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What We Know So Far

COVID-19 Vaccines

Background | Clinical Trial Data | Post-Licensure Safety Surveillance | Sources

updated 02/20/21

The United States (US) Food & Drug Administration (FDA) has issued Emergency Use Authorizations (EUA) for two vaccines against Coronavirus Disease 2019 (COVID-19): one developed and manufactured by Pfizer-BioNTech and one by Moderna. Below we describe these vaccines, explain how they were made so fast, and summarize the available data on study participation, efficacy and safety.

Background Information

Availability
The US Centers for Disease Control and Prevention (CDC), per the recommendations of its independent advisory committee, the Advisory Committee on Immunization Practices (ACIP), has established phases for vaccine allocation, based on available science and ethical considerations. Phase 1a includes health care personnel and long-term care facility residents. Phase 1b includes frontline essential workers and those at least 75 years old. Phase 1c includes other non-frontline essential workers, those at least 65 years old, and those at least 16 years old with high-risk medical conditions. Phase 2 includes everyone who was not included in Phase 1 who is at least 16 years old.

Dosing Schedule
Both vaccines require two doses. 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. All vaccine recipients should be observed for at least 15 minutes after vaccination because of the possibility of fainting or potential allergic reactions (seeAnaphylaxis/Hypersensitivity Reactions section).

mRNA Vaccines
Both vaccines are messenger RNA (mRNA) vaccines, a new type of vaccine. The technology behind the mRNA vaccines has been studied and developed for years, including 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 stimulate antibody response that provides protection against natural infection. mRNA does not enter the nucleus of cells and is broken down quickly. Organizations such as the Coalition for Epidemic Preparedness Innovations (CEPI) have been studying and developing these technologies for years.

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.  These actions did not compromise the rigorous standards for vaccine efficacy and safety. The risk of moving at this rapid pace is mainly financial; if a vaccine candidate is found not to meet safety and efficacy standards at any point in the clinical trials, 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, any component of these vaccines (including polyethylene glycol [PEG]), or polysorbate (due to potential cross-reactive hypersensitivity with PEG) is a contrainhdication to administering the vaccine. Those who had allergic reactions that were not severe may be able to receive the vaccine after evaluation by an allergist-immunologist. The components for both COVID-19 vaccines are listed on the CDC website as well as on our COVID-19 Components page

A history of severe allergic reaction (e.g., 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.

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 are contraindications or precautions to 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 Pregnant and Breastfeeding Women
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 major safety signals.

The available COVID-19 vaccines are not live vaccines and the theoretical risks are minimal. The American College of Obstetricians and Gynecologists (ACOG), the Society of Maternal and Fetal Medicine, and the ACIP have recommended that COVID-19 vaccines should not be withheld from pregnant women and should be offered to lactating individuals similar to non-lactating women who otherwise meet the criteria for vaccination based on the priority groups recommended by ACIP.

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 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.

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). About half of participants were female. The minimum age for the population reported on so far was 16 years and the median age was 52 years, with 21% over 65 years. A subset of adolescents 12-15 years old were added in the latter stages of the study but were not included in this report and should be reported on soon. 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, pregnant/breastfeeding women, and children under 12 years old 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.

Study participants by Race/Ethnicity
Pfizer Moderna
White 83% 79%
Black 9% 10%
Asian 4% 5%
Latinx 28% 20%
Native American 0.5% 0.8%
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). 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.



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 without prior evidence of natural infection. Efficacy remained at least 94% when including participants with prior infection. Efficacy was consistent across demographic subgroups (≥93%). One severe case of COVID-19 occurred in the vaccine group compared to 4 in the placebo group.

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.

There was evidence of over 50% efficacy after one dose of either vaccine in the limited time before the second dose was administered. In a post-hoc analysis of the Moderna data, there was greater than 90% reduction in symptomatic COVID-19 cases in the short interval between 14 days post-dose 1, and before the second dose. There is also evidence of an approximate two-thirds reduction in asymptomatic infection after one dose of the Moderna vaccine in the limited time before the second dose was administered. Further analyses of these data and post-authorization studies are in progress.

Safety Data
Common side effects from Pfizer-BioNTech vaccinations 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.

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 reactions were reported in 1.5% of vaccine recipients compared to 1.1% of placebo recipients; however, no anaphylactic or severe hypersensitivity reactions 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.

Conclusion
Both the Pfizer-BioNTech and Moderna vaccines are two-dose mRNA vaccines that are highly efficacious against COVID-19. Mild to moderate local and systemic side effects are common and should be expected with both vaccines; systemic side effects are more frequent following the second dose, and most local and systemic side effects are less common among older adults. Other than hypersensitivity reactions discussed below, no associations with other adverse events of special interest have been found with either vaccine. Data is currently unavailable among severely immunosuppressed persons, pregnant/breastfeeding women, and children younger than 16 years.

Post-Licensure Safety Surveillance

Post-authorization safety surveillance monitors for and evaluates safety signals that arise after the vaccine is approved for use in the general population.

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 (~5 cases per million doses) and Moderna (~3 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.

Sources

Publications Analyzing Phase III Clinical Trial Data
Pfizer-BioNTech
Moderna

FDA
Emergency Use Authorization Main Page
EUA for Vaccines Explained
Pfizer-BioNTech Briefing
Moderna Briefing
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
Pfizer-BioNTech Fact Sheets and Additional Information
Moderna Fact Sheets and Additional Information

CDC
ACIP COVID-19 Recommendations
Understanding mRNA 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

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
 

The information on this page was last updated on February 20, 2021 | © 2021 Institute for Vaccine Safety