At the time of the analysis of Study 2 with a data cutoff of March 13, 2021, there were 25,651 (58.2%) participants (13,031 COMIRNATY; 12,620 placebo) 16 years of age and older followed for ≥4 months after the second dose.

Demographic characteristics in Study 2 were generally similar with regard to age, sex, race, and ethnicity among participants who received COMIRNATY and those who received placebo. Overall, among the total participants who received either COMIRNATY or placebo, 50.9% were male, 49.1% were female, 79.3% were 16 through 64 years of age, 20.7% were 65 years of age and older, 82.0% were White, 9.6% were Black or African American, 25.9% were Hispanic/Latino, 4.3% were Asian, and 1.0% were American Indian or Alaska Native.

Local and Systemic Solicited Adverse Reactions

In participants 16 through 55 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 70 days), for redness 2.2 days (range 1 to 9 days), and for swelling 2.1 days (range 1 to 8 days) for participants in the COMIRNATY group.

In participants 56 years of age and older after receiving Dose 2, the mean duration of pain at the injection site was 2.4 days (range 1 to 36 days), for redness 3.0 days (range 1 to 34 days), and for swelling 2.6 days (range 1 to 34 days) for participants in the COMIRNATY group.

In participants with chronic, stable HIV infection the frequencies of solicited local and systemic adverse reactions were similar to or lower than those observed for all participants 16 years of age and older.

Unsolicited Adverse Events

Overall, 11,253 (51.1%) participants 16 years of age and older in the COMIRNATY group and 11,316 (51.4%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 1,778 (8.1%) and 1,304 (5.9%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.

A total of 12,006 (54.5%) participants originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2.

In an analysis of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in participants 16 years of age and older (N = 43,847; 21,926 COMIRNATY group vs. 21,921 placebo group), those assessed as adverse reactions not already captured by solicited local and systemic reactions were nausea (274 vs. 87), malaise (130 vs. 22), lymphadenopathy (83 vs. 7), asthenia (76 vs. 25), decreased appetite (39 vs. 9), hyperhidrosis (31 vs. 9), lethargy (25 vs. 6), and night sweats (17 vs. 3).

In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants 16 through 55 years of age who received at least 1 dose of study vaccine, 12,995 of whom received COMIRNATY and 13,026 of whom received placebo, unsolicited adverse events were reported by 4,396 (33.8%) participants in the COMIRNATY group and 2,136 (16.4%) participants in the placebo group. In a similar analysis in participants 56 years of age and older that included 8,931 COMIRNATY recipients and 8,895 placebo recipients, unsolicited adverse events were reported by 2,551 (28.6%) participants in the COMIRNATY group and 1,432 (16.1%) participants in the placebo group. Among participants with confirmed stable HIV infection that included 100 COMIRNATY recipients and 100 placebo recipients, unsolicited adverse events were reported by 29 (29%) participants in the COMIRNATY group and 15 (15%) participants in the placebo group. The higher frequency of reported unsolicited adverse events among COMIRNATY recipients compared to placebo recipients was primarily attributed to events that are consistent with adverse reactions solicited among participants in the reactogenicity subset (Table 5 and Table 6).

Throughout the placebo-controlled safety follow-up period, Bell’s palsy (facial paralysis) was reported by 4 participants in the COMIRNATY group and 2 participants in the placebo 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. In the placebo group the onset of facial paralysis was Day 32 and Day 102. Currently available information is insufficient to determine a causal relationship with the vaccine. In the analysis of blinded, placebo-controlled follow-up, 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 COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.

Two-Dose Series (Original Monovalent) in Vaccine-Naïve Adolescents 12 Through 15 Years of Age

Study 2 was a Phase 1/2/3 multicenter, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study. In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. At the time of the analysis of the ongoing Study 2 with a data cutoff of September 2, 2021, there were 1,559 (69.0%) adolescents (786 COMIRNATY and 773 placebo) 12 through 15 years of age followed for ≥4 months after the second dose.

Demographic characteristics in Study 2 were generally similar with regard to age, sex, race, and ethnicity among adolescents who received COMIRNATY and those who received placebo. Overall, among the adolescents who received COMIRNATY, 50.1% were male and 49.9% were female, 85.8% 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.

In Study 2, participants 12 through 15 years of age in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Tables 7 through 8 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.

Local and Systemic Solicited Adverse Reactions

In adolescents 12 through 15 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 11 days), for redness 1.8 days (range 1 to 5 days), and for swelling 1.6 days (range 1 to 5 days) in the COMIRNATY group.

Unsolicited Adverse Events

In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. Of these, 634 (56.1%) participants in the COMIRNATY group and 629 (55.7%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 152 (13.4%) and 144 (12.8%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.

A total of 1,113 (98.4%) participants 12 through 15 years of age originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2. An analysis of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date was conducted. Among participants 12 through 15 years of age who received at least 1 dose of study vaccine, unsolicited adverse events were reported by 95 (8.4%) participants in the COMIRNATY group and 113 (10.0%) participants in the placebo group.

In an analysis of all unsolicited adverse events reported during blinded follow-up from Dose 1 through 1 month after Dose 2, in adolescents 12 to 15 years of age, those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (9 vs. 2), and nausea (5 vs. 2).

In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of unsolicited adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.

Serious Adverse Events

In Study 2, among participants 12 through 15 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY = 1,131; placebo = 1,129), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 10 (0.9%) COMIRNATY recipients and 2 (0.2%) placebo recipients. In these analyses, 69.0% of study participants had at least 4 months of follow-up after Dose 2. In the analysis of blinded, placebo-controlled follow-up, there were no notable patterns between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY.

Single Dose (Original Monovalent) in Vaccine-Experienced Individuals 12 Years of Age and Older

16 Years of Age and Older

In Study 4, a double-blind placebo-controlled booster study, 5,081 participants 16 years of age and older recruited from Study 2 received a booster dose of COMIRNATY 10.8 months (median time, range of 5.0 to 12.6 months) after completing the primary series of COMIRNATY series and had a median follow-up time of 2.9 months based on data up to the cutoff date of February 8, 2022. The median age of participants who received COMIRNATY or placebo was 53.0 years (range 16 through 87 years of age), 49.1% were male and 50.9% were female, 79.0% were White, 14.9% were Hispanic/Latino, 9.2% were Black or African American, 5.5% were Asian, and 1.7% were American Indian/Alaska Native.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 141 (2.8%) participants who received a booster dose of COMIRNATY and in 83 (0.4%) participants who received COMIRNATY as a primary series.

18 Years Through 55 Years of Age

A subset of 306 Study 2 Phase 2/3 participants 18 through 55 years of age received a booster dose of COMIRNATY 6.8 months (median time, range 4.8 to 8.0 months) after completing the primary series. These participants had a median follow-up time of 8.3 months up to a data cutoff date of November 22, 2021. Among the 306 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.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 16 (5.2%) of participants who received a booster dose of COMIRNATY and 83 (0.4%) in participants who received COMIRNATY as a primary series.

12 Years Through 17 Years of Age

A subset of 65 Study 4 participants 12 through 17 years of age received a booster dose of COMIRNATY 13.3 months (median time, range 6.5 to 16.9 months) after completing the primary series and had a median follow-up time of 5.6 months up to a data cutoff date of July 14, 2022. The median age of participants was 14 years (range 12 through 17 years of age), 49.2% were male and 50.8% were female, 76.9% were White, 16.9% were Hispanic/Latino, 13.8% were Black or African American, 7.7% were Asian, and 1.5% were American Indian/Alaska Native.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. There were no cases of lymphadenopathy reported in participants who received a booster dose of COMIRNATY.

12 Years Through 15 Years of Age

A subset of 825 Study 2 Phase 2/3 participants 12 through 15 years of age received a booster dose of COMIRNATY 11.2 months (median time, range 6.3 to 20.1 months) after completing the primary series and had a median follow-up time of 9.5 months up to a data cutoff date of November 3, 2022. The median age of participants was 14.0 years (range 13 through 15 years of age), 49.3% were male and 50.7% were female, 83.5% were White, 10.8% were Hispanic/Latino, 4.6% were Black or African American, 7.5% were Asian, and 0.4% were American Indian/Alaska Native.

Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 8 (1.0%) participants who received a booster dose of COMIRNATY and in 9 (0.8%) participants who received COMIRNATY as a primary series.

Single Dose (Bivalent Original and BA.4/BA.5) in Vaccine-Experienced Individuals 12 Years of Age and Older

A subset of 107 Study 5 Phase 2/3 participants 12 through 17 years of age, 313 participants 18 through 55 years of age and 306 participants 56 years of age and older previously vaccinated with a 2-dose primary series and 1 booster dose of COMIRNATY, went on to receive a second booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

Participants received a second booster dose 11.1 months (median time; range 5.4 to 16.9 months) after receiving the first booster dose and had a median follow-up time of 1.5 months up to a data cutoff date of October 31, 2022. The median age was 48.0 years, 42.7% were male, 57.3% were female, 80.6% were White, 11.4% were Hispanic/Latino, 5.9% were Asian, and 11.4% were Black or African American.

Local and Systemic Solicited Adverse Reactions

Table 9 and Table 10 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.

In participants 12 years of age and older who received a second booster dose, the mean duration of injection site pain was 2.1 to 2.4 days (range 1 to 11 days), injection site redness was 1.5 to 2.5 days (range 1 to 4 days), and injection site swelling was 1.3 to 1.9 days (range 1 to 4 days), respectively.

Unsolicited Adverse Events

Among participants 12 years of age and older, unsolicited adverse events were reported by 48 (6.6%) participants who received a second booster dose through 1 month after the booster dose. Lymphadenopathy occurred in 7 (1.0%) participants.

Concomitant Administration of COMIRNATY (Original Monovalent) With Influenza Vaccine in Adults 18 Years Through 64 Years of Age

In Study 8, a Phase 3 study, participants 18 through 64 years of age who received COMIRNATY concomitantly administered with Influenza Vaccine (Afluria Quadrivalent) followed 1 month later by saline placebo (n = 564) were compared to participants who received influenza vaccine with saline placebo followed 1 month later by COMIRNATY (n = 564).

Demographic characteristics in Study 8 among the participants in the concomitant administration and separate administration groups were similar with regard to age, sex, race, and ethnicity. Among the 564 participants in the concomitant administration group, the median age was 39.0 years (range 18 through 64 years of age), 36.9% were male and 63.1% were female, 79.1% were White, 12.9% were Asian, and 0.9% were Hispanic/Latino.

Solicited local and systemic adverse reactions were reported more frequently by participants who received COMIRNATY concomitantly with influenza vaccine, compared to participants who received COMIRNATY alone. The most common adverse reactions reported in the concomitant administration group and after COMIRNATY alone were injection site pain (COMIRNATY injection site) (86.2% and 84.4%, respectively), fatigue (64.0% and 50.8%, respectively), and headache (47.2% and 37.8%, respectively).

Children 5 Years Through 11 Years of Age

Two-Dose Series (Original Monovalent) in Vaccine-Naïve Children 5 Years Through 11 Years of Age

Study 3 is a Phase 1/2/3 multicenter, randomized, dose-finding, open label (Phase 1) and multinational, placebo controlled (saline placebo), observer-blind, immunogenicity and efficacy (Phase 2/3) study that has evaluated 4,695 participants 5 through 11 years of age, of whom 3,109 participants received COMIRNATY and 1,538 participants received placebo in Phase 2/3.

Demographic characteristics were generally similar with regard to age, sex, race, and ethnicity among participants who received COMIRNATY and those who received placebo. Overall, among the 4,647 participants who received at least 1 dose of COMIRNATY or placebo, 51.4% were male and 48.6% were female, 77.5% were White, 6.0% were Black or African American, 17.0% were Hispanic/Latino, 8.1% were Asian, and 0.4% were American Indian/Alaska Native.

In an analysis of Study 3 (Phase 2/3), 4,632 participants 5 through 11 years of age who received a 2-dose primary series [3,100 COMIRNATY; 1,532 placebo] have been followed a median of 1.9 months (range 0.1 to 7.5 months) after the second dose in the blinded placebo-controlled follow-up period up to the cutoff date of May 20, 2022.

In Study 3, participants 5 years through 11 years of age in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic adverse reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Tables 11 through 12 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.

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 37 days), for redness 2.0 days (range 1 to 10 days), and for swelling 2.2 days (range 1 to 16 days) for children in the COMIRNATY group in the blinded placebo-controlled follow-up period up to the cutoff date of May 20, 2022.

Unsolicited Adverse Events

In the following analyses of Study 3 in participants 5 through 11 years of age, 3,109 participants received COMIRNATY and 1,538 participants received placebo. Among those who received 2 doses of COMIRNATY or placebo, 1,185 participants in the COMIRNATY group and 575 participants in the placebo group had follow-up time ≥4 to <6 months and 296 participants in the COMIRNATY group and 150 participants in the placebo group had follow-up time of >6 months in the blinded placebo-controlled follow-up period.

Among participants who received at least 1 dose of study vaccine, unsolicited adverse events were reported by 333 (10.7%) participants in the COMIRNATY group and 150 (9.8%) participants in the placebo group.

In an analysis of all unsolicited adverse events reported following administration of Dose 1 to one month after administration of Dose 2, the adverse reactions (excluding reactions reported as solicited adverse reactions) in participants who received COMIRNATY compared with participants who received placebo were lymphadenopathy (n=23; 0.7% vs. n=4; 0.3%), nausea (n=7; 0.2% vs. n=3; 0.2%), decreased appetite (n=3; 0.1% vs. n=2; 0.1%), malaise (n=2; 0.1% vs. n=0), and night sweats (n=1; 0.0% vs. n=0).

Serious Adverse Events

Serious adverse events, from administration of Dose 1 to the participant unblinding date, were reported in 8 (0.3%) COMIRNATY recipients and in 2 (0.1%) placebo recipients. No serious adverse events were considered related to vaccination.

Single Dose (Original Monovalent) in Vaccine-Experienced Children 5 Years Through 11 Years of Age

In Phase 2/3 of Study 3, 2,408 participants 5 years through 11 years of age received a first booster dose of COMIRNATY at a median of 7.9 months (range 5.3 to 19.4 months) after completing the primary series. These participants had a median safety follow-up of 6.4 months from vaccination through the data cutoff date of February 28, 2023. The median age was 8.0 years (range 5 through 11 years of age), 50.5% were male and 49.5% were female, 76.3% were White, 5.9% were Black or African American, 16.9% were Hispanic/Latino, 8.2% were Asian, and 0.5% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

The frequency of solicited adverse reactions reported in participants receiving a booster dose of COMIRNATY were generally consistent with those reported in pediatric participants receiving COMIRNATY as part of the two-dose series.

Unsolicited Adverse Events

Lymphadenopathy occurred in 46 (1.9%) participants who received a booster dose of COMIRNATY and in 23 (0.7%) participants who received COMIRNATY as a primary series.

Serious Adverse Events

Serious adverse events from study vaccination through 6 months after study vaccination were reported by 10 (0.4%) COMIRNATY recipients. No serious adverse events were considered related to vaccination.

Single Dose (Bivalent Original and BA.4/BA.5) in Vaccine-Experienced Children 5 Years Through 11 Years of Age

In Study 6, 113 participants 5 years through 11 years of age previously vaccinated with a 2-dose primary series and 1 booster dose of COMIRNATY received a second booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5). Participants received a second booster with Pfizer-BioNTech COVID-19, Bivalent 2.6 to 8.5 months after receiving their third dose with COMIRNATY and had a median follow-up time of 6.3 months (range 1.1 to 6.8 months) up to a data cutoff date of April 20, 2023. The median age of participants 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 multiracial, 11.5% were Asian, and 8.0% were Black or African American.

Solicited Local and Systemic Adverse Reactions

The frequency of solicited adverse reactions reported in participants receiving a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and BA.4/BA.5) were generally consistent with those reported in pediatric participants receiving COMIRNATY.

Unsolicited Adverse Events

Lymphadenopathy was reported in 1 (0.9%) participant who received Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and BA.4/BA.5).

Serious Adverse Events

No serious adverse events were reported.

Single Dose (Monovalent XBB.1.5) in Vaccine-Naïve Children 5 Years Through 11 Years of Age

In a subset of Study 6, the safety of a single dose of COMIRNATY (encoding the viral spike (S) glycoprotein of SARS-CoV-2 Omicron XBB.1.5) was evaluated in 310 COVID-19 vaccine-naïve participants 5 through 11 years of age. Participants had a median follow-up time of 6.4 months (range 1.7 to 6.9 months). The median age of participants was 7.0 years (range 5 through 11 years of age), 47.1% were male and 52.9% were female, 41.3% were White, 52.9% were Black or African American, 52.3% were Hispanic or Latino, 1.9% were Asian, and 0.3% were American Indian/Alaska Native.

Solicited Local and Systemic Adverse Reactions

The frequency of solicited adverse reactions reported in participants who received a single dose of COMIRNATY, monovalent (XBB.1.5) were generally consistent with those previously reported by participants receiving COMIRNATY.

Unsolicited Adverse Events

In an analysis of all unsolicited adverse events through 1 month after study vaccination, unsolicited adverse events were reported by 11 (3.5%) COMIRNATY recipients. The adverse reaction not already captured by solicited local and systemic reactions was decreased appetite (n=1; 0.3%).

Serious Adverse Events

Serious adverse events from study vaccination through 6 months after study vaccination were reported by 3 (1.0%) COMIRNATY recipients. No serious adverse events were considered related to vaccination.