Pfizer-BioNTech COVID-19 Vaccine Reactions & Adverse Events

Persons Aged 6 Months – 4 Years

Local Reactions

Local reactions were reported by half (48%) of vaccine recipients and at higher rates than placebo recipients. Vaccine recipients reported similar rates of local reactions after dose 1 and dose 2, but slightly lower after dose 3. Pain/tenderness at the injection site was the most frequent and severe reported solicited local reaction among vaccine recipients. After dose 1, the older age group (2 – 4 years) reported pain/tenderness more frequently than the younger age group (6 – 23 months) (30.8% vs 16.6%); a similar pattern was observed after dose 2 and 3 (31.0% vs 15.0% and 26.7% vs 16.0%, respectively). Injection site redness was the second most frequently reported local reaction. Redness was reported slightly more frequently in the older age group than the younger age group (10.9% vs 7.5% after dose 3). Injection site swelling following either dose was reported less frequently. Redness and swelling were more common after dose 2 than dose 1 or 3. No grade 4 local reactions were reported. Overall, the median onset of local reactions in the vaccine group was 1 to 2 days after either dose, with a median duration of 1 day after onset.

Table 1. Local reactions in persons aged 6-23 months, Pfizer BioNTech BNT162b2 COVID-19 vaccine and placebo

^aMild: ≥0.5 to 2.0 cm; moderate: >2.0 to 7.0 cm; severe: >7.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only)

^bMild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: causes limitation of limb movement; Grade 4: emergency room visit or hospitalization for severe tenderness at the injection site.

Table 2. Local reactions in persons aged 2 – 4 years, Pfizer BioNTech BNT162b2 COVID-19 vaccine and placebo

^a Mild: ≥0.5 to 2.0 cm; moderate: >2.0 to 7.0 cm; severe: >7.0 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

Systemic Reactions

Solicited systemic adverse reactions were most common in the vaccine group than the placebo group. The most common solicited systemic adverse reaction after any dose was irritability (43.6% – 51.2%) among ages 6 – 23 months and fatigue (24.5% – 29.7%) among ages 2 – 4 years. The majority of systemic events were mild or moderate in severity, but there was a higher occurrence of grade 3 or higher reactions in the vaccine group. Fever >40°C was reported in the 6 – 23 month age group (placebo: 1/597, 0.2%; vaccine: 3/1177, 0.3%) and the 2 – 4 year age group (placebo: 0/909, 0.0%; vaccine: 3/1824, 0.2%;). The median onset for most systemic events in the 6 – 23 month age group was 2 days after any dose and all events resolved with a duration of 1 to 2 days after onset. The median onset for most systemic events in the 2 – 4 year age group was 2 days after any dose and all events resolved with a duration of 1 – 2 days after onset.

Table 3. Systemic reactions in persons aged 6–23 months, Pfizer BioNTech BNT162b2 COVID-19 vaccine and placebo

^a Any fever= ≥38.0°C
^b Mild: decreased interest in eating; moderate: decreased oral intake; severe: refusal to feed; Grade 4: emergency room visit or hospitalization
^c Mild: increased or prolonged sleeping bouts; moderate: slightly subdued interfering with daily activity; severe: disabling; not interested in usual daily activity; Grade 4: emergency room visit or hospitalization
^d Mild: easily consolable; moderate: requiring increased attention; severe: inconsolable; crying cannot be comforted; Grade 4: emergency room visit or hospitalization

Table 4. Systemic reactions in children 2-4 years, Pfizer BioNTech BNT162b2 COVID-19 vaccine and placebo

^a Any fever= ≥38.0°C
^b Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization
^c 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
^d 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

Unsolicited Adverse Events

The overall incidence of unsolicited non-serious adverse events from dose 1 to data cutoff (April 29, 2022) were similar in the vaccine and placebo groups in both age groups: 29.1% vs. 26.3% for the younger age group and 18.5% vs. 18.5% in the older age group, respectively. The most commonly observed adverse events were consistent with those reported as local and systemic reactions and/or were consistent with events frequently reported in this age group, including infections and injuries, that were not considered related to vaccination. Lymphadenopathy was reported by 2 (0.2%) vaccine recipients 6-23 months of age, 1 (0.1%) vaccine recipient 2 – 4 years of age, and no placebo recipients.

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 or incapacity.

Few SAEs were reported from dose 1 to data cutoff (April 29, 2022) among the vaccine and placebo groups, (1.4% and 2.3%, respectively in the younger age group and 0.7% and 0.9%, respectively in the older age group). Most SAEs were gastrointestinal or respiratory infections/illnesses that occur commonly in this age group. One vaccine recipient reported two SAEs (fever and pain in extremity requiring hospitalization) which were considered potentially related by the investigator and FDA. FDA noted that the events were also consistent with viral myositis. The remaining SAEs were considered by FDA to be unrelated to the study vaccine.

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 5)

Table 5. 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 6)

Table 6. 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 | FDA

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 7 below.

Table 7. 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 8 below.

Table 8. 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 Memo

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 9 and Table 10 immediately below this paragraph.

Table 9. 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 10. 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 11 and Table 12 immediately below this paragraph.

Table 11. 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 12. 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 document