This page summarizes findings from the Phase 3 study testing the efficacy and safety of the Moderna COVID-19 vaccine, mRNA-1273. About 30,000 people enrolled in this study. Half of them received the mRNA-1273 vaccine, while the other half received a placebo vaccine. A brief summary of the design of this study can be found in Table 1 on this website. More detailed information about the design of the study can be found on ClinicalTrials.Gov and the full protocol for the study can be found here.
Most of the data summarized on this page are from analyses that Moderna and the US Food and Drug Administration (FDA) conducted from mid-November to early December 2020. At the time of these analyses, study participants had been followed an average of 9 weeks after receiving the first vaccine dose. However, some participants had been followed for as long as 15 weeks. The study is continuing and the findings may change somewhat as more data are collected.
At the bottom of this page, we provide links to more detailed information prepared by Moderna, the FDA, and the Centers for Disease Control and Prevention (CDC).
The figure below shows when the cases of COVID-19 occurred in the groups that received a placebo vaccine (lighter gray line) and the mRNA-1273 vaccine (darker line). This figure is from the slides that Moderna presented at the FDA advisory committee meeting on December 17, 2020. The figure suggests that the mRNA-1273 vaccine starts to provide protection around 2 to 3 weeks following the first dose and continues to provide protection for at least 90 days. As participants in the study are followed longer, this type of figure will give us an idea of the extent to which vaccine efficacy may decrease over time. (You can click on the figure to enlarge it.)
For seven days after receiving an injection (either the mRNA-1273 vaccine or the placebo vaccine), study participants completed an electronic diary each day. The diary included a list of possible vaccine side effects. Participants were asked to check any side effects they were having that day and to provide information about the severity of the side effect. The list included both local (e.g., pain at the injection site) and systemic side effects (e.g., fever). Information reported in these diaries is presented in the figures below.
Local Side Effects: Any Severity
The figure below shows the percentage of participants who had local side effects of any severity. On average, these side effects started on the day of the injection and lasted for 2 days following the first dose and 3 days following the second dose. Participants age 65 and older were somewhat less likely to report local side effects than younger participants.
Local Side Effects: Grade 3 Severity Only
The figure below shows the percentage of participants who had local side effects that were rated as Grade 3 in severity. Pain at the injection site and lymph nodes swelling/tenderness were rated as Grade 3 if the participant reported that they used a prescription pain medication to control the side effect or that the side effect prevented them from doing their normal daily activities. Injection side redness and swelling was rated as Grade 3 in severity if it involved an area larger than 10 cm (about 4 inches). This figure indicates that few study participants had Grade 3 local side effects. In addition, no participants reported a Grade 4 (the most severe) local side effect.
Systemic Side Effects: Any Severity
The figure below shows the percentage of participants who had systemic side effects of any severity. Most of these side effects (70.7%) started either the same day a participant received the vaccine or the next day. The side effects lasted an average of 2 days after each dose. Most of the systemic side effects were reported less often by participants age 65 and older than younger participants.
Systemic Side Effects: Grade 3 or 4 Severity Only
The figure below shows the percentage of participants who had systemic side effects that were rated Grade 3 or Grade 4 in severity. Fevers between 102.1° F and 104.0° F were rated Grade 3. Other systemic side effects were rated Grade 3 if they prevented daily activities days. Fevers over 104.0° F were rated Grade 4. Other systemic side effects were rated Grade 4 if they required an emergency room visit or hospitalization. A total of 26 Grade 4 side effects were reported (17 in the mRNA-1273 group and 9 in the placebo group). Most of these involved fevers of greater than 104.0° F (4 in the mRNA-1273 group after Dose 1, 11 in the mRNA-1273 group after Dose 2, 6 in the placebo group after Dose 1, and 3 in the placebo group after Dose 2). Participants age 65 and older were less likely than younger participants to report Grade 3/4 systemic side effects.
Other Potential Side Effects
In addition to completing daily diaries for 7 days after receiving each vaccine dose, participants in the study are being called once a month for the next two years to determine if the mRNA-1273 vaccine has any unexpected serious side effects. During these calls, participants are asked if they have experienced any health problems during the past month. The health problems reported are analyzed to determine if there are differences between those who received the mRNA-1273 vaccine and those who received the placebo vaccine.
As of November 25, 2020, only a few differences have been found between the two groups. Among the ~30,000 study participants (followed for an average of 9 weeks at this point):
- 4 people (3 in the mRNA group and 1 in the placebo group) experienced Bell’s Palsy. All of these cases appeared 2-4 weeks after vaccination. Bell’s Palsy is a condition that can cause temporary weakness or paralysis of facial muscles. As a result, one side of the face may droop or become stiff. The FDA considered 1 of these 4 cases of Bell’s Palsy a serious adverse event. It occurred in a 67 year-old woman with diabetes who had received the mRNA-1273 vaccine. The FDA concluded that not enough information is available to determine if the mRNA-1273 can cause Bell’s Palsy. It is possible that the small difference between the mRNA-1273 group and the placebo group occurred by chance.
- 2 people (both in the mRNA group) developed facial swelling. Both of these individuals had a history of injection with dermatological fillers. The swelling started 1 to 2 days after vaccination. The FDA considered these serious adverse events likely related to vaccination.
- 1 person in the mRNA-1273 group developed intractable nausea and vomiting that started 1 day after vaccination. This participant had a history of severe headache and nausea requiring hospitalization. The FDA considered this a serious adverse event likely related to vaccination.
Questions That Remain
Unknown Benefits/Data Gaps
- Duration of protection. Currently, only about 5,000 study participants have been followed more than 90 days after receiving their first dose of the mRNA-1273 vaccine. Therefore, at this point in time, it is not possible to determine how long protection from COVID-19 is likely to last.
- Vaccine effectiveness against asymptomatic infection. Moderna presented some data suggesting that the mRNA-1273 vaccine may help protect against asymptomatic infection. All participants were tested for infection with SARS-CoV-2 before they received the first vaccine dose and again four weeks later (before they received the second dose). Among the people who were negative for SARS-CoV-2 infection before the first dose, 38 people (0.3%) who received the placebo vaccine tested positive for SARS-CoV-2 four weeks later, compared to 14 of the people (0.1%) who received the mRNA-1273 vaccine. This suggests that the mRNA-1273 vaccine may help prevent asymptomatic infection, but more data are needed to draw firm conclusions. In addition, more data are needed to determine if the mRNA-1273 vaccine helps prevent virus shedding and transmission, particularly among people with asymptomatic infections.
- Vaccine effectiveness against mortality and long-term health effects of COVID-19. It is reasonable to expect that the mRNA-1273 vaccine will reduce the risk of dying from COVID-19 or experiencing long-term health problems (e.g., organ damage) as a result of the disease. However, more data are needed to confirm these potential benefits. It is likely that answers to these questions will come from observational studies involving millions of people. People in observational studies are not randomized to receive a particular type of treatment. Therefore, no one would be required to get the mRNA-1273 vaccine and no one would be denied the vaccine. Nonetheless, researchers can use data from observational studies to see if there are differences in health outcomes (e.g., death, hospitalization) between people who received a certain type of treatment (for example, the mRNA-1273 vaccine) and those who did not.
Unknown Risks/Data Gaps
- Pregnancy and Lactation: The Phase 3 trial excluded women who were pregnant or breastfeeding at the start of the trial and female participants of child-bearing potential agreed to practice adequate conception for 3 months following the second vaccine dose. Most clinical trials of investigational drugs do not include pregnant women, so this is not unusual. If you would like more information about the inclusion of pregnant women in clinical trials, see this FDA Guidance document.
In spite of the exclusion of pregnant women from the Phase 3 trial, 6 women in the mRNA-1273 group became pregnant shortly after receiving the vaccine. As of December 2, 2020, these 6 women have not reported any adverse pregnancy outcomes.
The FDA advises women who are pregnant or breastfeeding to discuss their options for vaccination with their healthcare provider.
Why might a woman who is pregnant consider getting the mRNA-1273 vaccine? First, among women with COVID-19, research suggests that pregnancy may increase the risk of severe disease. (See these two reports from CDC for more information 1, 2.) Second, among pregnant women, getting COVID-19 may increase the risk of preterm birth. Being vaccinated against COVID-19 may lower these risks. Finally, certain medical conditions increase the risk of developing severe COVID-19. Therefore, it is especially important for women with any of these conditions to discuss their options for vaccination with their healthcare provider.
The information in the box below is taken directly from the FDA-approved Fact Sheet for Healthcare Providers (pages 17-18), dated 12/2020.
Pregnancy Exposure Registry. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Moderna COVID-19 Vaccine during pregnancy. Women who are vaccinated with Moderna COVID-19 Vaccine during pregnancy are encouraged to enroll in the registry by calling 1-866-MODERNA (1-866-663-3762).
Risk Summary All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on Moderna COVID-19 Vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.
In a developmental toxicity study, 0.2mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (100 mcg) and other ingredients included in a single human dose of Moderna COVID-19 Vaccine was administered to female rats by the intramuscular route on four occasions: 28 and 14 days prior to mating, and on gestation days 1 and 13. No vaccine-related adverse effects on female fertility, fetal development or postnatal development were reported in the study.
Data are not available to assess the effects of Moderna COVID-19 Vaccine on the breastfed infant or on milk production/excretion.
- Adverse reactions that are very uncommon or that require longer follow-up to detect. In the Phase 3 trial, about 15,000 people received the mRNA-1273 vaccine. This may not be enough to discover uncommon (and potentially serious) side effects. In addition, when the FDA issued the emergency use authorization (EUA) for the mRNA-1273 vaccine in December 2020, study participants had only been followed for an average of 9 weeks. The FDA considered this an adequate length of follow-up for the purpose of issuing the EUA because historical data indicate that most adverse events from vaccines occur within 6 weeks following vaccination. Nonetheless, surveillance systems (including, the Vaccine Adverse Event Reporting System, VAERS, and v-safe) are in place to detect uncommon or delayed adverse events as soon as possible under the EUA.
- Vaccine-enhanced disease. Data from the Phase 3 trial suggest that the mRNA-1273 vaccine helps protect against severe COVID-19. However, it is still unknown if the risk of more severe disease following vaccination may increase over time, especially if immunity decreases over time. Study participants continue to be followed to assess this potential risk.
- Severe allergic reactions. No one in the Phase 3 trial had an anaphylactic or severe allergic reaction immediately after receiving the mRNA-1273 vaccine. However, since the vaccine has become available under the EUA at least one severe allergic reaction has been reported. The FDA recommends that people not get the mRNA-1273 vaccine if they have had a severe allergic reaction after a previous dose of the mRNA-1273 vaccine or if they have had a severe allergic reaction to any of the ingredients in the vaccine. The list of ingredients in the vaccine is available in the Fact Sheet for Healthcare Providers. More information about COVID-19 vaccines and how healthcare providers can manage severe allergic reactions if they occur is available from the CDC.
- Individuals who are immunocompromised. The FDA concluded that there is not enough information to draw conclusions about the safety and efficacy of the mRNA-1273 vaccine in individuals who are immunocompromised. Individuals who are immunocompromised or on a medication that affects the immune system are advised to talk to their health care provider. More information about vaccination decisions for people with underlying medical conditions is available from the CDC.
- 84-page briefing document and 7-page addendum to the briefing document prepared by Moderna when requesting an emergency use authorization for mRNA-1273.
- 54-page briefing document prepared by the FDA after reviewing the materials submitted by Moderna.
- 22-page Fact Sheet for Healthcare Providers Administering Vaccine
- 5-page Fact Sheet for Recipients and Caregivers