: 59-90), regardless of symptoms.

In a multisite test-negative study among health care personnel through March 2021, full immunization was 94% effective against symptomatic disease, and partial immunization was 82% effective against symptomatic disease.

In a retrospective case-control study of more than 136,000 individuals in five states between December 2020 and April 2021, at least one dose of Pfizer-BioNTech or Moderna vaccine was 86% and 93% effective against infection, respectively, and both vaccines were 100% effective in preventing COVID-19-associated intensive care unit (ICU) admission.

In a case-control analysis of 3,689 US adults without immunocompromising conditions hospitalized between March and August 2021, effectiveness against hospitalization was higher for Moderna (93%) and Pfizer-BioNTech (88%) vaccines compared to Janssen vaccine (71%). The effectiveness of J&J vaccine against COVID-19 infection and hospitalization is substantially lower than the effectiveness of either mRNA vaccine, though still impactful.

The effectiveness of COVID-19 vaccines against infection slowly declines over time, and COVID-19 vaccines are also somewhat less effective against infection with the Delta and Omicron variants compared to the original strain. However, COVID-19 vaccines still greatly reduce the risk of infection and remain highly effective at preventing severe disease and death.

Booster Doses
Initial data show a 96% relative efficacy of the Pfizer-BioNTech booster dose. An analysis of 87,904 adult hospitalizations from 259 hospitals in 10 states between August 2021 and January 2022 found that receiving a booster dose was 94% effective against hospitalization with illness from the Delta variant and 90% effective against hospitalization with illness from the Omicron variant. Side effects following mRNA booster doses have so far been reported less frequently than after the second dose of the primary series.

Deaths Among Older Adult Residents of Long-Term Care Facilities
Deaths following COVID-19 vaccination in older adults dwelling in long-term care facilities have been reported. Analyses examining the cause of death and comparing with expected background rates of death in this population do not suggest a causal association.

Anaphylaxis/Hypersensitivity Reactions
Higher than expected rates of anaphylaxis following the Pfizer-BioNTech (~4.7 cases per million doses) and Moderna (~2.5 cases per million doses) COVID vaccines have been identified as compared to ~1 case per million doses for most other vaccines. Investigations are working to identify the cause. Some allergists have speculated that polyethelene glycol (PEG), a component in both approved vaccines, may be responsible. PEG can be found in osmotic laxatives and oral bowel preparations for colonoscopy procedures, among other medications. Cross-reactive hypersensitivity between PEG and polysorbates may also occur. Polysorbates can be found in many licensed vaccines, as well as some injectable drugs (e.g., corticosteroids), biological agents and monoclonal antibodies. The CDC provides guidance for screening to detect individuals who might be at risk, managing allergic reactions, and recommendations for those who experience an allergic reaction after receiving a COVID-19 vaccine or have a history of allergic reactions. Personnel at all sites administering these (and other) vaccines should be prepared to promptly treat individuals who develop allergic reactions. All vaccine recipients should be observed for at least 15 minutes after vaccination to safeguard against potential allergic reactions; persons with a history of anaphylaxis should be observed for at least 30 minutes.

Myocarditis/Pericarditis
mRNA COVID-19 vaccination has been associated with rare cases of Myocarditis and Pericarditis, mostly among young males after the second dose. Of more than 2.5 million persons receiving the Pfizer-BioNTech vaccine in Israel, 54 cases of myocarditis were identified, most of which were mild or moderate in severity; the rate of myocarditis was highest among males 16-29 years of age (11 per 100,000 vaccinated persons). Of more than 400,000 adolescents 12-15 years of age receiving the Pfizer-BioNTech vaccine in Israel, 13 cases of myocarditis were identified, all of which were mild in severity; the rate of myocarditis after the second dose was 8 per 100,000 adolescents 12-15 years of age. Data from the US Vaccine Safety Datalink (VSD) as of October 23, 2021, estimated a rate of 11 per 100,000 second doses of Pfizer-BioNTech vaccine among adolescent males 12-15 years of age, and suggested double the risk of myocarditis after Moderna versus Pfizer-BioNTech vaccine. link to Myocarditis/pericarditis and mRNA COVID-19 Vaccines page

Thrombosis with Thrombocytopenia Syndrome (TTS)
J&J vaccination has been associated with very rare cases of Thrombosis with Thrombocytopenia Syndrome (TTS). TTS is a serious condition involving blood clots with low platelets and has mostly occurred in  women 30-49 years of age. The FDA and CDC paused J&J vaccination on April 13, 2021, after 6 cases of TTS were reported to the US passive safety monitoring system VAERS, so that these cases could be investigated further. The pause was ultimately lifted on April 23, 2021, by which time the total cases reported to VAERS had grown to 15, as the ACIP determined that the benefits of vaccination outweighed the risks due to the rarity of TTS and the risks of COVID-19. However, young women may wish to choose an mRNA COVID-19 vaccine to avoid the small risk of TTS. As of December 16, 2021, 54 cases of TTS (37 in females and 17 in males) and 8 TTS-related deaths have been confirmed following J&J vaccination (out of 14.1 million doses administered).

Guillain-Barré Syndrome (GBS)
J&J vaccination may also be associated with very rare cases of Guillain-Barré Syndrome (GBS). Data from the VSD, as of November 13, 2021, estimated an unadjusted incidence rate of 34.6 confirmed cases of GBS per 100,000 person-years within 21 days after J&J vaccination (95%CI: 15.8-65.7), significantly higher than the background rate, and an adjusted risk ratio (versus 22-42 days after vaccination) of 6.03 (95% CI: 0.79-147.79).

Other Adverse Events Identified in Post-Authorization Surveillance
Other adverse events identified in an evaluation of data from over 2.4 million persons receiving the Pfizer-BioNTech vaccine in Israel included lymphadenopathy (with an excess risk of 78.4 events per 100,000 persons), herpes zoster (with an excess risk of 15.8 events per 100,000 persons), and appendicitis (with an excess risk of 5.0 events per 100,000 persons).

Sources

Publications Analyzing Phase III Clinical Trial Data
• Pfizer-BioNTech
• Moderna
• Janssen

FDA
• Emergency Use Authorization Main Page
• EUA for Vaccines Explained
• Pfizer-BioNTech Briefing
• Moderna Briefing
• Janssen Briefing
• FDA Approves First COVID-19 Vaccine
• FDA Review of Efficacy and Safety of Pfizer-BioNTech COVID-19 Vaccine Emergency Use Authorization Request
• FDA Review of Efficacy and Safety of Moderna COVID-19 Vaccine Emergency Use Authorization Request
• FDA Review of Efficacy and Safety of Janssen COVID-19 Vaccine Emergency Use Authorization Request
• Pfizer-BioNTech Fact Sheets and Additional Information
• Moderna Fact Sheets and Additional Information
• Janssen Fact Sheets and Additional Information

CDC
• ACIP COVID-19 Recommendations
• Understanding mRNA COVID-19 Vaccines
• Understanding and Explaining Viral Vector COVID-19 Vaccines
• Ensuring the Safety of COVID-19 Vaccines in the US
• Interim Clinical Considerations for Use of mRNA COVID-19 Vaccines Currently Authorized in the US
• COVID-19 Vaccines and Severe Allergic Reactions
• Preparing for the Potential Management of Anaphylaxis at COVID-19 Vaccination Sites
• Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020
• First Month of COVID-19 Vaccine Safety Monitoring — United States, December 14, 2020–January 13, 2021
• Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers — Eight U.S. Locations, December 2020–March 2021
• COVID-19 Vaccines for Moderately to Severely Immunocompromised People
• Delta Variant: What We Know About the Science

ACOG
• Vaccinating Pregnant and Lactating Patients Against COVID-19 – Practice Advisory

The Society for Maternal and Fetal Medicine
• SMFM Statement: SARS-CoV-2 Vaccination in Pregnancy

Johns Hopkins Coronavirus Resource Center
• JH Coronavirus Resource Center Main Page
• Vaccine Development Timeline

Coalition for Epidemic Preparedness Innovations (CEPI)
• CEPI Main Page
• Vaccine Safety Q & A

ClinicalTrials.Gov
• Pfizer-BioNTech
• Moderna
• Janssen
 

The information on this page was last updated on May 19, 20222 | © 2022 Institute for Vaccine Safety