Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: Pfizer-BioNTech COVID-19 Vaccine

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. (Table 1, Table 2)

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

Table 1. Local reactions in persons aged 16-55 years, Pfizer-BioNTech COVID-19 vaccine and Placebo
Dose 1 Dose 2
Pfizer-BioNTech Vaccine
N=2291
Placebo
N=2298
Pfizer-BioNTech Vaccine
N=2098
Placebo
N=2103
Rednessa, n (%)
Any 104 (4.5) 26 (1.1) 123 (5.9) 14 (0.7)
Mild 70 (3.1) 16 (0.7) 73 (3.5) 8 (0.4)
Moderate 28 (1.2) 6 (0.3) 40 (1.9) 6 (0.3)
Severe 6 (0.3) 4 (0.2 10 (0.5) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Swellinga, n (%)
Any 132 (5.8) 11 (0.5) 132 (6.3) 5 (0.2)
Mild 88 (3.8) 3 (0.1) 80 (3.8) 3 (0.1)
Moderate 39 (1.7) 5 (0.2) 45 (2.1) 2 (0.1)
Severe 5 (0.2) 3 (0.1) 7 (0.3) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Pain at the injection siteb, n (%)
Any 1904 (83.1) 322 (14.0) 1632 (77.8) 245 (11.7)
Mild 1170 (51.1) 308 (13.4) 1039 (49.5) 225 (10.7)
Moderate 710 (31.0) 12 (0.5) 568 (27.1) 20 (1.0)
Severe 24 (1.0) 2 (0.1) 25 (1.2) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)

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

Table 2. Local reactions in persons aged >55 years, Pfizer-BioNTech COVID-19 vaccine and Placebo
Dose 1 Dose 2
Pfizer-BioNTech Vaccine
N=1802
Placebo
N=1792
Pfizer-BioNTech Vaccine
N=1660
Placebo
N=1646
Rednessa, n (%)
Any 85 (4.7) 19 (1.1) 120 (7.2) 12 (0.7)
Mild 55 (3.1) 12 (0.7) 59 (3.6) 8 (0.5)
Moderate 27 (1.5) 5 (0.3) 53 (3.2) 3 (0.2)
Severe 3 (0.2) 2 (0.1) 8 (0.5) 1 (0.1)
Grade 4 0 (0.0) 0 (0) 0 (0) 0 (0)
Swellinga, n (%)
Any 118 (6.5) 21 (1.2) 124 (7.5) 11 (0.7)
Mild 71 (3.9) 10 (0.6) 68 (4.1) 5 (0.3)
Moderate 45 (2.5) 11 (0.6) 53 (3.2) 5 (0.3)
Severe 2 (0.1) 0 (0) 3 (0.2) 1 (0.1)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Pain at the injection siteb, n (%)
Any 1282 (71.1) 166 (9.3) 1098 (66.1) 127 (7.7)
Mild 1008 (55.9) 160 (8.9) 792 (47.7) 127 (7.7)
Moderate 270 (15.0) 6 (0.3) 298 (18.0) 2 (0.1)
Severe 4 (0.2) 0 (0) 8 (0.5) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)

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. (Table 3, Table 4)

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

Table 3. Systemic reactions in persons aged 16-55 years, Pfizer-BioNTech COVID-19 vaccine and Placebo
Dose 1 Dose 2
Pfizer-BioNTech Vaccine
N=2291
Placebo
N=2298
Pfizer-BioNTech Vaccine
N=2098
Placebo
N=2103
Fever, n (%)
≥38.0°C 85 (3.7) 20 (0.9) 331 (15.8) 10 (0.5)
≥38.0°C to 38.4°C 64 (2.8) 10 (0.4) 194 (9.2) 5 (0.2)
>38.4°C to 38.9°C 15 (0.7) 5 (0.2) 110 (5.2) 3 (0.1)
>38.9°C to 40.0°C 6 (0.3) 3 (0.1) 26 (1.2) 2 (0.1)
>40.0°C 0 (0) 2 (0.1) 1 (0) 0 (0)
Fatiguea, n (%)
Any 1085 (47.4) 767 (33.4) 1247 (59.4) 479 (22.8)
Mild 597 (26.1) 467 (20.3) 442 (21.1) 248 (11.8)
Moderate 455 (19.9) 289 (12.6) 708 (33.7) 217 (10.3)
Severe 33 (1.4) 11 (0.5) 97 (4.6) 14 (0.7)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Headachea, n (%)
Any 959 (41.9) 775 (33.7) 1085 (51.7) 506 (24.1)
Mild 628 (27.4) 505 (22.0) 538 (25.6) 321 )15.3)
Moderate 308 (13.4) 251 (10.9) 480 (22.9) 170 (8.1)
Severe 23 (1.0) 19 (0.8) 67 (3.2) 15 (0.7)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Chillsa, n (%)
Any 321 (14.0) 146 (6.4) 737 (35.1) 79 (3.8)
Mild 230 (10.0) 111 (4.8) 359 (17.1) 65 (3.1)
Moderate 82 (3.6) 33 (1.4) 333 (15.9) 14 (0.7)
Severe 9 (0.4) 2 (0.1) 45 (2.1) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Vomitingb, n (%)
Any 28 (1.2) 28 (1.2) 40 (1.9) 25 (1.2)
Mild 24 (1.0) 22 (1.0) 28 (1.3) 16 (0.8)
Moderate 4 (0.2) 5 (0.2) 8 (0.4) 9 (0.4)
Severe 0 (0) 1 (0) 4 (0.2) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Diarrheac, n (%)
Any 255 (11.1) 270 (11.7) 219 (10.4) 177 (8.4)
Mild 206 (9.0) 217 (9.4) 179 (8.5) 144 (6.8)
Moderate 46 (2.0) 52 (2.3) 36 (1.7) 32 (1.5)
Severe 3 (0.1) 1 (0) 4 (0.2) 1 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
New or worsening muscle paina, n (%)
Any 487 (21.3) 249 (10.8) 783 (37.3) 173 (8.2)
Mild 256 (11.2) 175 (7.6) 326 (15.5) 111 (5.3)
Moderate 218 (9.5) 72 (3.1) 410 (19.5) 59 (2.8)
Severe 13 (0.6) 2 (0.1) 47 (2.2) 3 (0.1)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
New or worsening joint paina, n (%)
Any 251 (11.0) 138 (6.0) 459 (21.9) 109 (5.2)
Mild 147 (6.4) 95 (4.1) 205 (9.8) 54 (2.6)
Moderate 99 (4.3) 43 (1.9) 234 (11.2) 51 (2.4)
Severe 5 (0.2) 0 (0) 20 (1.0) 4 (0.2)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Use of antipyretic or pain medication 638 (27.8) 332 (14.4) 945 (45.0) 266 (12.6)

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

Table 4. Systemic reactions in persons aged >55 years, Pfizer-BioNTech COVID-19 vaccine and Placebo
Dose 1 Dose 2
Pfizer-BioNTech Vaccine
N=1802
Placebo
N=1792
Pfizer-BioNTech Vaccine
N=1660
Placebo
N=1646
Fever
≥38.0°C 26 (1.4) 7 (0.4) 181 (10.9) 4 (0.2)
≥38.0°C to 38.4°C 23 (1.3) 2 (0.1) 131 (7.9) 2 (0.1)
>38.4°C to 38.9°C 1 (0.1) 3 (0.2) 45 (2.7) 1 (0.1)
>38.9°C to 40.0°C 1 (0.1) 2 (0.1) 5 (0.3) 1 (0.1)
>40.0°C 1 (0.1) 0 (0) 0 (0) 0 (0)
Fatiguea, n (%)
Any 615 (34.1) 405 (22.6) 839 (50.5) 277 (16.8)
Mild 373 (20.7) 252 (14.1) 351 (21.1) 161 (9.8)
Moderate 240 (13.3) 150 (8.4) 442 (26.6) 114 (6.9)
Severe 2 (0.1) 3 (0.2) 46 (2.8) 2 (0.1)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Headachea, n (%)
Any 454 (25.2) 325 (18.1) 647 (39.0) 229 (13.9)
Mild 348 (19.3) 242 (13.5) 422 (25.4) 165 (10.0)
Moderate 104 (5.8) 80 (4.5) 216 (13.0) 60 (3.6)
Severe 2 (0.1) 3 (0.2) 9 (0.5) 4 (0.2)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Chillsa, n (%)
Any 113 (6.3) 57 (3.2) 377 (22.7) 46 (2.8)
Mild 87 (4.8) 40 (2.2) 199 (12.0) 35 (2.1)
Moderate 26 (1.4) 16 (0.9) 161 (9.7) 11 (0.7)
Severe  0 (0) 1 (0.1) 17 (1.0) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Vomitingb, n (%)
Any 9 (0.5) 9 (0.5) 11 (0.7) 5 (0.3)
Mild 8 (0.4) 9 (0.5) 9 (0.5) 5 (0.3)
Moderate 1 (0.1) 0 (0) 1 (0.1) 0 (0)
Severe 3 (0.2) 0 (0) 1 (0.1) 0 (0)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Diarrheac, n (%)
Any 147 (8.2) 118 (6.6) 137 (8.3) 99 (6.0)
Mild 118 (6.5) 100 (5.6) 114 (6.9) 73 (4.4)
Moderate 26 (1.4) 17 (0.9) 21 (1.3) 22 (1.3)
Severe 3 (0.2) 1 (0.1) 2 (0.1) 4 (0.2)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
New or worsening muscle paina, n (%)
Any 251 (13.9) 149 (8.3) 477 (28.7) 87 (5.3)
Mild 168 (9.3) 100 (5.6) 202 (12.2) 57 (3.5)
Moderate 82 (4.6) 46 (2.6) 259 (15.6) 29 (1.8)
Severe 1 (0.1) 3 (0.2) 16 (1.0) 1 (0.1)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
New or worsening joint paina, n (%)
Any 155 (8.6) 109 (6.1) 313 (18.9) 61 (3.7)
Mild 101 (5.6) 68 (3.8) 161 (9.7) 35 (2.1)
Moderate 52 (2.9) 40 (2.2) 145 (8.7) 25 (1.5)
Severe 2 (0.1) 1 (0.1) 7 (0.4) 1 (0.1)
Grade 4 0 (0) 0 (0) 0 (0) 0 (0)
Use of antipyretic or pain medication 358 (19.9) 213 (11.9) 625 (37.7) 161 (9.8)

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 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

Page last reviewed: December 13, 2020