Vaccine Information: Comirnaty

COMIRNATY- tozinameran injection, suspension
Pfizer Laboratories Div Pfizer Inc

1 INDICATIONS AND USAGE

COMIRNATY is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 16 years of age and older.

2 DOSAGE AND ADMINISTRATION

For intramuscular injection only.

2.1 Preparation for Administration

The storage, preparation, and administration information in this Prescribing Information apply to COMIRNATY for individuals 16 years of age and older supplied in multiple dose vials with gray caps and labels with gray borders, which MUST NOT be diluted prior to use.

COMIRNATY Multiple Dose Vial with Gray Cap and Label with a Gray Border

Age Range	Dilution Information	Doses Per Vial	Dose Volume
16 years and older	Do not dilute prior to use	6	0.3 mL

DO NOT DILUTE

• COMIRNATY multiple dose vial with a gray cap and a label with a gray border contains a volume of 2.25 mL, supplied as a frozen suspension that does not contain preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
• Vials may be thawed in the refrigerator [2°C to 8°C (35°F to 46°F)] or at room temperature [up to 25°C (77°F)] [see How Supplied/Storage and Handling (16)].
• Refer to thawing instructions in the panels below.
• One vial contains 6 doses of 0.3 mL.

Preparation Instructions
COMIRNATY Vial with Gray Cap and Label with Gray Border – Vial Verification
	Verify that the vial of COMIRNATY has a gray plastic cap and a label with a gray border.
✔ Gray plastic cap and label with gray border.
COMIRNATY Vial with Gray Cap and Label with Gray Border – Thawing Prior to Use
(click image for full-size original)	Thaw vial(s) of COMIRNATY before use either by: Allowing vial(s) to thaw in the refrigerator [2°C to 8°C (35°F to 46°F)]. A carton of 10 vials may take up to 6 hours to thaw, and thawed vials can be stored in the refrigerator for up to 10 weeks. Allowing vial(s) to sit at room temperature [up to 25°C (77°F)] for 30 minutes. Vials may be stored at room temperature [up to 25°C (77°F)] for up to 12 hours prior to use.
(click image for full-size original)	Before use, mix by inverting vaccine vial gently 10 times. Do not shake. Prior to mixing, the thawed vaccine may contain white to off-white opaque amorphous particles. After mixing, the vaccine should appear as a white to off-white suspension with no visible particles. Do not use if liquid is discolored or if particles are observed after mixing.
Gently × 10
COMIRNATY Vial with Gray Cap and Label with Gray Border – Preparation of Individual 0.3 mL Doses
(click image for full-size original)	Withdraw 0.3 mL of COMIRNATY preferentially using low dead-volume syringes and/or needles. Each dose must contain 0.3 mL of vaccine. If the amount of vaccine remaining in a single vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume. Administer immediately.
Withdraw 0.3 mL dose of vaccine.
	Record the date and time of first vial puncture on the COMIRNATY vial label. Store between 2°C to 25°C (35°F to 77°F). Discard any unused vaccine 12 hours after first puncture.
Record the date and time of first puncture. Use within 12 hours after first puncture.

Vials of COMIRNATY with gray caps and labels with gray borders contain 6 doses of 0.3 mL of vaccine. Low dead-volume syringes and/or needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract 6 doses from a single vial. Irrespective of the type of syringe and needle,

• each dose must contain 0.3 mL of vaccine.
• if the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and any excess volume.
• do not pool excess vaccine from multiple vials.

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2.2 Administration Information

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The vaccine will be a white to off-white suspension. Do not administer if vaccine is discolored or contains particulate matter.

Administer a single 0.3 mL dose of COMIRNATY intramuscularly.

2.3 Vaccination Schedule

COMIRNATY is administered intramuscularly as a series of 2 doses (0.3 mL each) 3 weeks apart.

There are no data available on the interchangeability of COMIRNATY with COVID-19 vaccines from other manufacturers to complete the vaccination series. Individuals who have received 1 dose of COMIRNATY should receive a second dose of COMIRNATY to complete the vaccination series.

3 DOSAGE FORMS AND STRENGTHS

COMIRNATY is a suspension for injection. Each dose of COMIRNATY supplied in vials with gray caps and labels with gray borders is 0.3 mL.

4 CONTRAINDICATIONS

Do not administer COMIRNATY to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the COMIRNATY [see Description (11)].

5 WARNINGS AND PRECAUTIONS

5.1 Management of Acute Allergic Reactions

Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of COMIRNATY.

5.2 Myocarditis and Pericarditis

Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 12 through 17 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae. The CDC has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html).

5.3 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY. Procedures should be in place to avoid injury from fainting.

5.4 Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the COMIRNATY.

5.5 Limitation of Effectiveness

COMIRNATY may not protect all vaccine recipients.

6 ADVERSE REACTIONS

In clinical studies, the most commonly reported (≥10%) adverse reactions in participants 16 through 55 years of age following any dose were pain at the injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain (45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), and injection site swelling (10.6%).

In clinical studies, the most commonly reported (≥10%) adverse reactions in participants 56 years of age and older following any dose were pain at the injection site (78.2%), fatigue (56.9%), headache, (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection site swelling (11.8%), fever (11.5%), and injection site redness (10.4%).

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 to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.

The safety of COMIRNATY was evaluated in participants 16 years of age and older in 2 clinical studies conducted in Germany (Study 1), United States, Argentina, Brazil, Turkey, South Africa, and Germany (Study 2). 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 and 36 participants, 56 through 85 years of age. Study C4591001 (Study 2) is a Phase 1/2/3 multicenter, multinational, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study that has enrolled approximately 44,047 participants (22,026 COMIRNATY; 22,021 placebo) 16 years of age or older (including 378 and 376 participants 16 through 17 years of age in the vaccine and placebo groups, respectively). Upon issuance of the Emergency Use Authorization (December 11, 2020) for COMIRNATY, participants were unblinded to offer placebo participants COMIRNATY. Participants were unblinded in a phased manner over a period of months to offer placebo participants COMIRNATY. Study 2 also included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection; HIV-positive participants are included in safety population disposition but are summarized separately in safety analyses. Confirmed stable HIV infection was defined as documented viral load <50 copies/mL and CD4 count >200 cells/mm³ within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 months.

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

Participants 16 years and older in the reactogenicity subset 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 (all unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination].

Demographic characteristics in Study 2 were generally similar with regard to age, gender, 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 Adverse Reactions Solicited in the Study 2

Table 1 and Table 2 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo in the subset of participants 16 through 55 years of age included in the safety population who were monitored for reactogenicity with an electronic diary.

Table 3 and Table 4 present the frequency and severity of reported solicited local and systemic reactions, respectively, within 7 days of each dose of COMIRNATY and placebo for participants 56 years of age and older.

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.

Table 1: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of Age – Reactogenicity Subset of the Safety Population *

	COMIRNATY Dose 1 N †=2899 n ‡ (%)	Placebo Dose 1 N †=2908 n ‡ (%)	COMIRNATY Dose 2 N †=2682 n ‡ (%)	Placebo Dose 2 N †=2684 n ‡ (%)
Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. No Grade 4 solicited local reactions were reported in participants 16 through 55 years of age.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction was the same, therefore, this information was included in the column header. ‡ n = Number of participants with the specified reaction. § Mild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. ¶ Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Redness §
Any (>2.0 cm)	156 (5.4)	28 (1.0)	151 (5.6)	18 (0.7)
Mild	113 (3.9)	19 (0.7)	90 (3.4)	12 (0.4)
Moderate	36 (1.2)	6 (0.2)	50 (1.9)	6 (0.2)
Severe	7 (0.2)	3 (0.1)	11 (0.4)	0
Swelling §
Any (>2.0 cm)	184 (6.3)	16 (0.6)	183 (6.8)	5 (0.2)
Mild	124 (4.3)	6 (0.2)	110 (4.1)	3 (0.1)
Moderate	54 (1.9)	8 (0.3)	66 (2.5)	2 (0.1)
Severe	6 (0.2)	2 (0.1)	7 (0.3)	0
Pain at the injection site ¶
Any	2426 (83.7)	414 (14.2)	2101 (78.3)	312 (11.6)
Mild	1464 (50.5)	391 (13.4)	1274 (47.5)	284 (10.6)
Moderate	923 (31.8)	20 (0.7)	788 (29.4)	28 (1.0)
Severe	39 (1.3)	3 (0.1)	39 (1.5)	0

Table 2: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of Age – Reactogenicity Subset of the Safety Population *

	COMIRNATY Dose 1 N †=2899 n ‡ (%)	Placebo Dose 1 N †=2908 n ‡ (%)	COMIRNATY Dose 2 N †=2682 n ‡ (%)	Placebo Dose 2 N †=2684 n ‡ (%)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. No Grade 4 solicited systemic reactions were reported in participants 16 through 55 years of age.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction or use of antipyretic or pain medication was the same, therefore, this information was included in the column header. ‡ n = Number of participants with the specified reaction. § Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. ¶ Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. # Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours. Þ Severity was not collected for use of antipyretic or pain medication.
Fever
≥38.0°C	119 (4.1)	25 (0.9)	440 (16.4)	11 (0.4)
≥38.0°C to 38.4°C	86 (3.0)	16 (0.6)	254 (9.5)	5 (0.2)
>38.4°C to 38.9°C	25 (0.9)	5 (0.2)	146 (5.4)	4 (0.1)
>38.9°C to 40.0°C	8 (0.3)	4 (0.1)	39 (1.5)	2 (0.1)
>40.0°C	0	0	1 (0.0)	0
Fatigue §
Any	1431 (49.4)	960 (33.0)	1649 (61.5)	614 (22.9)
Mild	760 (26.2)	570 (19.6)	558 (20.8)	317 (11.8)
Moderate	630 (21.7)	372 (12.8)	949 (35.4)	283 (10.5)
Severe	41 (1.4)	18 (0.6)	142 (5.3)	14 (0.5)
Headache §
Any	1262 (43.5)	975 (33.5)	1448 (54.0)	652 (24.3)
Mild	785 (27.1)	633 (21.8)	699 (26.1)	404 (15.1)
Moderate	444 (15.3)	318 (10.9)	658 (24.5)	230 (8.6)
Severe	33 (1.1)	24 (0.8)	91 (3.4)	18 (0.7)
Chills §
Any	479 (16.5)	199 (6.8)	1015 (37.8)	114 (4.2)
Mild	338 (11.7)	148 (5.1)	477 (17.8)	89 (3.3)
Moderate	126 (4.3)	49 (1.7)	469 (17.5)	23 (0.9)
Severe	15 (0.5)	2 (0.1)	69 (2.6)	2 (0.1)
Vomiting ¶
Any	34 (1.2)	36 (1.2)	58 (2.2)	30 (1.1)
Mild	29 (1.0)	30 (1.0)	42 (1.6)	20 (0.7)
Moderate	5 (0.2)	5 (0.2)	12 (0.4)	10 (0.4)
Severe	0	1 (0.0)	4 (0.1)	0
Diarrhea #
Any	309 (10.7)	323 (11.1)	269 (10.0)	205 (7.6)
Mild	251 (8.7)	264 (9.1)	219 (8.2)	169 (6.3)
Moderate	55 (1.9)	58 (2.0)	44 (1.6)	35 (1.3)
Severe	3 (0.1)	1 (0.0)	6 (0.2)	1 (0.0)
New or worsened muscle pain §
Any	664 (22.9)	329 (11.3)	1055 (39.3)	237 (8.8)
Mild	353 (12.2)	231 (7.9)	441 (16.4)	150 (5.6)
Moderate	296 (10.2)	96 (3.3)	552 (20.6)	84 (3.1)
Severe	15 (0.5)	2 (0.1)	62 (2.3)	3 (0.1)
New or worsened joint pain §
Any	342 (11.8)	168 (5.8)	638 (23.8)	147 (5.5)
Mild	200 (6.9)	112 (3.9)	291 (10.9)	82 (3.1)
Moderate	137 (4.7)	55 (1.9)	320 (11.9)	61 (2.3)
Severe	5 (0.2)	1 (0.0)	27 (1.0)	4 (0.1)
Use of antipyretic or pain medication Þ	805 (27.8)	398 (13.7)	1213 (45.2)	320 (11.9)

Table 3: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety Population *

	COMIRNATY Dose 1 N †=2008 n ‡ (%)	Placebo Dose 1 N †=1989 n ‡ (%)	COMIRNATY Dose 2 N †=1860 n ‡ (%)	Placebo Dose 2 N †=1833 n ‡ (%)
Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. No Grade 4 solicited local reactions were reported in participants 56 years of age and older.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction was the same, therefore, the information was included in the column header. ‡ n = Number of participants with the specified reaction. § Mild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. ¶ Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Redness §
Any (>2.0 cm)	106 (5.3)	20 (1.0)	133 (7.2)	14 (0.8)
Mild	71 (3.5)	13 (0.7)	65 (3.5)	10 (0.5)
Moderate	30 (1.5)	5 (0.3)	58 (3.1)	3 (0.2)
Severe	5 (0.2)	2 (0.1)	10 (0.5)	1 (0.1)
Swelling §
Any (>2.0 cm)	141 (7.0)	23 (1.2)	145 (7.8)	13 (0.7)
Mild	87 (4.3)	11 (0.6)	80 (4.3)	5 (0.3)
Moderate	52 (2.6)	12 (0.6)	61 (3.3)	7 (0.4)
Severe	2 (0.1)	0	4 (0.2)	1 (0.1)
Pain at the injection site ¶
Any (>2.0 cm)	1408 (70.1)	185 (9.3)	1230 (66.1)	143 (7.8)
Mild	1108 (55.2)	177 (8.9)	873 (46.9)	138 (7.5)
Moderate	296 (14.7)	8 (0.4)	347 (18.7)	5 (0.3)
Severe	4 (0.2)	0	10 (0.5)	0

Table 4: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety Population *

	COMIRNATY Dose 1 N †=2008 n ‡ (%)	Placebo Dose 1 N †=1989 n ‡ (%)	COMIRNATY Dose 2 N †=1860 n ‡ (%)	Placebo Dose 2 N †=1833 n ‡ (%)
Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. The only Grade 4 solicited systemic reaction reported in participants 56 years of age and older was fatigue.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. N for each reaction or use of antipyretic or pain medication was the same, therefore was included in the column header. ‡ n = Number of participants with the specified reaction. § Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity; Grade 4 reactions were defined in the clinical study protocol as emergency room visit or hospitalization for severe fatigue, severe headache, severe chills, severe muscle pain, or severe joint pain. ¶ Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration; Grade 4 emergency visit or hospitalization for severe vomiting. # Mild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours; Grade 4: emergency room or hospitalization for severe diarrhea. Þ Severity was not collected for use of antipyretic or pain medication.
Fever
≥38.0°C	26 (1.3)	8 (0.4)	219 (11.8)	4 (0.2)
≥38.0°C to 38.4°C	23 (1.1)	3 (0.2)	158 (8.5)	2 (0.1)
>38.4°C to 38.9°C	2 (0.1)	3 (0.2)	54 (2.9)	1 (0.1)
>38.9°C to 40.0°C	1 (0.0)	2 (0.1)	7 (0.4)	1 (0.1)
>40.0°C	0	0	0	0
Fatigue §
Any	677 (33.7)	447 (22.5)	949 (51.0)	306 (16.7)
Mild	415 (20.7)	281 (14.1)	391 (21.0)	183 (10.0)
Moderate	259 (12.9)	163 (8.2)	497 (26.7)	121 (6.6)
Severe	3 (0.1)	3 (0.2)	60 (3.2)	2 (0.1)
Grade 4	0	0	1 (0.1)	0
Headache §
Any	503 (25.0)	363 (18.3)	733 (39.4)	259 (14.1)
Mild	381 (19.0)	267 (13.4)	464 (24.9)	189 (10.3)
Moderate	120 (6.0)	93 (4.7)	256 (13.8)	65 (3.5)
Severe	2 (0.1)	3 (0.2)	13 (0.7)	5 (0.3)
Chills §
Any	130 (6.5)	69 (3.5)	435 (23.4)	57 (3.1)
Mild	102 (5.1)	49 (2.5)	229 (12.3)	45 (2.5)
Moderate	28 (1.4)	19 (1.0)	185 (9.9)	12 (0.7)
Severe	0	1 (0.1)	21 (1.1)	0
Vomiting ¶
Any	10 (0.5)	9 (0.5)	13 (0.7)	5 (0.3)
Mild	9 (0.4)	9 (0.5)	10 (0.5)	5 (0.3)
Moderate	1 (0.0)	0	1 (0.1)	0
Severe	0	0	2 (0.1)	0
Diarrhea #
Any	168 (8.4)	130 (6.5)	152 (8.2)	102 (5.6)
Mild	137 (6.8)	109 (5.5)	125 (6.7)	76 (4.1)
Moderate	27 (1.3)	20 (1.0)	25 (1.3)	22 (1.2)
Severe	4 (0.2)	1 (0.1)	2 (0.1)	4 (0.2)
New or worsened muscle pain §
Any	274 (13.6)	165 (8.3)	537 (28.9)	99 (5.4)
Mild	183 (9.1)	111 (5.6)	229 (12.3)	65 (3.5)
Moderate	90 (4.5)	51 (2.6)	288 (15.5)	33 (1.8)
Severe	1 (0.0)	3 (0.2)	20 (1.1)	1 (0.1)
New or worsened joint pain §
Any	175 (8.7)	124 (6.2)	353 (19.0)	72 (3.9)
Mild	119 (5.9)	78 (3.9)	183 (9.8)	44 (2.4)
Moderate	53 (2.6)	45 (2.3)	161 (8.7)	27 (1.5)
Severe	3 (0.1)	1 (0.1)	9 (0.5)	1 (0.1)
Use of antipyretic or pain medication Þ	382 (19.0)	224 (11.3)	688 (37.0)	170 (9.3)

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 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 3 and Table 4).

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.

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 (COMIRNATY =12,995; placebo = 13,026), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (COMIRNATY = 8,931; placebo = 8,895), serious adverse events were reported by 165 (1.8%) COMIRNATY recipients and 151 (1.7%) placebo recipients who received at least 1 dose of COMIRNATY or placebo, respectively. In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants with confirmed stable HIV infection serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 2 (2%) COMIRNATY recipients and 2 (2%) placebo recipients.

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.