Persons Aged ≥18 Years

Local Reactions

Among all study vaccine recipients asked to complete diaries of their symptoms during the 7 days after vaccination, 84.7% reported at least one local injection site reaction. By age group, 88.7% in the younger group (aged 18 to 55 years) and 79.7% in the older group (aged >55 years) reported at least one local reaction. Pain at the injection site was the most frequent and severe solicited local reaction among vaccine recipients. After dose 1, the younger age group reported pain more frequently than the older age group (83.1% vs 71.1%); a similar pattern was observed after dose 2 (77.8% vs 66.1%). Injection site redness and swelling following either dose were reported less frequently than injection site pain. Redness and swelling were slightly more common after dose 2. No grade 4 local reactions were reported. Overall, the median onset of local reactions in the vaccine group was 0 (day of vaccination) to 2 days after either dose and lasted a median duration between 1 and 2 days. Data on local reactions were not solicited from persons aged 16-17 years. However, their reactions to vaccination are expected to be similar to those of young adults who were included. In addition, reactogenicity data from adolescents aged 12-15 years were obtained and reviewed, and were similar to those from adults aged 18-55 years. This data is presented in Table 1 and Table 2 immediately below this paragraph.

Table 1. Local reactions in persons aged 18-55 years, Pfizer-BioNTech COVID-19 vaccine and placebo

aMild: >2.0 to 5.0 cm; moderate: >5.0 to 10.0 cm; severe: >10.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only).

bMild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe pain at the injection site.

Table 2. Local reactions in persons aged >55 years, Pfizer-BioNTech COVID-19 vaccine and placebo

a Mild: >2.0 to 5.0 cm; moderate: >5.0 to 10.0 cm; severe: >10.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only).

b Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe pain at the injection site.

Systemic Reactions

Among all vaccine recipients asked to complete diaries of their symptoms during the 7 days after vaccination, 77.4% reported at least one systemic reaction. The frequency of systemic adverse events was higher in the younger than the older age group (82.8% vs 70.6%). Within each age group, the frequency and severity of systemic adverse events was higher after dose 2 than dose 1. Vomiting and diarrhea were exceptions, and similar between vaccine and placebo groups and regardless of dose. For both age groups, fatigue, headache and new or worsened muscle pain were most common. The majority of systemic events were mild or moderate in severity, after both doses and in both age groups. Fever was more common after the second dose and in the younger group (15.8%) compared to the older group (10.9%). Overall, the median onset of systemic adverse events in the vaccine group in general was 1 to 2 days after either dose and lasted a median duration of 1 day. Four grade 4 fevers (>40.0°C) were reported, two in the vaccine group and two in the placebo group. No other systemic grade 4 reactions were reported. Data on systemic reactions were not solicited from persons aged 16-17 years. However, their reactions to vaccination are expected to be similar to those of young adults who were included. In addition, reactogenicity data from adolescents aged 12-15 years were obtained and reviewed, and were similar to those from adults aged 18-55 years. This data is presented in Table 3 and Table 4 immediately below this paragraph.

Table 3. Systemic reactions in persons aged 18-55 years, Pfizer-BioNTech COVID-19 vaccine and placebo

a Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe fatigue, severe headache, severe muscle pain, or severe joint pain.

b Mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or hospitalization for severe vomiting.

cMild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours; Grade 4: emergency room visit or hospitalization for severe diarrhea.

Table 4. Systemic reactions in persons aged >55 years, Pfizer-BioNTech COVID-19 vaccine and placebo

Unsolicited Adverse Events

Reports of lymphadenopathy were imbalanced with 58 more cases in the vaccine group (64) than the placebo group (6); lymphadenopathy is plausibly related to the vaccine. Lymphadenopathy occurred in the arm and neck region and was reported within 2 to 4 days after vaccination. The average duration of lymphadenopathy was approximately 10 days. Bell’s palsy was reported by four vaccine recipients and none of the placebo recipients. The observed frequency of reported Bell’s palsy in the vaccine group is consistent with the background rate in the general population, and there is no basis upon which to conclude a causal relationship.

Serious Adverse Events

Serious adverse events were defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, or resulted in persistent disability/incapacity. The proportions of participants who reported at least 1 serious adverse event were 0.6% in the vaccine group and 0.5% in the placebo group. The most common serious adverse events in the vaccine group which were numerically higher than in the placebo group were appendicitis (7 in vaccine vs 2 in placebo), acute myocardial infarction (3 vs 0), and cerebrovascular accident (3 vs 1). Cardiovascular serious adverse events were balanced between vaccine and placebo groups. Two serious adverse events were considered by U.S. Food and Drug Administration (FDA) as possibly related to vaccine: shoulder injury possibly related to vaccine administration or to the vaccine itself, and lymphadenopathy involving the axilla contralateral to the vaccine injection site. Otherwise, occurrence of severe adverse events involving system organ classes and specific preferred terms were balanced between vaccine and placebo groups.

Data source: FDA briefing documentexternal icon

Persons Aged 12 – 15 Years

Local Reactions

Among all study vaccine recipients aged 12–15 years, 90.9% reported at least one local injection site reaction in the 7 days after vaccination. Pain at the injection site was the most frequent and severe solicited local reaction among vaccine recipients and was slightly more common after dose 2. No grade 4 local reactions were reported. The median onset of local reactions in the vaccine group was 0 (day of vaccination) to 2 days after either dose and lasted a median duration between 1 and 3 days. This data is presented in Table 5 below.

Table 5. Local reactions in persons aged 12-15 years, Pfizer-BioNTech COVID-19 vaccine and placebo

aMild: >2.0 to 5.0 cm; moderate: >5.0 to 10.0 cm; severe: >10.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only).

bMild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe pain at the injection site.

Systemic Reactions

Among all vaccine recipients, 90.7% reported at least one systemic reaction in the 7 days after vaccination. The frequency and severity of systemic adverse events was higher after dose 2 than dose 1. Vomiting and diarrhea were exceptions, and similar between vaccine and placebo groups and regardless of dose. Fatigue, headache, chills, and new or worsened muscle pain were most common. The majority of systemic events were mild or moderate in severity, after both doses. Fever was more common after the second dose than after the first dose. Overall, the median onset of systemic adverse events in the vaccine group in general was 1 to 3 days after either dose and lasted a median duration of 1 to 2 days. One grade 4 fever (>40.0°C) was reported in the vaccine group. No other systemic grade 4 reactions were reported. This data is presented in Table 6 below.

Table 6. Systemic reactions in persons aged 12-15 years, Pfizer-BioNTech COVID-19 vaccine and placebo

a Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe fatigue, severe headache, severe muscle pain, or severe joint pain.

b Mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or hospitalization for severe vomiting.

c Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours; Grade 4: emergency room visit or hospitalization for severe diarrhea.

Unsolicited Adverse Events

Reports of lymphadenopathy were imbalanced with 6 more cases in the vaccine group (7) than the placebo group (1); lymphadenopathy is plausibly related to the vaccine. Lymphadenopathy occurred in the arm and neck region and was reported within 2 to 4 days after vaccination. Most cases of lymphadenopathy resolved in 10 days or less. No bell’s palsy or anaphylaxis was reported among vaccine recipients in this age group.

Serious Adverse Events

The proportions of participants who reported at least 1 serious adverse event were 0.4% in the vaccine group and 0.2% in the placebo group. No serious adverse events were considered by FDA as possibly related to vaccine.

Data source: FDA Decision Memoexternal icon

Persons Aged 5 – 11 Years

Local Reactions

Among all study vaccine recipients aged 5–11 years, 86.2% reported at least one local injection site reaction in the 7 days after vaccination. Pain at the injection site was the most frequent and severe solicited local reaction among vaccine recipients and was slightly more common after dose 1. No grade 4 local reactions were reported. The median onset of local reactions in the vaccine group was 1 to 2 days after either dose and lasted a median duration between 1 and 2 days. (Table 7)

Table 7. Local reactions in persons aged 5–11 years, Pfizer-BioNTech COVID-19 vaccine and placebo

aMild: >2.0 to 5.0 cm; moderate: >5.0 to 10.0 cm; severe: >10.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only).

bMild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe pain at the injection site.

Systemic Reactions

Among all vaccine recipients, 66.6% reported at least one systemic reaction in the 7 days after vaccination. The frequency and severity of systemic adverse events was higher after dose 2 than dose 1. Fatigue, headache, chills, and new or worsened muscle pain were most common. The majority of systemic events were mild or moderate in severity, after both doses. Fever was more common after the second dose than after the first dose. Overall, the median onset of systemic adverse events in the vaccine group in general was 1 to 4 days after either dose and lasted a median duration of 1 day. One grade 4 fever (>40.0°C) was reported in the vaccine group. No other systemic grade 4 reactions were reported. (Table 8)

Table 8. Systemic reactions in persons aged 5–11 years, Pfizer-BioNTech COVID-19 vaccine and placebo

a Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe fatigue, severe headache, severe muscle pain, or severe joint pain.

b Mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or hospitalization for severe vomiting.

c Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours; Grade 4: emergency room visit or hospitalization for severe diarrhea.

Unsolicited Adverse Events

Reports of lymphadenopathy were imbalanced. Thirteen participants (0.9%) in the vaccine group and 1 participant (0.1%) in the placebo group had events of lymphadenopathy. The median time to onset was 2-3 days after either dose and all cases resolved within 2 weeks.

Among a safety expansion cohort (over 2250 children randomized 2:1 vaccine to placebo), 6 participants (0.4%) in the vaccine arm and 3 participants (0.4%) in the placebo arm had events of lymphadenopathy. No Bell’s palsy, anaphylaxis or myocarditis was reported among vaccine recipients in this age group.

Serious Adverse Events

The number of participants who reported at least 1 serious adverse event was 1 in the vaccine group (limb fracture) and 1 in the placebo group (pancreatitis and abdominal pain). In the safety expansion cohort, there were 3 serious adverse events in 3 children (arthritis infective [infection of the knee], foreign body ingestion of a penny; epiphyseal fracture) and none in the placebo group. No serious adverse events were considered as possibly related to the vaccine.

Data source: Comirnaty and Pfizer-BioNTech COVID-19 Vaccine | FDAexternal icon