Vaccine Information: Pfizer-BioNTech Covid-19 Vaccine, Bivalent (Page 4 of 14)
5.3 Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.
5.4 Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressive therapy, may have a diminished response to Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
5.5 Limitations of Vaccine Effectiveness
Pfizer-BioNTech COVID-19 Vaccine, Bivalent may not protect all vaccine recipients.
6 ADVERSE REACTIONS
The safety data accrued with the Pfizer-BioNTech COVID-19 Vaccine (no longer authorized for use in the U.S.) and Pfizer-BioNTech’s bivalent COVID-19 vaccine (Original and Omicron BA.1) [not authorized or approved in the U.S., hereafter referred to as bivalent vaccine (Original and Omicron BA.1)] are relevant to Pfizer-BioNTech COVID-19 Vaccine, Bivalent because these vaccines are manufactured using the same process.
The safety of Pfizer-BioNTech COVID-19 Vaccine, Bivalent in individuals 6 months of age and older is based on:
- •
- safety data from clinical studies which evaluated primary and booster vaccination with Pfizer-BioNTech COVID-19 Vaccine,
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- safety data from clinical studies which evaluated booster vaccination with Pfizer-BioNTech COVID-19 Vaccine, Bivalent,
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- safety data from a clinical study which evaluated a booster dose of bivalent vaccine (Original and Omicron BA.1), and
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- postmarketing safety data with Pfizer-BioNTech COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
Pfizer-BioNTech COVID-19 Vaccine
The safety of the primary series Pfizer-BioNTech COVID-19 Vaccine was evaluated in participants 6 months of age and older in 3 clinical studies conducted in the United States, Europe, Turkey, South Africa and South America.
Study BNT162-01 (Study 1) was a Phase 1/2, 2-part, dose-escalation trial that enrolled 60 participants, 18 through 55 years of age. Study C4591001 (Study 2) is a Phase 1/2/3, multicenter, multinational, randomized, saline placebo-controlled, observer-blind, dose finding, vaccine candidate-selection (Phase 1) and efficacy (Phase 2/3) study that has enrolled approximately 46,000 participants, 12 years of age and older. Of these, approximately 43,448 participants [21,720 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA); 21,728 placebo] in Phase 2/3 are 16 years of age or older (including 138 and 145 participants 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 participants are 12 through 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively). Study C4591007 (Study 3) is a Phase 1/2/3 multicenter, randomized, dose finding, open label (Phase 1) and multinational, saline placebo-controlled, observer-blind, immunogenicity and efficacy (Phase 2/3) study that has enrolled 4,695 participants 5 through 11 years of age, of whom 3,109 participants received Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 1,538 participants received placebo in Phase 2/3. Study 3 also enrolled 1,776 participants 6 through 23 months of age, of whom 1,178 participants were in the Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) group and 598 participants in the placebo group; and also enrolled 2,750 participants 2 through 4 years of age, of whom 1,835 participants were in the Pfizer-BioNTech COVID-19 Vaccine group and 915 participants in the placebo group in Phase 2/3.
In Study 2 and Study 3, all participants 6 months through 4 years of age, 5 through 11 years of age, 12 through 15 years of age, and a subset of participants 16 years of age and older, were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination in an electronic diary. Participants are being monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month after the last vaccination (all unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination].
Pfizer-BioNTech COVID-19 Vaccine Administered as a Primary Series
Participants 16 Years of Age and Older (2-Dose Primary Series)
At the time of the analysis of Study 2 for the EUA, 37,586 [18,801 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) and 18,785 placebo] participants 16 years of age or older had been followed for a median of 2 months after the second dose.
The safety evaluation in Study 2 is ongoing. The safety population includes participants 16 years of age and older enrolled by October 9, 2020, and includes safety data accrued through November 14, 2020.
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Overall, among the total participants who received either the Pfizer-BioNTech COVID-19 Vaccine or placebo, 50.6% were male and 49.4% were female, 83.1% were White, 9.1% were Black or African American, 28.0% were Hispanic/Latino, 4.3% were Asian, and 0.5% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
Across both age groups, 18 through 55 years of age and 56 years of age and older, the mean duration of pain at the injection site after Dose 2 was 2.5 days (range 1 to 36 days), for redness 2.6 days (range 1 to 34 days), and for swelling 2.3 days (range 1 to 34 days) for participants in the Pfizer-BioNTech COVID-19 Vaccine group.
Solicited reactogenicity data in 16 and 17 year-old participants are limited.
| Pfizer-BioNTech COVID-19 Vaccine ‡ Dose 1 N § =2291 n ¶ (%) | Placebo Dose 1 N § =2298 n ¶ (%) | Pfizer-BioNTech COVID-19 Vaccine ‡ Dose 2 N § =2098 n ¶ (%) | Placebo Dose 2 N § =2103 n ¶ (%) | |
|---|---|---|---|---|
| Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | ||||
| ||||
| Redness # | ||||
| Any (>2 cm) | 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 (0.0) |
| Swelling # | ||||
| Any (>2 cm) | 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 (0.0) |
| Pain at the injection site Þ | ||||
| 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 (0.0) |
| Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. | ||||
| ||||
| Fever | ||||
| ≥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 (0.0) | 2 (0.1) | 1 (0.0) | 0 (0.0) |
| Fatigue # | ||||
| 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) |
| Headache # | ||||
| 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) |
| Chills # | ||||
| 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 (0.0) |
| Vomiting Þ | ||||
| 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 (0.0) | 1 (0.0) | 4 (0.2) | 0 (0.0) |
| Diarrhea ß | ||||
| 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 (0.0) | 4 (0.2) | 1 (0.0) |
| New or worsened muscle pain # | ||||
| 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) |
| New or worsened joint pain # | ||||
| 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 (0.0) | 20 (1.0) | 4 (0.2) |
| Use of antipyretic or pain medication à | 638 (27.8) | 332 (14.4) | 945 (45.0) | 266 (12.6) |
| Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | ||||
| ||||
| Redness ¶ | ||||
| Any (>2 cm) | 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) |
| Swelling ¶ | ||||
| Any (>2 cm) | 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 (0.0) | 3 (0.2) | 1 (0.1) |
| Pain at the injection site # | ||||
| Any (>2 cm) | 1282 (71.1) | 166 (9.3) | 1098 (66.1) | 127 (7.7) |
| Mild | 1008 (55.9) | 160 (8.9) | 792 (47.7) | 125 (7.6) |
| Moderate | 270 (15.0) | 6 (0.3) | 298 (18.0) | 2 (0.1) |
| Severe | 4 (0.2) | 0 (0.0) | 8 (0.5) | 0 (0.0) |
| Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. | ||||
| ||||
| 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) | 0 (0.0) |
| Fatigue ¶ | ||||
| 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) |
| Headache ¶ | ||||
| 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) |
| Chills ¶ | ||||
| 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 (0.0) | 1 (0.1) | 17 (1.0) | 0 (0.0) |
| Vomiting # | ||||
| 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 (0.0) | 1 (0.1) | 0 (0.0) |
| Severe | 0 (0.0) | 0 (0.0) | 1 (0.1) | 0 (0.0) |
| Diarrhea Þ | ||||
| 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) |
| New or worsened muscle pain ¶ | ||||
| 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) |
| New or worsened joint pain ¶ | ||||
| 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) |
| Use of antipyretic or pain medication | 358 (19.9) | 213 (11.9) | 625 (37.7) | 161 (9.8) |
Unsolicited Adverse Events
Serious Adverse Events
In Study 2, among participants 16 through 55 years of age who had received at least 1 dose of vaccine or placebo (Pfizer-BioNTech COVID-19 Vaccine = 10,841; placebo = 10,851), serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.3% of placebo recipients. In a similar analysis, in participants 56 years of age and older (Pfizer-BioNTech COVID-19 Vaccine = 7,960, placebo = 7,934), serious adverse events were reported by 0.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.6% of placebo recipients who received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine or placebo, respectively. In these analyses, 91.6% of study participants had at least 30 days of follow-up after Dose 2.
Appendicitis was reported as a serious adverse event for 12 participants, and numerically higher in the vaccine group, 8 vaccine participants and 4 placebo participants. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.
Non-Serious Adverse Events
In Study 2 in which 10,841 participants 16 through 55 years of age received Pfizer-BioNTech COVID-19 Vaccine and 10,851 participants received placebo, non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported in 29.3% of participants who received Pfizer-BioNTech COVID-19 Vaccine and 13.2% of participants in the placebo group, for participants who received at least 1 dose. Overall, in a similar analysis in which 7,960 participants 56 years of age and older received Pfizer-BioNTech COVID-19 Vaccine, non-serious adverse events within 30 days were reported in 23.8% of participants who received Pfizer-BioNTech COVID-19 Vaccine and 11.7% of participants in the placebo group, for participants who received at least 1 dose. In these analyses, 91.6% of study participants had at least 30 days of follow-up after Dose 2.
The higher frequency of reported unsolicited non-serious adverse events among Pfizer-BioNTech COVID-19 Vaccine recipients compared to placebo recipients was primarily attributed to local and systemic adverse events reported during the first 7 days following vaccination that are consistent with adverse reactions solicited among participants in the reactogenicity subset and presented in Tables 3 and 4. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy were imbalanced with notably more cases in the Pfizer-BioNTech COVID-19 Vaccine group (64) vs. the placebo group (6), which is plausibly related to vaccination. Throughout the safety follow-up period to date, Bell’s palsy (facial paralysis) was reported by 4 participants in the Pfizer-BioNTech COVID-19 Vaccine group. Onset of facial paralysis was Day 37 after Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of Bell’s palsy were reported in the placebo group. Currently available information is insufficient to determine a causal relationship with the vaccine. There were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.
Participants 12 Through 15 Years of Age (2-Dose Primary Series)
In an analysis of Study 2, based on data up to the cutoff date of March 13, 2021, 2,260 participants (1,131 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA); 1,129 placebo) were 12 through 15 years of age. Of these, 1,308 (660 Pfizer-BioNTech COVID-19 Vaccine and 648 placebo) participants have been followed for at least 2 months after the second dose. The safety evaluation in Study 2 is ongoing.
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Overall, among the participants who received the Pfizer-BioNTech COVID-19 Vaccine, 50.1% were male and 49.9% were female, 85.9% were White, 4.6% were Black or African American, 11.7% were Hispanic/Latino, 6.4% were Asian, and 0.4% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
The mean duration of pain at the injection site after Dose 1 was 2.4 days (range 1 to 10 days), for redness 2.4 days (range 1 to 16 days), and for swelling 1.9 days (range 1 to 5 days) for participants in the Pfizer-BioNTech COVID-19 Vaccine group.
| Pfizer-BioNTech COVID-19 Vaccine † Dose 1 N ‡ =1127 n § (%) | Placebo Dose 1 N ‡ =1127 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 2 N ‡ =1097 n § (%) | Placebo Dose 2 N ‡ =1078 n § (%) | |
|---|---|---|---|---|
| Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | ||||
| ||||
| Redness ¶ | ||||
| Any (>2 cm) | 65 (5.8) | 12 (1.1) | 55 (5.0) | 10 (0.9) |
| Mild | 44 (3.9) | 11 (1.0) | 29 (2.6) | 8 (0.7) |
| Moderate | 20 (1.8) | 1 (0.1) | 26 (2.4) | 2 (0.2) |
| Severe | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Swelling ¶ | ||||
| Any (>2 cm) | 78 (6.9) | 11 (1.0) | 54 (4.9) | 6 (0.6) |
| Mild | 55 (4.9) | 9 (0.8) | 36 (3.3) | 4 (0.4) |
| Moderate | 23 (2.0) | 2 (0.2) | 18 (1.6) | 2 (0.2) |
| Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Pain at the injection site # | ||||
| Any | 971 (86.2) | 263 (23.3) | 866 (78.9) | 193 (17.9) |
| Mild | 467 (41.4) | 227 (20.1) | 466 (42.5) | 164 (15.2) |
| Moderate | 493 (43.7) | 36 (3.2) | 393 (35.8) | 29 (2.7) |
| Severe | 11 (1.0) | 0 (0.0) | 7 (0.6) | 0 (0.0) |
| Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. | ||||
| ||||
| Fever | ||||
| ≥38.0°C | 114 (10.1) | 12 (1.1) | 215 (19.6) | 7 (0.6) |
| ≥38.0°C to 38.4°C | 74 (6.6) | 8 (0.7) | 107 (9.8) | 5 (0.5) |
| >38.4°C to 38.9°C | 29 (2.6) | 2 (0.2) | 83 (7.6) | 1 (0.1) |
| >38.9°C to 40.0°C | 10 (0.9) | 2 (0.2) | 25 (2.3) | 1 (0.1) |
| >40.0°C | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Fatigue ¶ | ||||
| Any | 677 (60.1) | 457 (40.6) | 726 (66.2) | 264 (24.5) |
| Mild | 278 (24.7) | 250 (22.2) | 232 (21.1) | 133 (12.3) |
| Moderate | 384 (34.1) | 199 (17.7) | 468 (42.7) | 127 (11.8) |
| Severe | 15 (1.3) | 8 (0.7) | 26 (2.4) | 4 (0.4) |
| Headache ¶ | ||||
| Any | 623 (55.3) | 396 (35.1) | 708 (64.5) | 263 (24.4) |
| Mild | 361 (32.0) | 256 (22.7) | 302 (27.5) | 169 (15.7) |
| Moderate | 251 (22.3) | 131 (11.6) | 384 (35.0) | 93 (8.6) |
| Severe | 11 (1.0) | 9 (0.8) | 22 (2.0) | 1 (0.1) |
| Chills ¶ | ||||
| Any | 311 (27.6) | 109 (9.7) | 455 (41.5) | 73 (6.8) |
| Mild | 195 (17.3) | 82 (7.3) | 221 (20.1) | 52 (4.8) |
| Moderate | 111 (9.8) | 25 (2.2) | 214 (19.5) | 21 (1.9) |
| Severe | 5 (0.4) | 2 (0.2) | 20 (1.8) | 0 (0.0) |
| Vomiting # | ||||
| Any | 31 (2.8) | 10 (0.9) | 29 (2.6) | 12 (1.1) |
| Mild | 30 (2.7) | 8 (0.7) | 25 (2.3) | 11 (1.0) |
| Moderate | 0 (0.0) | 2 (0.2) | 4 (0.4) | 1 (0.1) |
| Severe | 1 (0.1) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Diarrhea Þ | ||||
| Any | 90 (8.0) | 82 (7.3) | 65 (5.9) | 43 (4.0) |
| Mild | 77 (6.8) | 72 (6.4) | 59 (5.4) | 38 (3.5) |
| Moderate | 13 (1.2) | 10 (0.9) | 6 (0.5) | 5 (0.5) |
| Severe | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| New or worsened muscle pain ¶ | ||||
| Any | 272 (24.1) | 148 (13.1) | 355 (32.4) | 90 (8.3) |
| Mild | 125 (11.1) | 88 (7.8) | 152 (13.9) | 51 (4.7) |
| Moderate | 145 (12.9) | 60 (5.3) | 197 (18.0) | 37 (3.4) |
| Severe | 2 (0.2) | 0 (0.0) | 6 (0.5) | 2 (0.2) |
| New or worsened joint pain ¶ | ||||
| Any | 109 (9.7) | 77 (6.8) | 173 (15.8) | 51 (4.7) |
| Mild | 66 (5.9) | 50 (4.4) | 91 (8.3) | 30 (2.8) |
| Moderate | 42 (3.7) | 27 (2.4) | 78 (7.1) | 21 (1.9) |
| Severe | 1 (0.1) | 0 (0.0) | 4 (0.4) | 0 (0.0) |
| Use of antipyretic or pain medication ß | 413 (36.6) | 111 (9.8) | 557 (50.8) | 95 (8.8) |
Unsolicited Adverse Events
In the following analyses of Study 2 in participants 12 through 15 years of age (1,131 of whom received Pfizer-BioNTech COVID-19 Vaccine and 1,129 of whom received placebo), 98.3% of study participants had at least 30 days of follow-up after Dose 2.
Serious Adverse Events
Serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 0.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.1% of placebo recipients. There were no notable patterns or numerical imbalances between treatment groups for specific categories of serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.
Non-Serious Adverse Events
Non-serious adverse events from Dose 1 through up to 30 days after Dose 2 in ongoing follow-up were reported by 5.8% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 5.8% of placebo recipients. From Dose 1 through 30 days after Dose 2, reports of lymphadenopathy plausibly related to the study intervention were imbalanced, with notably more cases in the Pfizer-BioNTech COVID-19 Vaccine group (7) vs. the placebo group (1). There were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.
Participants 5 Through 11 Years of Age (2-Dose Primary Series)
In an analysis of Study 3 Phase 2/3, based on data up to the cutoff date of September 06, 2021, 2,268 participants [1,518 Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA); 750 placebo] were 5 through 11 years of age. Of these, 2,158 (95.1%) [1,444 Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 714 placebo] participants have been followed for at least 2 months after the second dose. An analysis of Study 3 Phase 2/3 adverse event data also included another 2,379 participants [1,591 Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 788 placebo], of whom 71.2% had a follow-up period for at least 2 weeks after Dose 2 up to the cutoff date of October 8, 2021. The safety evaluation in Study 3 is ongoing.
Demographic characteristics in Study 3 were generally similar with regard to age, gender, race, and ethnicity among participants 5 through 11 years of age who received Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and those who received placebo. Among the 4,647 participants 5 through 11 years of age who received at least 1 dose of the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) or placebo, 51.8% were male and 48.2% were female, 77.3% were White, 5.8% were Black or African American, 16.9% were Hispanic/Latino, 8.3% were Asian, and 0.4% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
The mean duration of pain at the injection site after Dose 2 was 2.3 days (range 1 to 11 days), for redness 2.2 days (range 1 to 10 days), and for swelling 2.2 days (range 1 to 10 days) for children in the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) group up to the cutoff date of September 06, 2021.
| Pfizer-BioNTech COVID-19 Vaccine † Dose 1 N ‡ =1511 n § (%) | Placebo Dose 1 N ‡ , ¶ =748 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 2 N ‡ =1501 n § (%) | Placebo Dose 2 N ‡ , ¶ =740 n § (%) | |
|---|---|---|---|---|
| Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | ||||
| ||||
| Redness # | ||||
| Any (≥0.5 cm) | 222 (14.7) | 43 (5.7) | 278 (18.5) | 40 (5.4) |
| Mild | 143 (9.5) | 37 (4.9) | 143 (9.5) | 31 (4.2) |
| Moderate | 79 (5.2) | 6 (0.8) | 132 (8.8) | 9 (1.2) |
| Severe | 0 | 0 | 3 (0.2) | 0 |
| Swelling # | ||||
| Any (≥0.5 cm) | 158 (10.5) | 20 (2.7) | 229 (15.3) | 20 (2.7) |
| Mild | 85 (5.6) | 13 (1.7) | 117 (7.8) | 15 (2.0) |
| Moderate | 72 (4.8) | 7 (0.9) | 112 (7.5) | 5 (0.7) |
| Severe | 1 (0.1) | 0 | 0 | 0 |
| Pain at the injection site Þ | ||||
| Any | 1119 (74.1) | 234 (31.3) | 1065 (71.0) | 218 (29.5) |
| Mild | 890 (58.9) | 204 (27.3) | 793 (52.8) | 192 (25.9) |
| Moderate | 225 (14.9) | 30 (4.0) | 267 (17.8) | 26 (3.5) |
| Severe | 4 (0.3) | 0 | 5 (0.3) | 0 |
| Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose. | ||||
| ||||
| Fever | ||||
| ≥38.0℃ | 38 (2.5) | 10 (1.3) | 98 (6.5) | 9 (1.2) |
| ≥38.0℃ to 38.4℃ | 23 (1.5) | 4 (0.5) | 51 (3.4) | 5 (0.7) |
| >38.4℃ to 38.9℃ | 12 (0.8) | 5 (0.7) | 38 (2.5) | 3 (0.4) |
| >38.9℃ to 40.0℃ | 3 (0.2) | 1 (0.1) | 8 (0.5) | 1 (0.1) |
| >40.0℃ | 0 | 0 | 1 (0.1) | 0 |
| Fatigue # | ||||
| Any | 508 (33.6) | 234 (31.3) | 592 (39.4) | 180 (24.3) |
| Mild | 333 (22.0) | 150 (20.1) | 321 (21.4) | 96 (13.0) |
| Moderate | 171 (11.3) | 83 (11.1) | 260 (17.3) | 83 (11.2) |
| Severe | 4 (0.3) | 1 (0.1) | 11 (0.7) | 1 (0.1) |
| Headache # | ||||
| Any | 339 (22.4) | 180 (24.1) | 420 (28.0) | 138 (18.6) |
| Mild | 249 (16.5) | 131 (17.5) | 281 (18.7) | 93 (12.6) |
| Moderate | 88 (5.8) | 45 (6.0) | 136 (9.1) | 45 (6.1) |
| Severe | 2 (0.1) | 4 (0.5) | 3 (0.2) | 0 |
| Chills # | ||||
| Any | 70 (4.6) | 35 (4.7) | 147 (9.8) | 32 (4.3) |
| Mild | 54 (3.6) | 30 (4.0) | 105 (7.0) | 24 (3.2) |
| Moderate | 16 (1.1) | 5 (0.7) | 40 (2.7) | 7 (0.9) |
| Severe | 0 | 0 | 2 (0.1) | 1 (0.1) |
| Vomiting Þ | ||||
| Any | 33 (2.2) | 11 (1.5) | 28 (1.9) | 6 (0.8) |
| Mild | 26 (1.7) | 11 (1.5) | 27 (1.8) | 6 (0.8) |
| Moderate | 7 (0.5) | 0 | 1 (0.1) | 0 |
| Severe | 0 | 0 | 0 | 0 |
| Diarrhea ß | ||||
| Any | 89 (5.9) | 31 (4.1) | 79 (5.3) | 35 (4.7) |
| Mild | 79 (5.2) | 31 (4.1) | 72 (4.8) | 32 (4.3) |
| Moderate | 10 (0.7) | 0 | 7 (0.5) | 3 (0.4) |
| Severe | 0 | 0 | 0 | 0 |
| New or worsened muscle pain # | ||||
| Any | 137 (9.1) | 51 (6.8) | 175 (11.7) | 55 (7.4) |
| Mild | 96 (6.4) | 35 (4.7) | 116 (7.7) | 38 (5.1) |
| Moderate | 40 (2.6) | 16 (2.1) | 58 (3.9) | 17 (2.3) |
| Severe | 1 (0.1) | 0 | 1 (0.1) | 0 |
| New or worsened joint pain # | ||||
| Any | 50 (3.3) | 41 (5.5) | 78 (5.2) | 27 (3.6) |
| Mild | 34 (2.3) | 31 (4.1) | 57 (3.8) | 20 (2.7) |
| Moderate | 16 (1.1) | 10 (1.3) | 21 (1.4) | 7 (0.9) |
| Severe | 0 | 0 | 0 | 0 |
| Use of antipyretic or pain medication à | 217 (14.4) | 62 (8.3) | 296 (19.7) | 60 (8.1) |
Unsolicited Adverse Events
In the following analyses of Study 3 in children 5 through 11 years of age (1,518 of whom received Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) and 750 of whom received placebo), 99.5% of participants had at least 30 days of follow-up after Dose 2.
Serious Adverse Events
In 1 group of participants (initial enrollment cohort) with a median of 2.3 months follow-up post Dose 2, no serious adverse events were reported that were considered related to vaccination. In a second group of participants (expansion cohort) with a median of 2.4 weeks follow-up post Dose 2, no serious adverse events were reported that were considered related to vaccination.
Non-Serious Adverse Events
In 1 group of participants (initial enrollment cohort), non-serious adverse events from Dose 1 through up to 30 days after Dose 2 up to the cutoff date of September 06, 2021, in ongoing follow-up were reported by 10.9% of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) recipients and by 9.1% of placebo recipients. In this group of participants, >99% had follow-up 30 days post Dose 2. In a second group of participants (expansion cohort) for which the median follow-up was 2.4 weeks (range 0 to 3.7 weeks), non-serious adverse events from Dose 1 through the cutoff date of October 08, 2021, were reported by 7.1% of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) recipients and by 6.3% of placebo recipients.
In the initial enrollment cohort, from Dose 1 through 30 days after Dose 2, lymphadenopathy was reported in 13 (0.9%) participants in the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) group vs. 1 (0.1%) in the placebo group. In the expansion cohort from Dose 1 through the cutoff date, lymphadenopathy was reported in 6 (0.4%) participants in the Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) group vs. 3 (0.4%) in the placebo group. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.
Participants 2 Through 4 Years of Age (3-Dose Primary Series)
In an analysis of Study 3 (Phase 2/3), based on data in the blinded placebo-controlled follow-up period up to the cutoff date of April 29, 2022, 886 participants 2 through 4 years of age who received a 3-dose primary series [606 Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA); 280 placebo] have been followed a median of 1.4 months after the third dose.
Demographic characteristics in Study 3 were generally similar with regard to age, gender, race, and ethnicity among participants 2 through 4 years of age who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Among the 1,835 participants 2 through 4 years of age who received at least 1 dose of the Pfizer-BioNTech COVID-19 Vaccine, 49.1% were male and 50.9% were female, 80.1% were White, 14.4% were Hispanic/Latino, 7.1% were multi-racial, 6.9% were Asian, 5.1% were Black or African American, and 0.2% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
The mean duration of pain at the injection site after Dose 3 was 1.7 days (range 1 to 14 days), for redness 1.5 days (range 1 to 3 days), and for swelling 1.8 days (range 1 to 4 days) for participants 2 through 4 years of age in the Pfizer-BioNTech COVID-19 Vaccine group in the blinded placebo-controlled follow-up period (cutoff date of April 29, 2022).
| Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | ||||||
| ||||||
| Pfizer-BioNTech COVID-19 Vaccine † Dose 1 N ‡ =1814 to 1825 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 2 N ‡ =1772 to 1779 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 3 N ‡ =547 to 552 n § (%) | ||||
| Redness ¶ | ||||||
| Any (≥0.5 cm) | 160 (8.8) | 77 (8.5) | 202 (11.4) | 50 (5.7) | 60 (10.9) | 9 (3.4) |
| Mild | 137 (7.5) | 67 (7.4) | 170 (9.6) | 43 (4.9) | 53 (9.6) | 7 (2.7) |
| Moderate | 22 (1.2) | 9 (1.0) | 31 (1.7) | 7 (0.8) | 7 (1.3) | 2 (0.8) |
| Severe | 1 (0.1) | 1 (0.1) | 1 (0.1) | 0 | 0 | 0 |
| Swelling ¶ | ||||||
| Any (≥0.5 cm) | 67 (3.7) | 26 (2.9) | 102 (5.7) | 18 (2.1) | 17 (3.1) | 3 (1.1) |
| Mild | 59 (3.2) | 21 (2.3) | 81 (4.6) | 16 (1.8) | 16 (2.9) | 3 (1.1) |
| Moderate | 8 (0.4) | 5 (0.6) | 21 (1.2) | 2 (0.2) | 1 (0.2) | 0 |
| Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Pain at the injection site # | ||||||
| Any | 559 (30.8) | 186 (20.6) | 550 (31.0) | 178 (20.3) | 146 (26.7) | 35 (13.4) |
| Mild | 522 (28.8) | 178 (19.7) | 514 (29.0) | 169 (19.3) | 130 (23.8) | 33 (12.6) |
| Moderate | 37 (2.0) | 7 (0.8) | 36 (2.0) | 8 (0.9) | 16 (2.9) | 2 (0.8) |
| Severe | 0 | 1 (0.1) | 0 | 1 (0.1) | 0 | 0 |
| Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose. | ||||||
| ||||||
| Pfizer-BioNTech COVID-19 Vaccine † Dose 1 N ‡ =1813 to 1824 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 2 N ‡ =1772 to 1779 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 3 N ‡ =547 to 552 n § (%) | ||||
| Fever | ||||||
| ≥38.0℃ | 95 (5.2) | 48 (5.3) | 88 (4.9) | 46 (5.2) | 28 (5.1) | 11 (4.2) |
| ≥38.0℃ to 38.4℃ | 57 (3.1) | 24 (2.6) | 41 (2.3) | 17 (1.9) | 16 (2.9) | 4 (1.5) |
| >38.4℃ to 38.9℃ | 24 (1.3) | 16 (1.8) | 26 (1.5) | 21 (2.4) | 8 (1.4) | 4 (1.5) |
| >38.9℃ to 40.0℃ | 13 (0.7) | 8 (0.9) | 19 (1.1) | 8 (0.9) | 4 (0.7) | 3 (1.1) |
| >40.0℃ | 1 (0.1) | 0 | 2 (0.1) | 0 | 0 | 0 |
| Fatigue ¶ | ||||||
| Any | 539 (29.7) | 277 (30.6) | 456 (25.7) | 201 (22.9) | 134 (24.5) | 57 (21.8) |
| Mild | 335 (18.5) | 176 (19.4) | 267 (15.1) | 120 (13.7) | 87 (15.9) | 35 (13.4) |
| Moderate | 198 (10.9) | 96 (10.6) | 181 (10.2) | 78 (8.9) | 45 (8.2) | 22 (8.4) |
| Severe | 6 (0.3) | 5 (0.6) | 8 (0.5) | 3 (0.3) | 2 (0.4) | 0 |
| Headache ¶ | ||||||
| Any | 81 (4.5) | 44 (4.9) | 81 (4.6) | 36 (4.1) | 27 (4.9) | 11 (4.2) |
| Mild | 63 (3.5) | 35 (3.9) | 63 (3.6) | 23 (2.6) | 19 (3.5) | 10 (3.8) |
| Moderate | 18 (1.0) | 8 (0.9) | 18 (1.0) | 12 (1.4) | 8 (1.5) | 1 (0.4) |
| Severe | 0 | 1 (0.1) | 0 | 1 (0.1) | 0 | 0 |
| Chills ¶ | ||||||
| Any | 41 (2.3) | 22 (2.4) | 53 (3.0) | 23 (2.6) | 18 (3.3) | 7 (2.7) |
| Mild | 28 (1.5) | 16 (1.8) | 35 (2.0) | 17 (1.9) | 14 (2.6) | 7 (2.7) |
| Moderate | 10 (0.6) | 6 (0.7) | 18 (1.0) | 6 (0.7) | 3 (0.5) | 0 |
| Severe | 3 (0.2) | 0 | 0 | 0 | 1 (0.2) | 0 |
| Vomiting # | ||||||
| Any | 54 (3.0) | 24 (2.7) | 61 (3.4) | 29 (3.3) | 9 (1.6) | 10 (3.8) |
| Mild | 44 (2.4) | 14 (1.5) | 55 (3.1) | 26 (3.0) | 7 (1.3) | 9 (3.4) |
| Moderate | 10 (0.6) | 10 (1.1) | 6 (0.3) | 3 (0.3) | 2 (0.4) | 1 (0.4) |
| Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Diarrhea Þ | ||||||
| Any | 139 (7.7) | 72 (8.0) | 118 (6.7) | 64 (7.3) | 28 (5.1) | 13 (5.0) |
| Mild | 130 (7.2) | 64 (7.1) | 105 (5.9) | 57 (6.5) | 21 (3.8) | 10 (3.8) |
| Moderate | 9 (0.5) | 8 (0.9) | 12 (0.7) | 7 (0.8) | 7 (1.3) | 3 (1.1) |
| Severe | 0 | 0 | 1 (0.1) | 0 | 0 | 0 |
| New or worsened muscle pain ¶ | ||||||
| Any | 43 (2.4) | 15 (1.7) | 46 (2.6) | 21 (2.4) | 11 (2.0) | 4 (1.5) |
| Mild | 33 (1.8) | 13 (1.4) | 33 (1.9) | 17 (1.9) | 8 (1.5) | 4 (1.5) |
| Moderate | 9 (0.5) | 2 (0.2) | 13 (0.7) | 4 (0.5) | 3 (0.5) | 0 |
| Severe | 1 (0.1) | 0 | 0 | 0 | 0 | 0 |
| New or worsened joint pain ¶ | ||||||
| Any | 14 (0.8) | 18 (2.0) | 24 (1.4) | 9 (1.0) | 7 (1.3) | 2 (0.8) |
| Mild | 12 (0.7) | 13 (1.4) | 18 (1.0) | 6 (0.7) | 5 (0.9) | 2 (0.8) |
| Moderate | 2 (0.1) | 5 (0.6) | 6 (0.3) | 3 (0.3) | 1 (0.2) | 0 |
| Severe | 0 | 0 | 0 | 0 | 1 (0.2) | 0 |
| Use of antipyretic or pain medication ß | 197 (10.8) | 83 (9.1) | 177 (9.9) | 74 (8.4) | 47 (8.5) | 18 (6.9) |
Unsolicited Adverse Events
In the following analyses of Study 3 in participants 2 through 4 years of age (606 of whom received Pfizer-BioNTech COVID-19 Vaccine and 280 of whom received placebo), 76.6% of participants had at least 30 days of follow-up after Dose 3.
Serious Adverse Events
Serious adverse events from Dose 1 through 1 month after Dose 3, with an overall median of 1.4 months follow-up after Dose 3 were reported by 0.7% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 0.9% of placebo recipients. One serious adverse event of fever (maximum temperature 40.3°C) on Day 3 after Dose 2 in a 4-year-old was considered possibly related to vaccination.
Non-Serious Adverse Events
Non-serious adverse events from Dose 1 through up to 30 days after Dose 3, in ongoing follow-up were reported by 18.5% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 18.5% of placebo recipients.
From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 1 (0.1%) participant in the Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) group vs. 0 (0.0%) in the placebo group. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.
Participants 6 Through 23 Months of Age (3-Dose Primary Series)
In an analysis of Study 3 (Phase 2/3), based on data in the blinded placebo-controlled follow-up period up to the cutoff date of April 29, 2022, 570 participants 6 through 23 months of age who received a 3-dose primary series [386 Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA); 184 placebo] have been followed for a median of 1.3 months after the third dose.
Demographic characteristics in Study 3 were generally similar with regard to age, gender, race, and ethnicity among participants 6 through 23 months of age who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Among the 1,178 participants 6 through 23 months of age who received at least 1 dose of the Pfizer-BioNTech COVID-19 Vaccine, 50.0% were male and 50.0% were female, 78.3% were White, 9.9% were multi-racial, 13.7% were Hispanic/Latino, 7.7% were Asian, 3.6% were Black or African American, and 0.3% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
The mean duration of tenderness at the injection site after Dose 3 was 1.5 days (range 1 to 9 days), for redness 1.5 days (range 1 to 5 days), and for swelling 1.8 days (range 1 to 3 days) for participants 6 through 23 months of age in the Pfizer-BioNTech COVID-19 Vaccine group in the blinded placebo-controlled follow-up period (cutoff date of April 29, 2022).
| Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | ||||||
| ||||||
| Pfizer-BioNTech COVID-19 Vaccine † Dose 1 N ‡ =1159 to 1173 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 2 N ‡ =1137 to 1147 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 3 N ‡ =362 to 365 n § (%) | ||||
| Redness ¶ | ||||||
| Any (≥0.5 cm) | 124 (10.6) | 44 (7.4) | 107 (9.3) | 39 (6.6) | 26 (7.1) | 9 (5.3) |
| Mild | 114 (9.7) | 41 (6.9) | 97 (8.5) | 36 (6.1) | 17 (4.7) | 8 (4.7) |
| Moderate | 10 (0.9) | 3 (0.5) | 10 (0.9) | 3 (0.5) | 8 (2.2) | 1 (0.6) |
| Severe | 0 | 0 | 0 | 0 | 1 (0.3) | 0 |
| Swelling ¶ | ||||||
| Any (≥0.5 cm) | 46 (3.9) | 15 (2.5) | 45 (3.9) | 9 (1.5) | 10 (2.7) | 3 (1.8) |
| Mild | 40 (3.4) | 13 (2.2) | 39 (3.4) | 8 (1.4) | 7 (1.9) | 3 (1.8) |
| Moderate | 6 (0.5) | 2 (0.3) | 6 (0.5) | 1 (0.2) | 3 (0.8) | 0 |
| Severe | 0 | 0 | 0 | 0 | 0 | 0 |
| Tenderness at the injection site # | ||||||
| Any | 192 (16.6) | 66 (11.2) | 171 (15.0) | 50 (8.5) | 58 (16.0) | 20 (11.8) |
| Mild | 181 (15.6) | 61 (10.3) | 154 (13.5) | 42 (7.1) | 51 (14.1) | 17 (10.0) |
| Moderate | 11 (0.9) | 5 (0.8) | 16 (1.4) | 8 (1.4) | 7 (1.9) | 3 (1.8) |
| Severe | 0 | 0 | 1 (0.1) | 0 | 0 | 0 |
| Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose. | ||||||
| ||||||
| Pfizer-BioNTech COVID-19 Vaccine † Dose 1 N ‡ =1159 to 1173 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 2 N ‡ =1137 to 1147 n § (%) | Pfizer-BioNTech COVID-19 Vaccine † Dose 3 N ‡ =362 to 365 n § (%) | ||||
| Fever | ||||||
| ≥38.0℃ | 85 (7.2) | 43 (7.2) | 85 (7.4) | 36 (6.1) | 25 (6.8) | 10 (5.9) |
| ≥38.0℃ to 38.4℃ | 42 (3.6) | 22 (3.7) | 41 (3.6) | 18 (3.0) | 14 (3.8) | 7 (4.1) |
| >38.4℃ to 38.9℃ | 23 (2.0) | 14 (2.4) | 20 (1.7) | 11 (1.9) | 5 (1.4) | 2 (1.2) |
| >38.9℃ to 40.0℃ | 19 (1.6) | 6 (1.0) | 23 (2.0) | 7 (1.2) | 5 (1.4) | 1 (0.6) |
| >40.0℃ | 1 (0.1) | 1 (0.2) | 1 (0.1) | 0 | 1 (0.3) | 0 |
| Decreased appetite ¶ | ||||||
| Any | 257 (22.2) | 125 (21.2) | 252 (22.2) | 106 (18.0) | 73 (20.2) | 23 (13.5) |
| Mild | 138 (11.9) | 73 (12.4) | 157 (13.8) | 63 (10.7) | 42 (11.6) | 13 (7.6) |
| Moderate | 116 (10.0) | 51 (8.6) | 91 (8.0) | 42 (7.1) | 27 (7.5) | 10 (5.9) |
| Severe | 3 (0.3) | 1 (0.2) | 4 (0.4) | 1 (0.2) | 4 (1.1) | 0 |
| Drowsiness # | ||||||
| Any | 313 (27.0) | 173 (29.3) | 271 (23.8) | 125 (21.2) | 72 (19.9) | 22 (12.9) |
| Mild | 251 (21.7) | 130 (22.0) | 201 (17.7) | 98 (16.6) | 50 (13.8) | 15 (8.8) |
| Moderate | 60 (5.2) | 41 (6.9) | 66 (5.8) | 26 (4.4) | 21 (5.8) | 6 (3.5) |
| Severe | 2 (0.2) | 2 (0.3) | 4 (0.4) | 1 (0.2) | 1 (0.3) | 1 (0.6) |
| Irritability Þ | ||||||
| Any | 593 (51.2) | 279 (47.2) | 539 (47.4) | 240 (40.7) | 158 (43.6) | 64 (37.6) |
| Mild | 245 (21.1) | 106 (17.9) | 213 (18.7) | 89 (15.1) | 56 (15.5) | 27 (15.9) |
| Moderate | 341 (29.4) | 173 (29.3) | 319 (28.1) | 146 (24.7) | 101 (27.9) | 37 (21.8) |
| Severe | 7 (0.6) | 0 | 7 (0.6) | 5 (0.8) | 1 (0.3) | 0 |
| Use of antipyretic or pain medication ß | 281 (24.0) | 117 (19.7) | 243 (21.2) | 111 (18.8) | 70 (19.2) | 28 (16.5) |
Unsolicited Adverse Events
In the following analyses of Study 3 in participants 6 through 23 months of age (386 of whom received Pfizer-BioNTech COVID-19 Vaccine and 184 of whom received placebo), 83.7% of participants had at least 30 days of follow-up after Dose 3.
Serious Adverse Events
Serious adverse events from Dose 1 through 1 month after Dose 3, with an overall median of 1.3 months follow-up after Dose 3 were reported by 1.4% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 2.3% of placebo recipients. No serious adverse events were reported that were considered related to vaccination.
Non-Serious Adverse Events
Non-serious adverse events from Dose 1 through up to 1 month after Dose 3, in ongoing follow-up were reported by 29.1% of Pfizer-BioNTech COVID-19 Vaccine recipients and by 26.3% of placebo recipients.
From Dose 1 through 30 days after Dose 3, lymphadenopathy was reported in 2 (0.2%) participants in the Pfizer-BioNTech COVID-19 Vaccine group vs. 0 (0%) in the placebo group. There were no other notable patterns between treatment groups for specific categories of non-serious adverse events that would suggest a causal relationship to Pfizer-BioNTech COVID-19 Vaccine.
Third Primary Series Dose in Individuals with Certain Kinds of Immunocompromise
From an independent report (Kamar N, Abravanel F, Marion O, et al. Three doses of an mRNA Covid-19 vaccine in solid-organ transplant recipients. N Engl J Med) , in 99 individuals who had undergone various solid organ transplant procedures (heart, kidney, liver, lung, pancreas) 97±8 months previously who received a third vaccine dose, the adverse event profile was similar to that after the second dose and no grade 3 or grade 4 events were reported in recipients who were followed for 1 month following post Dose 3.
Pfizer-BioNTech COVID-19 Vaccine Administered as a First Booster Dose Following a Primary Series of Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA) in Participants 18 through 55 Years of Age
A subset of Study 2 Phase 2/3 participants of 306 participants 18 through 55 years of age received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) approximately 6 months (range of 4.8 to 8.0 months) after completing the primary series. Additionally, a total of 23 Study 2 (Phase 1) participants (11 participants 18 through 55 years of age and 12 participants 65 through 85 years of age) received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine approximately 8 months (range 7.9 to 8.8 months) after completing the primary series. Participants were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination in an electronic diary. Participants are being monitored for unsolicited adverse events through 1 month after vaccination and for serious adverse events for 6 months after the last vaccination.
Among the 306 Phase 2/3 participants, the median age was 42 years (range 19 through 55 years of age), 45.8% were male and 54.2% were female, 81.4% were White, 27.8% were Hispanic/Latino, 9.2% were Black or African American, 5.2% were Asian, and 0.7% were American Indian/Alaska Native. Among the 12 Phase 1 participants 65 through 85 years of age, the median age was 69 years (range 65 through 75 years of age), 6 were male and all were White and Not Hispanic/Latino. Following the booster dose, the median follow-up time was 2.6 months (range 2.1 to 2.9 months) for Phase 1 participants and 2.6 months (range 1.1 to 2.8 months) for Phase 2/3 participants.
Solicited Local and Systemic Adverse Reactions
Table 13 and Table 14 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of a first booster dose with Pfizer-BioNTech COVID-19 Vaccine for Phase 2/3 participants 18 through 55 years of age.
In participants who received a first booster dose, the mean duration of pain at the injection site was 2.6 days (range 1 to 8 days), for redness 2.2 days (range 1 to 15 days), and for swelling 2.2 days (range 1 to 8 days).
| Solicited Local Adverse Reaction | Pfizer-BioNTech COVID-19 Vaccine † First Booster Dose N ‡ = 289 n § (%) |
|---|---|
| Note: Adverse Reactions were collected in the electronic diary (e-diary) from day of vaccination (Day 1) to Day 7 after the booster dose.Note: No Grade 4 solicited local adverse reactions were reported. | |
| |
| Redness ¶ | |
| Any (>2 cm) | 17 (5.9) |
| Mild | 10 (3.5) |
| Moderate | 7 (2.4) |
| Severe | 0 |
| Swelling ¶ | |
| Any (>2 cm) | 23 (8.0) |
| Mild | 13 (4.5) |
| Moderate | 9 (3.1) |
| Severe | 1 (0.3) |
| Pain at the injection site # | |
| Any | 240 (83.0) |
| Mild | 174 (60.2) |
| Moderate | 65 (22.5) |
| Severe | 1 (0.3) |
| Solicited Systemic Adverse Reaction | Pfizer-BioNTech COVID-19 Vaccine † First Booster Dose N ‡ = 289 n § (%) |
|---|---|
| Note: Adverse reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from day of vaccination (Day 1) to Day 7 after the booster dose.Note: No Grade 4 solicited systemic adverse reactions were reported. | |
| |
| Fever | |
| ≥38.0°C | 25 (8.7) |
| ≥38.0°C to 38.4°C | 12 (4.2) |
| >38.4°C to 38.9°C | 12 (4.2) |
| >38.9°C to 40.0°C | 1 (0.3) |
| >40.0°C | 0 |
| Fatigue ¶ | |
| Any | 184 (63.7) |
| Mild | 68 (23.5) |
| Moderate | 103 (35.6) |
| Severe | 13 (4.5) |
| Headache ¶ | |
| Any | 140 (48.4) |
| Mild | 83 (28.7) |
| Moderate | 54 (18.7) |
| Severe | 3 (1.0) |
| Chills ¶ | |
| Any | 84 (29.1) |
| Mild | 37 (12.8) |
| Moderate | 44 (15.2) |
| Severe | 3 (1.0) |
| Vomiting # | |
| Any | 5 (1.7) |
| Mild | 5 (1.7) |
| Moderate | 0 |
| Severe | 0 |
| Diarrhea Þ | |
| Any | 25 (8.7) |
| Mild | 21 (7.3) |
| Moderate | 4 (1.4) |
| Severe | 0 |
| New or worsened muscle pain ¶ | |
| Any | 113 (39.1) |
| Mild | 52 (18.0) |
| Moderate | 57 (19.7) |
| Severe | 4 (1.4) |
| New or worsened joint pain ¶ | |
| Any | 73 (25.3) |
| Mild | 36 (12.5) |
| Moderate | 36 (12.5) |
| Severe | 1 (0.3) |
| Use of antipyretic or pain medication ß | 135 (46.7) |
In Phase 1 participants ≥65 years of age (n=12), local reaction pain at the injection site (n=8, 66.7%) and systemic reactions fatigue (n=5, 41.7%), headache (n=5, 41.7%), chills (n=2, 16.7%), muscle pain (n=4, 33.3%), and joint pain (n=2, 16.7%) were reported after the booster dose. No participant in this age group reported a severe systemic event or fever after the booster dose.
Unsolicited Adverse Events
Overall, the 306 participants who received a first booster dose, had a median follow-up time of 2.6 months after the booster dose to the cutoff date (June 17, 2021).
In an analysis of all unsolicited adverse events reported following the first booster dose, through 1 month after the booster dose, in participants 18 through 55 years of age (N=306), those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (n=16, 5.2%), nausea (n=2, 0.7%), decreased appetite (n=1, 0.3%), rash (n=1, 0.3%), and pain in extremity (n=1, 0.3%).
Serious Adverse Events
Of the 306 participants who received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine, there were no serious adverse events reported from the booster dose through 30 days after the booster dose. One participant reported a serious adverse event 61 days after the booster dose that was assessed as unrelated to vaccination.
First Booster Dose Following a Primary Series of Pfizer-BioNTech COVID-19 in Participants 5 Through 11 Years of Age
A subset of Phase 2/3 participants 5 through 11 years of age received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) at least 5 months after completing the primary series (range 5 to 9 months, 86.8% of participants received a booster dose at least 8 months after Dose 2). Those participants vaccinated prior to February 22, 2022 provided the safety database (n=401), and had a median safety follow-up of 1.3 months from vaccination through the data cutoff date of March 22, 2022.
The median age of these 401 participants was 8.0 years (range 5 through 11 years of age), 52.4% were male and 47.6% were female, 70.1% were White, 7.2% were Black or African American, 22.9% were Hispanic/Latino, 7.7% were Asian, and 2.0% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
Table 15 and Table 16 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of a booster dose of Pfizer-BioNTech COVID-19 Vaccine for Phase 2/3 participants 5 through 11 years of age.
In participants who received a booster dose, the mean duration of pain at the injection site after the booster dose was 2.4 days (range 1 to 35 days), for redness 2.3 days (range 1 to 12 days), and for swelling 2.3 days (range 1 to 9 days).
| Pfizer-BioNTech COVID-19 Vaccine † Booster N ‡ =371 n § (%) | |
|---|---|
| Note: Reactions were collected in the e-diary and unscheduled clinical assessments from Day 1 through Day 7 after vaccination. | |
| |
| Redness ¶ | |
| Any (≥0.5 cm) | 58 (15.6) |
| Mild | 38 (10.2) |
| Moderate | 19 (5.1) |
| Severe | 1 (0.3) |
| Swelling ¶ | |
| Any (≥0.5 cm) | 61 (16.4) |
| Mild | 30 (8.1) |
| Moderate | 31 (8.4) |
| Severe | 0 |
| Pain at the injection site # | |
| Any | 274 (73.9) |
| Mild | 177 (47.7) |
| Moderate | 95 (25.6) |
| Severe | 2 (0.5) |
| Note: Events and use of antipyretic or pain medication were collected in the e-diary and unscheduled clinical assessments from Day 1 through Day 7 after vaccination. | |
| |
| Solicited Systemic Reaction | |
| Fever | |
| ≥38.0°C | 25 (6.7) |
| ≥38.0°C to 38.4°C | 17 (4.6) |
| >38.4°C to 38.9°C | 5 (1.3) |
| >38.9°C to 40.0°C | 3 (0.8) |
| >40.0°C | 0 |
| Fatigue ¶ | |
| Any | 169 (45.6) |
| Mild | 99 (26.7) |
| Moderate | 63 (17.0) |
| Severe | 7 (1.9) |
| Headache ¶ | |
| Any | 126 (34.0) |
| Mild | 76 (20.5) |
| Moderate | 47 (12.7) |
| Severe | 0 |
| Chills ¶ | |
| Any | 39 (10.5) |
| Mild | 23 (6.2) |
| Moderate | 15 (4.0) |
| Severe | 1 (0.3) |
| Vomiting # | |
| Any | 9 (2.4) |
| Mild | 6 (1.6) |
| Moderate | 3 (0.8) |
| Severe | 0 |
| Diarrhea Þ | |
| Any | 18 (4.9) |
| Mild | 15 (4.0) |
| Moderate | 2 (0.5) |
| Severe | 1 (0.3) |
| New or worsened muscle pain ¶ | |
| Any | 68 (18.3) |
| Mild | 40 (10.8) |
| Moderate | 28 (7.5) |
| Severe | 0 |
| New or worsened joint pain ¶ | |
| Any | 25 (6.7) |
| Mild | 14 (3.8) |
| Moderate | 11 (3.0) |
| Severe | 0 |
| Use of antipyretic or pain medication ß | 114 (30.7) |
Unsolicited Adverse Events
Overall, the 401 participants who received a first booster dose of Pfizer-BioNTech COVID-19 Vaccine had a median follow-up time of 1.3 months after the booster dose through the cutoff date.
In an analysis of all unsolicited adverse events reported in participants 5 through 11 years of age (N=401) through up to 1 month after a first booster dose, lymphadenopathy (n=10, 2.5%) was an adverse reaction not already captured by solicited local and systemic reactions.
Serious Adverse Events
No serious adverse events were reported after the first booster dose through the cutoff date.
Pfizer-BioNTech COVID-19 Vaccine Administered as a First Booster Dose Following Vaccination with Another Authorized or Approved COVID-19 Vaccine
The safety of a Pfizer-BioNTech COVID-19 Vaccine booster dose in individuals who completed primary vaccination with another authorized or approved COVID-19 Vaccine (heterologous booster dose) is inferred from the safety of a Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) booster dose administered following completion of Pfizer-BioNTech COVID-19 Vaccine primary series (homologous booster dose) and from data from an independent National Institutes of Health (NIH) study Phase 1/2 open-label clinical trial (NCT04889209) conducted in the United States that evaluated a heterologous booster dose of the Pfizer-BioNTech COVID-19 Vaccine. In this study, participants who had completed primary vaccination with a Moderna COVID-19 Vaccine 2-dose series (N=151), a Janssen COVID-19 Vaccine single dose (N=156), or a Pfizer-BioNTech COVID-19 Vaccine 2-dose series (N=151) at least 12 weeks prior to enrollment and who reported no history of SARS-CoV-2 infection were randomized 1:1:1 to receive a booster dose of 1 of 3 vaccines: Moderna COVID-19 Vaccine, Janssen COVID-19 Vaccine, or Pfizer-BioNTech COVID-19 Vaccine. Adverse events were assessed through 28 days after the booster dose. An overall review of adverse reactions reported in the study following the Pfizer-BioNTech COVID-19 Vaccine heterologous booster dose did not identify any new safety concerns, as compared with adverse reactions reported following a Pfizer-BioNTech COVID-19 Vaccine primary series doses or homologous booster dose.
Pfizer-BioNTech COVID-19 Vaccine Administered as a Second Booster Dose Following Primary and Booster Vaccination with Another Authorized or Approved COVID-19 Vaccine
Safety surveillance data from the Ministry of Health of Israel on the administration of approximately 700,000 fourth doses of the Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) given at least 4 months after the third dose in participants 18 years of age and older (approximately 600,000 of whom were 60 years of age and older) revealed no new safety concerns.
Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
Study 5 (NCT05472038) enrolled participants 12 years of age and older to receive a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent (30 mcg modRNA). In Study 5, all participants 12 years of age and older are being monitored for safety throughout the study [through 6 months after the booster (fourth dose)].
Study 6 (NCT05543616) enrolled participants 6 months through 11 years of age to receive a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
In Study 6, all participants 6 months through 4 years of age were monitored for solicited local and systemic reactions and use of antipyretic medication after the vaccination in an electronic diary. Participants are being monitored for safety throughout the study [through 6 months after the booster (fourth dose)]. Tables 17 through 20 present the frequency and severity of solicited local and systemic reactions, within 7 days following a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent in participants 6 through 23 months of age and 2 through 4 years of age who were previously vaccinated with a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine.
Participants 12 Years of Age and Older Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
A subset of Study 5 Phase 2/3 participants 12 through 17 years of age (n=107), 18 through 55 years of age (n=103) and 56 years of age and older (n=106) previously vaccinated with a 2-dose primary series and 1 booster dose of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA), received a second booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (30 mcg modRNA).
The participants received the second booster dose a median of 9.9 months (range 5.5 to 14.3 months) after receiving the first booster dose and had a median follow-up time of 1.6 months up to a data cutoff date of October 12, 2022. The median age was 40.0 years, 53.2% were male, 46.8% were female, 81.3% were White, 9.2% were Hispanic/Latino, 5.1% were Asian, and 10.8% were Black or African American.
Unsolicited Adverse Events
In the following analysis of Study 5, 316 participants 12 years of age and older who received a second booster of Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.6 months (range 1.3 to 1.8 months) to the cutoff date October 12, 2022.
Serious Adverse Events
Serious adverse events were reported in the 1 participant (considered unrelated to the vaccine) from the study vaccination through 1 month post vaccination.
Non-Serious Adverse Events
Lymphadenopathy 2 days post-vaccination, considered related to vaccination, was reported in 1 (0.3%) participant 12 years of age and older.
Participants 5 Through 11 Years of Age Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
In Study 6, 113 participants 5 through 11 years of age previously vaccinated with a 2-dose primary series and 1 booster dose of Pfizer-BioNTech COVID-19 Vaccine (10 mcg modRNA) received a booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (10 mcg modRNA).
Participants received a booster (fourth dose) with Pfizer-BioNTech COVID-19, Bivalent 2.6 to 8.5 months after receiving their third dose with Pfizer-BioNTech COVID-19 Vaccine and had a median follow-up time of 1.6 months (range 1.1 to 2.3 months) up to a data cutoff date of November 25, 2022. Their median age was 9 years (range 5 through 11 years of age), 50.4% were male and 49.6% were female, 58.4% were White, 20.4% were Hispanic/Latino, 19.5% were multi-racial, 11.5% were Asian, and 8.0% were Black or African American.
Unsolicited Adverse Events
In the following analysis of Study 6, 113 participants 5 through 11 years of age who received a booster (fourth dose) with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.6 months (range 1.1 to 2.3 months) to the cutoff date (November 25, 2022).
Serious Adverse Events
No serious adverse events were reported in the 113 participants 5 through 11 years of age from the study vaccination through 1 month post vaccination.
Non-Serious Adverse Events
Lymphadenopathy 2 days post-vaccination, considered related to vaccination, was reported in 1 (0.9%) participant 5 through 11 years of age.
Participants 2 Through 4 Years of Age Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
In a subset of Study 6, 36 participants 2 through 4 years of age previously vaccinated with a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) received a booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (3 mcg modRNA).
Participants received a booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent 2.2 to 8.5 months after receiving their third dose with Pfizer-BioNTech COVID-19 Vaccine and had a median follow-up time of 1.9 months (range 1.6 to 2.3 months) up to a data cutoff date of November 25, 2022. Their median age was 2 years (range 2 through 4 years of age), 55.6% were male and 44.4% were female, 61.1% were White, 30.6% were Hispanic/Latino, 22.2% were multi-racial, 11.1% were Asian, and 5.6% were Black or African American.
Solicited Local and Systemic Adverse Reactions
Table 17 and Table 18 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
The mean duration of pain at the injection site was 1.1 days (range 1 to 2 days), for redness 1.3 days (range 1 to 2 days), and for swelling 3 days for participants 2 through 4 years of age.
Table 17: Local Adverse Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 2 through 4 Years of Age – Safety Population
| Note: Reactions were collected in the electronic diary (e-diary) and at unscheduled clinical assessments from Day 1 through Day 7 after the study vaccination. Reactions reported as adverse events in the case report form within 7 days after the study vaccination were also included in the analysis; the severity of these events is based on the grading scale in the adverse event section of the case report form. | |
| |
| Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) 3 mcg modRNA N * =36 n † (%) | |
| Redness ‡ | |
| Any (≥0.5 cm) | 3 (8.3) |
| Mild | 2 (5.6) |
| Moderate | 1 (2.8) |
| Swelling ‡ | |
| Any (≥0.5 cm) | 1 (2.8) |
| Mild | 0 |
| Moderate | 1 (2.8) |
| Pain at the injection site § | |
| Any | 10 (27.8) |
| Mild | 8 (22.2) |
| Moderate | 2 (5.6) |
Table 18: Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 2 Through 4 Years of Age – Safety Population
| Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) and at unscheduled clinical assessments from Day 1 through Day 7 after the study vaccination. Events reported as adverse events in the case report form within 7 days after the study vaccination were also included in the analysis; the severity of these events is based on the grading scale in the adverse event section of the case report form. | |
| |
| Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) 3 mcg modRNA N * =36 n † (%) | |
| Fever | |
| ≥38.0℃ | 0 |
| Fatigue ‡ | |
| Any | 11 (30.6) |
| Mild | 6 (16.7) |
| Moderate | 5 (13.9) |
| Headache ‡ | |
| Any | 1 (2.8) |
| Mild | 1 (2.8) |
| Chills ‡ | |
| Any | 1 (2.8) |
| Mild | 1 (2.8) |
| Vomiting § | |
| Any | 1 (2.8) |
| Mild | 1 (2.8) |
| Diarrhea ¶ | |
| Any | 2 (5.6) |
| Mild | 1 (2.8) |
| Moderate | 1 (2.8) |
| New or worsened muscle pain ‡ | |
| Any | 0 |
| New or worsened joint pain ‡ | |
| Any | 1 (2.8) |
| Mild | 1 (2.8) |
| Use of antipyretic or pain medication # | 1 (2.8) |
Unsolicited Adverse Events
Participants 2 through 4 years of age who received a booster (fourth dose) with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.9 months (range 1.6 to 2.3 months) to the cutoff date (November 25, 2022).
Serious Adverse Events
No serious adverse events were reported in the 36 participants 2 through 4 years of age from the study vaccination through 1 month post vaccination.
Participants 6 Through 23 Months of Age Who Received a Booster Dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5)
In a subset of Study 6, 24 participants 6 through 23 months previously vaccinated with a 3-dose primary series of Pfizer-BioNTech COVID-19 Vaccine (3 mcg modRNA) received a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) (3 mcg modRNA).
Participants received a booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent 2.1 to 8.6 months after receiving their third dose with Pfizer-BioNTech COVID-19 and had a median follow-up time of 1.6 months (range 1.5 to 2.3 months) up to a data cutoff date of November 25, 2022. Their median age was 19 months (range 12 through 23 months), 58.3% were female and 41.7% were male, 54.2% were White, 20.8% were Asian, 20.8% were multi-racial, 16.7% were Hispanic/Latino, and 4.2% were Black or African American.
Solicited Local and Systemic Adverse Reactions
Table 19 and Table 20 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a booster (fourth dose) of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
The duration of injection site tenderness, swelling and redness for all events observed was 1 day.
Table 19: Local Adverse Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 6 Through 23 Months of Age – Safety Population
| Reactions were collected in the electronic diary (e-diary) and at unscheduled clinical assessments from Day 1 through Day 7 after the study vaccination. Reactions reported as adverse events in the case report form within 7 days after the study vaccination were also included in the analysis; the severity of these events is based on the grading scale in the adverse event section of the case report form. | |
| |
| Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) 3 mcg modRNA n ‡ (%) | |
| Redness § | |
| Any (≥0.5 cm) | 2 (8.3) |
| Mild | 2 (8.3) |
| Swelling § | |
| Any (≥0.5 cm) | 1 (4.2) |
| Mild | 1 (4.2) |
| Tenderness at the injection site ¶ | |
| Any | 1 (4.3) |
| Mild | 1 (4.3) |
Table 20: Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After a Booster (Fourth Dose) – Participants 6 Through 23 Months of Age – Safety Population
| Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) and at unscheduled clinical assessments from Day 1 through Day 7 after the study vaccination. Events reported as adverse events in the case report form within 7 days after the study vaccination were also included in the analysis; the severity of these events is based on the grading scale in the adverse event section of the case report form. | |
| |
| Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) 3 mcg modRNA n ‡ (%) | |
| Fever § | |
| ≥38.0℃ | 1 (4.2) |
| ≥38.0℃ to 38.4℃ | 1 (4.2) |
| Decreased appetite ¶ | |
| Any | 1 (4.5) |
| Mild | 1 (4.5) |
| Drowsiness # | |
| Any | 2 (9.1) |
| Mild | 2 (9.1) |
| Irritability Þ | |
| Any | 4 (18.2) |
| Mild | 3 (13.6) |
| Moderate | 1 (4.5) |
| Use of antipyretic or pain medication ß | 2 (8.3) |
Unsolicited Adverse Events
Participants 6 through 23 months of age who received a booster (fourth dose) with the Pfizer-BioNTech COVID-19 Vaccine, Bivalent had a median follow-up time of 1.6 months (range 1.5 to 2.3 months) to the cutoff date (November 25, 2022). In an analysis of all unsolicited adverse events reported following the booster dose through 1 month after the booster dose, the adverse reaction not already captured by solicited local and systemic reactions was injection site pain (n=1; 4.2%).
Serious Adverse Events
No serious adverse events were reported in the 24 participants 6 through 23 months of age from the study vaccination through 1 month post vaccination.
Non-Serious Adverse Events
Non-serious adverse events in participants 6 through 23 months of age from the study vaccination through 1 month post vaccination were reported in 3 (12.5%) Pfizer-BioNTech COVID-19 Vaccine, Bivalent recipients. Non-serious adverse events considered related to vaccination by the study investigator were fatigue (n=1; 4.2%) and injection site pain (n=1; 4.2%).
Bivalent Vaccine (Original and Omicron BA.1)
Bivalent Vaccine (Original and Omicron BA.1) Administered as a Second Booster Dose
In Study 4, a total of 610 participants greater than 55 years of age previously vaccinated with a 2-dose primary series and 1 booster dose of Pfizer-BioNTech COVID-19 Vaccine went on to receive a second booster dose with either Pfizer-BioNTech COVID-19 Vaccine or the bivalent vaccine (Original and Omicron BA.1).
The 305 participants greater than 55 years who received a second booster dose with Pfizer-BioNTech COVID-19 received it 5.3 to 13.1 months after receiving the first booster dose and had a median follow-up time of 1.8 months up to a data cutoff date of May 16, 2022. Their median age was 66 years (range 56 through 87 years of age), 47.5% were male and 52.5% were female, 87.9% were White, 18.7% were Hispanic/Latino, 4.3% were Asian, and 6.2% were Black or African American.
The 305 participants greater than 55 years who received a second booster dose with the bivalent vaccine (Original and Omicron BA.1) received it 4.7 to 11.5 months after receiving the first booster dose and had a median follow-up time of 1.7 months up to a data cutoff date of May 16, 2022. Their median age was 67 years (range 56 through 85 years of age), 53.1% were male and 46.9% were female, 89.8% were White, 14.8% were Hispanic/Latino, 5.2% were Asian, and 4.3% were Black or African American.
Solicited Local and Systemic Adverse Reactions
Local and systemic adverse reactions and use of antipyretic medication were solicited in an electronic diary for 7 days following each injection (i.e., day of vaccination and the next 6 days) among participants receiving bivalent vaccine (Original and Omicron BA.1) and participants receiving Pfizer-BioNTech COVID-19 Vaccine. Events that persisted for more than 7 days were followed until resolution.
Table 21 and Table 22 present the frequency and severity of reported solicited local and systemic adverse reactions within 7 days following a second booster dose with Pfizer-BioNTech, Bivalent vaccine (Original and Omicron BA.1) booster dose compared to Pfizer-BioNTech COVID-19 Vaccine in participants greater than 55 years of age.
In participants who received the bivalent vaccine (Original and Omicron BA.1), the mean duration of injection site pain, redness, and swelling was 2.2 days (range 1 to 12 days), 2.9 days (range 1 to 10 days), and 1.9 days (range 1 to 4 days), respectively.
| Pfizer-BioNTech COVID-19 Vaccine N * =298 n † (%) | Bivalent Vaccine (Original and Omicron BA.1) N * =301 n † (%) | |
|---|---|---|
| Note: Adverse Reactions were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination. | ||
| ||
| Redness ‡ | ||
| Any (>2 cm) | 19 (6.4) | 21 (7.0) |
| Mild | 12 (4.0) | 13 (4.3) |
| Moderate | 6 (2.0) | 8 (2.7) |
| Severe | 1 (0.3) | 0 |
| Swelling ‡ | ||
| Any (>2 cm) | 18 (6.0) | 20 (6.6) |
| Mild | 10 (3.4) | 14 (4.7) |
| Moderate | 8 (2.7) | 6 (2.0) |
| Severe | 0 | 0 |
| Pain at the injection site § | ||
| Any | 179 (60.1) | 175 (58.1) |
| Mild | 154 (51.7) | 159 (52.8) |
| Moderate | 24 (8.1) | 15 (5.0) |
| Severe | 1 (0.3) | 1 (0.3) |
| Pfizer-BioNTech COVID-19 Vaccine N * =298 n † (%) | Bivalent Vaccine (Original and Omicron BA.1) N * =301 n † (%) | |
|---|---|---|
| Note: Adverse reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination. | ||
| ||
| Fever | ||
| ≥38.0°C | 11 (3.7) | 15 (5.0) |
| ≥38.0°C to 38.4°C | 6 (2.0) | 11 (3.7) |
| >38.4°C to 38.9°C | 5 (1.7) | 0 |
| >38.9°C to 40.0°C | 0 | 4 (1.3) |
| >40.0°C | 0 | 0 |
| Fatigue ‡ | ||
| Any | 135 (45.3) | 148 (49.2) |
| Mild | 70 (23.5) | 88 (29.2) |
| Moderate | 64 (21.5) | 55 (18.3) |
| Severe | 1 (0.3) | 5 (1.7) |
| Headache ‡ | ||
| Any | 79 (26.5) | 101 (33.6) |
| Mild | 47 (15.8) | 71 (23.6) |
| Moderate | 31 (10.4) | 29 (9.6) |
| Severe | 1 (0.3) | 1 (0.3) |
| Chills ‡ | ||
| Any | 49 (16.4) | 39 (13.0) |
| Mild | 32 (10.7) | 25 (8.3) |
| Moderate | 17 (5.7) | 14 (4.7) |
| Severe | 0 | 0 |
| Vomiting § | ||
| Any | 4 (1.3) | 5 (1.7) |
| Mild | 2 (0.7) | 5 (1.7) |
| Moderate | 2 (0.7) | 0 |
| Severe | 0 | 0 |
| Diarrhea ¶ | ||
| Any | 13 (4.4) | 27 (9.0) |
| Mild | 10 (3.4) | 18 (6.0) |
| Moderate | 3 (1.0) | 5 (1.7) |
| Severe | 0 | 4 (1.3) |
| New or worsened muscle pain ‡ | ||
| Any | 59 (19.8) | 67 (22.3) |
| Mild | 35 (11.7) | 40 (13.3) |
| Moderate | 24 (8.1) | 27 (9.0) |
| Severe | 0 | 0 |
| New or worsened joint pain ‡ | ||
| Any | 27 (9.1) | 34 (11.3) |
| Mild | 16 (5.4) | 23 (7.6) |
| Moderate | 11 (3.7) | 11 (3.7) |
| Severe | 0 | 0 |
| Use of antipyretic or pain medication # | 80 (26.8) | 88 (29.2) |
Unsolicited Adverse Events
Overall, the participants who received a second booster dose with the bivalent vaccine (Original and Omicron BA.1) had a median follow-up time of 1.7 months (range 1.0 to 2.0 months) to the cutoff date (May 16, 2022).
In an analysis of all unsolicited adverse events reported following the second booster dose, through 1 month after the booster dose, those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (n=1, 0.3%) for the Pfizer-BioNTech COVID-19 Vaccine and (n=1, 0.3%) for the bivalent vaccine (Original and Omicron BA.1), nausea (n=1, 0.3%) for the Pfizer-BioNTech COVID-19 Vaccine and (n=1, 0.3%) for the bivalent vaccine (Original and Omicron BA.1), and malaise (n=0) for the Pfizer-BioNTech COVID-19 Vaccine and (n=1, 0.3%) for the bivalent vaccine (Original and Omicron BA.1).
Serious Adverse Events
Serious adverse events up to 1 month after the second booster dose in ongoing follow-up were reported by no Pfizer-BioNTech COVID-19 Vaccine recipients and by 1 bivalent vaccine (Original and Omicron BA.1) recipient (1 serious adverse event considered unrelated to the vaccine).
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