pfizer report page 67

PFIZER-BIONTECH COVID-19 VACCINE- bnt162b2 injection, suspension  Pfizer Manufacturing Belgium NV

PFIZER-BIONTECH COVID-19 VACCINE

FACT SHEET FOR HEALTHCARE PROVIDERS ADMINISTERING VACCINE (VACCINATION PROVIDERS)

EMERGENCY USE AUTHORIZATION (EUA) OF THE PFIZER-BIONTECH COVID-19 VACCINE TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19)

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved product, Pfizer-BioNTech COVID-19 Vaccine, for active immunization to prevent COVID-19 in individuals 6 months of age and older.

There are 2 formulations of Pfizer-BioNTech COVID-19 Vaccine authorized for use in individuals 12 years of age and older:

This Fact Sheet pertains only to Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a purple cap, which is authorized for use in individuals 12 years of age and older and MUST BE DILUTED PRIOR TO USE.

Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a purple cap is authorized for use to provide:

COMIRNATY (COVID-19 Vaccine, mRNA) is an FDA-approved COVID-19 vaccine made by Pfizer for BioNTech that is indicated for active immunization to prevent COVID-19 in individuals 12 years of age and older. It is approved for use as a 2-dose primary series for the prevention of COVID-19 in individuals 12 years of age and older. It is also authorized for emergency use to provide a third primary series dose to individuals 12 years of age and older with certain kinds of immunocompromise.

The FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the EUA-authorized Pfizer-BioNTech COVID-19 Vaccine for individuals 12 years of age and older when prepared according to their respective instructions for use can be used interchangeably. 2

COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine intended for individuals 12 years of age and older should not be used for individuals 6 months through 11 years of age because of the potential for vaccine administration errors, including dosing errors. 3

SUMMARY OF INSTRUCTIONS FOR COVID-19 VACCINATION PROVIDERS

Vaccination providers enrolled in the federal COVID-19 Vaccination Program must report all vaccine administration errors, all serious adverse events, cases of myocarditis, cases of pericarditis, cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and cases of COVID-19 that result in hospitalization or death following administration of Pfizer-BioNTech COVID-19 Vaccine. See " MANDATORY REQUIREMENTS FOR PFIZER-BIONTECH COVID-19 VACCINE ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION " for reporting requirements.

The Pfizer-BioNTech COVID-19 Vaccine is a suspension for intramuscular injection.

Primary Series

The Pfizer-BioNTech COVID-19 Vaccine is administered as a primary series of 2 doses (0.3 mL each) 3 weeks apart in individuals 12 years of age or older.

A third primary series dose of the Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) at least 28 days following the second dose is authorized for administration to individuals at least 12 years of age with certain kinds of immunocompromise.

See this Fact Sheet for instructions for preparation and administration. This Fact Sheet may have been updated. For the most recent Fact Sheet, please see www.cvdvaccine.com .

For information on clinical trials that are testing the use of the Pfizer-BioNTech COVID-19 Vaccine for active immunization to prevent COVID-19, please see www.clinicaltrials.gov .

DESCRIPTION OF COVID-19

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus, SARS-CoV-2, that appeared in late 2019. It is predominantly a respiratory illness that can affect other organs. People with COVID-19 have reported a wide range of symptoms, ranging from mild symptoms to severe illness. Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may include: fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhea.

DOSAGE AND ADMINISTRATION

The storage, preparation, and administration information in this Fact Sheet apply to the Pfizer-BioNTech COVID-19 Vaccine for individuals 12 years of age and older, which is supplied in a multiple dose vial with a purple cap and MUST BE DILUTED before use.

Storage and Handling

During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.

Do not refreeze thawed vials.

Frozen Vials Prior to Use

Cartons of Pfizer-BioNTech COVID-19 Vaccine multiple dose vials with purple caps arrive in thermal containers with dry ice. Once received, remove the vial cartons immediately from the thermal container and preferably store in an ultra-low temperature freezer between -90ºC to -60ºC (-130ºF to -76ºF) until the expiry date printed on the label. This information in the package insert supersedes the storage conditions printed on the vial cartons.

Cartons and vials of Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with purple caps with an expiry date of December 2021 through December 2022 printed on the label may remain in use beyond the printed date until the updated expiry date shown below; as long as approved storage conditions have been maintained.

If not stored between -90ºC to -60ºC (-130ºF to -76ºF), vials may be stored at -25°C to -15°C (-13°F to 5°F) for up to 2 weeks. Vials must be kept frozen and protected from light until ready to use. Vials stored at -25°C to -15°C (-13°F to 5°F) for up to 2 weeks may be returned one time to the recommended storage condition of -90ºC to -60ºC (-130ºF to -76ºF). Total cumulative time the vials are stored at -25°C to -15°C (-13°F to 5°F) should be tracked and should not exceed 2 weeks.

If an ultra-low temperature freezer is not available, the thermal container in which the Pfizer-BioNTech COVID-19 Vaccine arrives may be used as temporary storage when consistently re-filled to the top of the container with dry ice. Refer to the re-icing guidelines packed in the original thermal container for instructions regarding the use of the thermal container for temporary storage . The thermal container maintains a temperature range of -90ºC to -60ºC (-130ºF to -76ºF). Storage of the vials between -96°C to -60°C (-141°F to -76°F) is not considered an excursion from the recommended storage condition.

Transportation of Frozen Vials

If local redistribution is needed and full cartons containing vials cannot be transported at -90°C to -60°C (-130°F to -76°F), vials may be transported at -25°C to -15°C (-13°F to 5°F). Any hours used for transport at -25°C to -15°C (-13°F to 5°F) count against the 2-week limit for storage at -25°C to -15°C (-13°F to 5°F). Frozen vials transported at -25°C to -15°C (-13°F to 5°F) may be returned one time to the recommended storage condition of -90ºC to -60ºC (-130ºF to -76ºF).

Thawed Vials Before Dilution

Thawed Under Refrigeration

Thaw and then store undiluted vials in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] for up to 1 month. A carton of 25 vials or 195 vials may take up to 2 or 3 hours, respectively, to thaw in the refrigerator, whereas a fewer number of vials will thaw in less time.

Thawed at Room Temperature

For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for 30 minutes. Thawed vials can be handled in room light conditions. Vials must reach room temperature before dilution.

Undiluted vials may be stored at room temperature for no more than 2 hours.

Transportation of Thawed Vials

Available data support transportation of one or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 48 hours.

Vials After Dilution

Dosing and Schedule

The Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly as a primary series of 2 doses (0.3 mL each) 3 weeks apart to individuals 12 years of age and older.

Dose Preparation

Each vial MUST BE DILUTED before administering the vaccine.

Prior to Dilution

Dilute the vial contents using 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP (not provided) to form the Pfizer-BioNTech COVID-19 Vaccine. ONLY use sterile 0.9% Sodium Chloride Injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately. Do not use bacteriostatic 0.9% Sodium Chloride Injection or any other diluent . Do not add more than 1.8 mL of diluent.

After dilution, 1 vial contains 6 doses of 0.3 mL.

Administration

Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off-white suspension. During the visual inspection,

Administer the Pfizer-BioNTech COVID-19 Vaccine intramuscularly.

After dilution, vials of Pfizer-BioNTech COVID-19 Vaccine with purple caps 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:

Contraindications

Do not administer Pfizer-BioNTech COVID-19 Vaccine to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 Vaccine (see Full EUA Prescribing Information ) .

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 Pfizer-BioNTech COVID-19 Vaccine.

Monitor Pfizer-BioNTech COVID-19 Vaccine recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention (CDC) guidelines ( https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html ).

Myocarditis and Pericarditis

Postmarketing data with Pfizer-BioNTech COVID-19 Vaccine demonstrate increased risks of myocarditis and pericarditis, particularly within the period 0 through 7 days following the second dose of the primary series. The observed risk is higher among adolescent males and adult 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 ).

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

Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Pfizer-BioNTech COVID-19 Vaccine.

Limitation of Effectiveness

Pfizer-BioNTech COVID-19 Vaccine may not protect all vaccine recipients.

Adverse Reactions

Adverse Reactions in Clinical Trials

Adverse reactions following administration of the Pfizer-BioNTech COVID-19 Vaccine that have been reported in clinical trials include injection site pain, fatigue, headache, muscle pain, chills, joint pain, fever, injection site swelling, injection site redness, nausea, malaise, lymphadenopathy, decreased appetite, rash, and pain in extremity (see Full EUA Prescribing Information ) .

Adverse Reactions Identified in Post Authorization Experience

Severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema), diarrhea, vomiting, pain in extremity (arm), syncope, and dizziness have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.

Myocarditis and pericarditis have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.

Additional adverse reactions, some of which may be serious, may become apparent with more widespread use of the Pfizer-BioNTech COVID-19 Vaccine.

Use with Other Vaccines

There is no information on the co-administration of the Pfizer-BioNTech COVID-19 Vaccine with other vaccines.

INFORMATION TO PROVIDE TO VACCINE RECIPIENTS/CAREGIVERS

As the vaccination provider, you must communicate to the recipient or their caregiver, information consistent with the "Vaccine Information Fact Sheet for Recipients and Caregivers" (and provide a copy or direct the individual to the website www.cvdvaccine.com to obtain the Vaccine Information Fact Sheet for Recipients and Caregivers) prior to the individual receiving each dose of the Pfizer-BioNTech COVID-19 Vaccine, including:

For information on clinical trials that are testing the use of the Pfizer-BioNTech COVID-19 Vaccine to prevent COVID-19, please see www.clinicaltrials.gov .

Provide a vaccination card to the recipient or their caregiver with the date when the recipient needs to return for the second dose of Pfizer-BioNTech COVID-19 Vaccine.

Provide the v-safe information sheet to vaccine recipients/caregivers and encourage vaccine recipients to participate in v-safe. V-safe is a new voluntary smartphone-based tool that uses text messaging and web surveys to check in with people who have been vaccinated to identify potential side effects after COVID-19 vaccination. V-safe asks questions that help CDC monitor the safety of COVID-19 vaccines. V-safe also provides dose reminders if needed and live telephone follow-up by CDC if participants report a significant health impact following COVID-19 vaccination. For more information, visit: www.cdc.gov/vsafe .

MANDATORY REQUIREMENTS FOR PFIZER-BIONTECH COVID-19 VACCINE ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION 4

In order to mitigate the risks of using this unapproved product under EUA and to optimize the potential benefit of Pfizer-BioNTech COVID-19 Vaccine, the following items are required. Use of unapproved Pfizer-BioNTech COVID-19 Vaccine for active immunization to prevent COVID-19 under this EUA is limited to the following (all requirements must be met):

* Serious adverse events are defined as:

OTHER ADVERSE EVENT REPORTING TO VAERS AND PFIZER INC.

Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.

To the extent feasible, report adverse events to Pfizer Inc. using the contact information below or by providing a copy of the VAERS form to Pfizer Inc.

ADDITIONAL INFORMATION

For general questions, visit the website or call the telephone number provided below.

To access the most recent Pfizer-BioNTech COVID-19 Vaccine Fact Sheets, please scan the QR code provided below.

AVAILABLE ALTERNATIVES

COMIRNATY (COVID-19 Vaccine, mRNA) and SPIKEVAX (COVID-19 Vaccine, mRNA) are FDA-approved vaccines to prevent COVID-19 caused by SARS-CoV-2. There may be clinical trials or availability under EUA of other COVID-19 vaccines.

COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine intended for individuals 12 years of age and older should not be used for individuals 6 months through 11 years of age because of the potential for vaccine administration errors, including dosing errors.

FEDERAL COVID-19 VACCINATION PROGRAM

This vaccine is being made available for emergency use exclusively through the CDC COVID-19 Vaccination Program (the Vaccination Program). Healthcare providers must enroll as providers in the Vaccination Program and comply with the provider requirements. Vaccination providers may not charge any fee for the vaccine and may not charge the vaccine recipient any out-of-pocket charge for administration. However, vaccination providers may seek appropriate reimbursement from a program or plan that covers COVID-19 vaccine administration fees for the vaccine recipient (private insurance, Medicare, Medicaid, Health Resources & Services Administration [HRSA] COVID-19 Uninsured Program for non-insured recipients). For information regarding provider requirements and enrollment in the CDC COVID-19 Vaccination Program, see https://www.cdc.gov/vaccines/covid-19/provider-enrollment.html .

Individuals becoming aware of any potential violations of the CDC COVID-19 Vaccination Program requirements are encouraged to report them to the Office of the Inspector General, U.S. Department of Health and Human Services, at 1-800-HHS-TIPS or https://TIPS.HHS.GOV .

AUTHORITY FOR ISSUANCE OF THE EUA

The Secretary of Health and Human Services (HHS) has declared a public health emergency that justifies the emergency use of drugs and biological products during the COVID-19 pandemic. In response, FDA has issued an EUA for the unapproved product, Pfizer-BioNTech COVID-19 Vaccine, and for certain uses of FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) for active immunization to prevent COVID-19.

FDA issued this EUA, based on Pfizer-BioNTech's request and submitted data.

For the authorized uses, although limited scientific information is available, based on the totality of the scientific evidence available to date, it is reasonable to believe that the Pfizer-BioNTech COVID-19 Vaccine and COMIRNATY (COVID-19 Vaccine, mRNA) may be effective for the prevention of COVID-19 in individuals as specified in the Full EUA Prescribing Information .

This EUA for the Pfizer-BioNTech COVID-19 Vaccine and COMIRNATY (COVID-19 Vaccine, mRNA) will end when the Secretary of HHS determines that the circumstances justifying the EUA no longer exist or when there is a change in the approval status of the product such that an EUA is no longer needed.

For additional information about Emergency Use Authorization visit FDA at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization .

The Countermeasures Injury Compensation Program

The Countermeasures Injury Compensation Program (CICP) is a federal program that has been created to help pay for related costs of medical care and other specific expenses to compensate people injured after use of certain medical countermeasures. Medical countermeasures are specific vaccines, medications, devices, or other items used to prevent, diagnose, or treat the public during a public health emergency or a security threat. For more information about CICP regarding the Pfizer-BioNTech COVID-19 Vaccine used to prevent COVID-19, visit www.hrsa.gov/cicp/ , email [email protected] , or call: 1-855-266-2427.

Manufactured for BioNTech Manufacturing GmbH An der Goldgrube 12 55131 Mainz, Germany

LAB-1450-31.0

Revised: 22 December 2022

END SHORT VERSION FACT SHEET

Long Version (Full EUA Prescribing Information) Begins On Next Page

FULL EMERGENCY USE AUTHORIZATION (EUA) PRESCRIBING INFORMATION

1 AUTHORIZED USE

Pfizer-BioNTech COVID-19 Vaccine is authorized for use under an Emergency Use Authorization (EUA) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months of age and older.

This EUA Prescribing Information pertains only to Pfizer-BioNTech COVID-19 Vaccine supplied in a multiple dose vial with a purple cap, which is authorized for use in individuals 12 years of age and older.

2 DOSAGE AND ADMINISTRATION

For intramuscular injection only.

The storage, preparation, and administration information in this Prescribing Information apply to the Pfizer-BioNTech COVID-19 Vaccine for individuals 12 years of age and older, which is supplied in a multiple dose vial with a purple cap and MUST BE DILUTED before use.

2.1 Preparation for Administration

2.2 administration information, 2.3 vaccination schedule.

Primary Series 5

The Pfizer-BioNTech COVID-19 Vaccine is administered intramuscularly as a primary series of 2 doses (0.3 mL each) 3 weeks apart in individuals 12 years of age and older.

A third primary series dose of the Pfizer-BioNTech COVID-19 Vaccine (0.3 mL) at least 28 days following the second dose is authorized for administration to individuals at least 12 years of age with certain kinds of immunocompromise. 6

3 DOSAGE FORMS AND STRENGTHS

Pfizer-BioNTech COVID-19 Vaccine is a suspension for injection.

After preparation, each dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in vials with purple caps is 0.3 mL for individuals 12 years of age and older [see Dosage and Administration (2.1) ] .

4 CONTRAINDICATIONS

Do not administer Pfizer-BioNTech COVID-19 Vaccine to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 Vaccine [see Description (13) ] .

5 WARNINGS AND PRECAUTIONS

5.1 management of acute allergic reactions, 5.2 myocarditis and pericarditis, 5.3 syncope, 5.4 altered immunocompetence, 5.5 limitation of effectiveness.

The Pfizer-BioNTech COVID-19 Vaccine may not protect all vaccine recipients.

6 OVERALL SAFETY SUMMARY

It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of myocarditis, cases of pericarditis, cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and hospitalized or fatal cases of COVID-19 following vaccination with the Pfizer-BioNTech COVID-19 Vaccine. 7 To the extent feasible, provide a copy of the VAERS form to Pfizer Inc. Please see the REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS section for details on reporting to VAERS and Pfizer Inc.

In clinical studies of participants 16 years of age and older who received Pfizer-BioNTech COVID-19 Vaccine containing 30 mcg of a nucleoside-modified messenger RNA encoding the viral spike (S) glycoprotein of SARS-CoV-2 (30 mcg modRNA), adverse reactions following administration of the primary series included pain at the injection site (84.1%), fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%), fever (14.2%), injection site swelling (10.5%), injection site redness (9.5%), nausea (1.1%), malaise (0.5%), and lymphadenopathy (0.3%).

In a clinical study in adolescents 12 through 15 years of age who received Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA), adverse reactions following administration of the primary series included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%).

Post Authorization Experience

Severe allergic reactions, including anaphylaxis, have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of the primary series Pfizer-BioNTech COVID-19 Vaccine was evaluated in participants 12 years of age and older in two 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 or older. Of these, approximately 43,448 participants [21,720 Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2; 21,728 placebo] in Phase 2/3 are 16 years of age or older (including 138 and 145 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively) and 2,260 adolescents are 12 through 15 years of age (1,131 and 1,129 in the vaccine and placebo groups, respectively).

In Study 2, all participants 12 through 15 years of age, and 16 years of age 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]. Tables 1 through 6 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of Pfizer-BioNTech COVID 19 Vaccine and placebo.

Participants 16 Years of Age and Older

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.

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.

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 7960 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.

Adolescents 12 Through 15 Years of Age

In an analysis of Study 2, based on data up to the cutoff date of March 13, 2021, 2,260 adolescents (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) adolescents 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 adolescents who received Pfizer-BioNTech COVID-19 Vaccine and those who received placebo. Overall, among the adolescents 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.

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 adolescents in the Pfizer-BioNTech COVID-19 Vaccine group.

In the following analyses of Study 2 in adolescents 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 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 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.

6.2 Post Authorization Experience

The following adverse reactions have been identified during post authorization use of Pfizer-BioNTech COVID-19 Vaccine. Because these reactions are reported voluntarily, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.

Cardiac Disorders: myocarditis, pericarditis

Gastrointestinal Disorders: diarrhea, vomiting

Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema)

Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)

Nervous System Disorders: syncope, dizziness

8 REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS 8

See Overall Safety Summary (Section 6) for additional information.

The vaccination provider enrolled in the federal COVID-19 Vaccination Program is responsible for MANDATORY reporting of the listed events following Pfizer-BioNTech COVID-19 Vaccine to the Vaccine Adverse Event Reporting System (VAERS):

Instructions for Reporting to VAERS

The vaccination provider enrolled in the federal COVID-19 Vaccination Program should complete and submit a VAERS form to FDA using 1 of the following methods:

IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

The following steps are highlighted to provide the necessary information for safety tracking:

Other Reporting Instructions

10 DRUG INTERACTIONS

There are no data to assess the concomitant administration of the Pfizer-BioNTech COVID-19 Vaccine with other vaccines.

11 USE IN SPECIFIC POPULATIONS

11.1 pregnancy.

Risk Summary

All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on Pfizer-BioNTech COVID-19 Vaccine administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

In a reproductive and developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (modRNA) (30 mcg) and other ingredients included in a single human dose of Pfizer-BioNTech COVID-19 Vaccine was administered to female rats by the intramuscular route on 4 occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.

11.2 Lactation

Data are not available to assess the effects of Pfizer-BioNTech COVID-19 Vaccine on the breastfed infant or on milk production/excretion.

11.3 Pediatric Use

Pfizer-BioNTech COVID-19 Vaccine is authorized for use in individuals 6 months through 17 years of age. This authorization is based on safety and effectiveness data in this age group and adults.

Pfizer-BioNTech COVID-19 Vaccine is not authorized for use in individuals younger than 6 months of age.

11.4 Geriatric Use

Clinical studies of Pfizer-BioNTech COVID-19 Vaccine include participants 65 years of age and older who received the primary series and their data contributes to the overall assessment of safety and efficacy [see Overall Safety Summary (6.1) and Clinical Trial Results and Supporting Data for EUA (18.1) ] . Of the total number of Pfizer-BioNTech COVID-19 Vaccine recipients in Study 2 (N=20,033), 21.4% (n=4,294) were 65 years of age and older and 4.3% (n=860) were 75 years of age and older.

11.5 Use in Immunocompromised

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) , safety and effectiveness of a third dose of the Pfizer-BioNTech COVID-19 vaccine have been evaluated in persons that received solid organ transplants. The administration of a third dose of vaccine appears to be only moderately effective in increasing potentially protective antibody titers. Patients should still be counselled to maintain physical precautions to help prevent COVID-19. In addition, close contacts of immunocompromised persons should be vaccinated as appropriate for their health status.

13 DESCRIPTION

The Pfizer-BioNTech COVID-19 Vaccine is supplied as a frozen suspension in multiple dose vials with purple caps; each vial must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine. Each 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with purple caps contains 30 mcg of a nucleoside-modified messenger RNA (modRNA) encoding the viral spike (S) glycoprotein of the SARS-CoV-2 Wuhan-Hu-1 strain.

Each 0.3 mL dose of the Pfizer-BioNTech COVID-19 Vaccine supplied in multiple dose vials with purple caps also includes the following ingredients: lipids (0.43 mg ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.2 mg cholesterol), 0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 0.07 mg dibasic sodium phosphate dihydrate, and 6 mg sucrose. The diluent (sterile 0.9% Sodium Chloride Injection, USP) contributes an additional 2.16 mg sodium chloride per dose.

The Pfizer-BioNTech COVID-19 Vaccine does not contain preservative. The vial stoppers are not made with natural rubber latex.

14 CLINICAL PHARMACOLOGY

14.1 mechanism of action.

The modRNA in the Pfizer-BioNTech COVID-19 Vaccine is formulated in lipid particles, which enable delivery of the RNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.

18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

18.1 efficacy of primary series in participants 16 years of age and older.

Study 2 is a multicenter, multinational, Phase 1/2/3, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate-selection, and efficacy study in participants 12 years of age and older. Randomization was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19. Participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, were included as were participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV).

In the Phase 2/3 portion of Study 2, based on data accrued through November 14, 2020, approximately 44,000 participants 12 years of age and older were randomized equally and received 2 doses of Pfizer-BioNTech COVID-19 Vaccine (30 mcg modRNA) or placebo separated by 21 days. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.

The population for the analysis of the primary efficacy endpoint included, 36,621 participants 12 years of age and older (18,242 in the Pfizer-BioNTech COVID-19 Vaccine group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. Table 7 presents the specific demographic characteristics in the studied population.

Human Immunodeficiency Virus (HIV) infection (not included in the efficacy evaluation)

The population in the primary efficacy analysis included all participants 12 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 through November 14, 2020. Participants 18 through 55 years of age and 56 years of age and older began enrollment from July 27, 2020, 16 through 17 years of age began enrollment from September 16, 2020, and 12 through 15 years of age began enrollment from October 15, 2020.

The vaccine efficacy information is presented in Table 8.

18.2 Efficacy of Primary Series in Adolescents 12 Through 15 Years of Age

A descriptive efficacy analysis of Study 2 has been performed in approximately 2,200 adolescents 12 through 15 years of age evaluating confirmed COVID-19 cases accrued up to a data cutoff date of March 13, 2021.

The efficacy information in adolescents 12 through 15 years of age is presented in Table 9.

18.3 Immunogenicity of Primary Series in Adolescents 12 Through 15 Years of Age

In Study 2, an analysis of SARS-CoV-2 50% neutralizing titers (NT50) 1 month after Dose 2 in a randomly selected subset of participants demonstrated non-inferior immune responses (within 1.5-fold) comparing adolescents 12 through 15 years of age to participants 16 through 25 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to 1 month after Dose 2 (Table 10).

18.4 Immunogenicity of a 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) , a single arm study has been conducted in 101 individuals who had undergone various solid organ transplant procedures (heart, kidney, liver, lung, pancreas) 97±8 months previously. A third dose of the Pfizer-BioNTech COVID-19 vaccine was administered to 99 of these individuals approximately 2 months after they had received a second dose. Among the 59 patients who had been seronegative before the third dose, 26 (44%) were seropositive at 4 weeks after the third dose. All 40 patients who had been seropositive before the third dose were still seropositive 4 weeks later. The prevalence of anti-SARS-CoV-2 antibodies was 68% (67 of 99 patients) 4 weeks after the third dose.

19 HOW SUPPLIED/STORAGE AND HANDLING

The information in this section applies to the Pfizer-BioNTech COVID-19 Vaccine that is supplied in multiple dose vials with a purple cap. These multiple dose vials are supplied in a carton containing 25 multiple dose vials (NDC 59267-1000-3) or 195 multiple dose vials (NDC 59267-1000-2). After dilution, 1 vial contains 6 doses of 0.3 mL. Vial labels and cartons may state that after dilution, a vial contains 5 doses of 0.3 mL. The information in this Full EUA Prescribing Information regarding the number of doses per vial after dilution supersedes the number of doses stated on vial labels and cartons.

If not stored between -90ºC to -60ºC (-130ºF to -76ºF), vials may be stored at -25°C to -15°C (-13°F to 5°F) for up to 2 weeks. Vials must be kept frozen and protected from light, in the original cartons, until ready to use. Vials stored at -25°C to -15°C (-13°F to 5°F) for up to 2 weeks may be returned one time to the recommended storage condition of -90ºC to -60ºC (-130ºF to -76ºF). Total cumulative time the vials are stored at -25°C to -15°C (-13°F to 5°F) should be tracked and should not exceed 2 weeks.

For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for 30 minutes. Thawed vials can be handled in room light conditions.

Vials must reach room temperature before dilution.

After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within 6 hours from the time of dilution. During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. Any vaccine remaining in vials must be discarded after 6 hours. Do not refreeze.

20 PATIENT COUNSELING INFORMATION

Advise the recipient or caregiver to read the Vaccine Information Fact Sheet for Recipients and Caregivers.

The vaccination provider must include vaccination information in the state/local jurisdiction's Immunization Information System (IIS) or other designated system. Advise recipient or caregiver that more information about IISs can be found at: https://www.cdc.gov/vaccines/programs/iis/about.html .

21 CONTACT INFORMATION

This Full EUA Prescribing Information may have been updated. For the most recent Full EUA Prescribing Information, please see www.cvdvaccine.com .

Manufactured by Pfizer Inc., New York, NY 10017

LAB-1457-30.0

VACCINE INFORMATION FACT SHEET FOR RECIPIENTS AND CAREGIVERS ABOUT COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, AND THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT (ORIGINAL AND OMICRON BA.4/BA.5) TO PREVENT CORONAVIRUS DISEASE 2019 (COVID-19) FOR USE IN INDIVIDUALS 12 YEARS OF AGE AND OLDER

You are being offered either COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5), hereafter referred to as the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, to prevent Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2.

This Vaccine Information Fact Sheet for Recipients and Caregivers comprises the Fact Sheet for the authorized Pfizer-BioNTech COVID-19 Vaccine and the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, and also includes information about the U.S. Food and Drug Administration (FDA)-licensed vaccine, COMIRNATY (COVID-19 Vaccine, mRNA) for use in individuals 12 years of age and older 9 .

The FDA-approved COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine authorized under Emergency Use Authorization (EUA) for individuals 12 years of age and older, when prepared according to their respective instructions for use, can be used interchangeably. 10

COMIRNATY (COVID-19 Vaccine, mRNA) is an FDA-approved COVID-19 vaccine made by Pfizer for BioNTech. It is approved as a 2-dose series for prevention of COVID-19 in individuals 12 years of age and older. It is also authorized under EUA to provide:

The Pfizer-BioNTech COVID-19 Vaccine has received EUA from FDA to provide:

The Pfizer-BioNTech COVID-19 Vaccine, Bivalent has received EUA from FDA to provide either:

This Vaccine Information Fact Sheet contains information to help you understand the risks and benefits of COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, and the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, which you may receive because there is currently a pandemic of COVID-19. Talk to your vaccination provider if you have questions.

This Fact Sheet may have been updated. For the most recent Fact Sheet, please see www.cvdvaccine.com .

WHAT YOU NEED TO KNOW BEFORE YOU GET ANY OF THESE VACCINES

WHAT IS COVID-19?

COVID-19 disease is caused by a coronavirus called SARS-CoV-2. You can get COVID-19 through contact with another person who has the virus. It is predominantly a respiratory illness that can affect other organs. People with COVID-19 have had a wide range of symptoms reported, ranging from mild symptoms to severe illness leading to death. Symptoms may appear 2 to 14 days after exposure to the virus. Symptoms may include: fever or chills; cough; shortness of breath; fatigue; muscle or body aches; headache; new loss of taste or smell; sore throat; congestion or runny nose; nausea or vomiting; diarrhea.

HOW ARE COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, AND THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT RELATED?

COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine, when prepared according to their respective instructions for use, can be used interchangeably. The Pfizer-BioNTech COVID-19 Vaccine, Bivalent is made in the same way as COMIRNATY and Pfizer-BioNTech COVID-19 Vaccine but it also contains an Omicron component to help prevent COVID-19 caused by the Omicron variant of SARS-CoV-2.

For more information on EUA, see the " What is an Emergency Use Authorization (EUA)? " section at the end of this Fact Sheet.

WHAT SHOULD YOU MENTION TO YOUR VACCINATION PROVIDER BEFORE YOU GET ANY OF THESE VACCINES?

Tell the vaccination provider about all of your medical conditions, including if you:

HOW ARE THESE VACCINES GIVEN?

The Pfizer-BioNTech COVID-19 Vaccine, the Pfizer-BioNTech COVID-19 Vaccine, Bivalent, or COMIRNATY (COVID-19 Vaccine, mRNA) will be given to you as an injection into the muscle.

Primary Series: The Pfizer-BioNTech COVID-19 Vaccine and COMIRNATY (COVID-19 Vaccine, mRNA) are given for the primary series. The vaccine is administered as a 2-dose series, 3 weeks apart. A third primary series dose may be administered at least 4 weeks after the second dose to individuals with certain kinds of immunocompromise.

Booster Dose: Pfizer-BioNTech COVID-19 Vaccine, Bivalent is administered as a single booster dose at least 2 months after:

The vaccine may not protect everyone.

WHO SHOULD NOT GET COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT?

You should not get any of these vaccines if you:

WHAT ARE THE INGREDIENTS IN THESE VACCINES?

COMIRNATY (COVID-19 Vaccine, mRNA), Pfizer-BioNTech COVID-19 Vaccine, and Pfizer-BioNTech COVID-19 Vaccine, Bivalent include the following ingredients:

Pfizer-BioNTech COVID-19 Vaccine for individuals 12 years of age and older contains 1 of the following sets of additional ingredients; ask the vaccination provider which version is being administered:

Pfizer-BioNTech COVID-19 Vaccine, Bivalent for individuals 12 years of age and older contains the following additional ingredients:

COMIRNATY (COVID-19 Vaccine, mRNA) contains 1 of the following sets of additional ingredients; ask the vaccination provider which version is being administered:

HAVE THESE VACCINES BEEN USED BEFORE?

In clinical trials, approximately 23,000 individuals 12 years of age and older have received at least 1 dose of Pfizer-BioNTech COVID-19 Vaccine. Millions of individuals have received the Pfizer-BioNTech COVID-19 Vaccine under EUA since December 11, 2020.

In a clinical trial, approximately 300 individuals greater than 55 years of age received one dose of a bivalent vaccine that differs from the Pfizer-BioNTech COVID-19 Vaccine, Bivalent in that it contains a different Omicron component.

WHAT ARE THE BENEFITS OF THESE VACCINES?

COMIRNATY (COVID-19 Vaccine, mRNA) and the Pfizer-BioNTech COVID-19 Vaccine have been shown to prevent COVID-19. FDA has authorized Pfizer-BioNTech COVID-19 Vaccine, Bivalent to provide better protection against COVID-19 caused by the Omicron variant of SARS-CoV-2.

The duration of protection against COVID-19 is currently unknown.

WHAT ARE THE RISKS OF THESE VACCINES?

There is a remote chance that these vaccines could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to 1 hour after getting a dose. For this reason, your vaccination provider may ask you to stay at the place where you received your vaccine for monitoring after vaccination. Signs of a severe allergic reaction can include:

Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received COMIRNATY (COVID-19 Vaccine, mRNA) or Pfizer-BioNTech COVID-19 Vaccine, more commonly in adolescent males and adult males under 40 years of age than among females and older males. In most of these people, symptoms began within a few days following receipt of the second dose of vaccine. The chance of having this occur is very low. You should seek medical attention right away if you have any of the following symptoms after receiving the vaccine:

Side effects that have been reported with these vaccines include:

These may not be all the possible side effects of these vaccines. Serious and unexpected side effects may occur. The possible side effects of these vaccines are still being studied.

WHAT SHOULD I DO ABOUT SIDE EFFECTS?

If you experience a severe allergic reaction, call 9-1-1, or go to the nearest hospital.

Call the vaccination provider or your healthcare provider if you have any side effects that bother you or do not go away.

Report vaccine side effects to FDA/CDC Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1-800-822-7967 or report online to https://vaers.hhs.gov/reportevent.html . Please include either "COMIRNATY (COVID-19 Vaccine, mRNA)", "Pfizer-BioNTech COVID-19 Vaccine EUA", or "Pfizer-BioNTech COVID-19 Vaccine, Bivalent EUA" as appropriate, in the first line of box #18 of the report form.

In addition, you can report side effects to Pfizer Inc. at the contact information provided below.

You may also be given an option to enroll in v-safe. V-safe is a voluntary smartphone-based tool that uses text messaging and web surveys to check in with people who have been vaccinated to identify potential side effects after COVID-19 vaccination. V-safe asks questions that help CDC monitor the safety of COVID-19 vaccines. V-safe also provides second-dose reminders if needed and live telephone follow-up by CDC if participants report a significant health impact following COVID-19 vaccination. For more information on how to sign up, visit: www.cdc.gov/vsafe .

WHAT IF I DECIDE NOT TO GET COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT?

Under the EUA, it is your choice to receive or not receive any of these vaccines. Should you decide not to receive any of these vaccines, it will not change your standard medical care.

ARE OTHER CHOICES AVAILABLE FOR PREVENTING COVID-19 BESIDES COMIRNATY (COVID-19 VACCINE, mRNA), THE PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT?

For primary vaccination, another choice for preventing COVID-19 is SPIKEVAX (COVID-19 Vaccine, mRNA), an FDA-approved COVID-19 vaccine. Other vaccines to prevent COVID-19 may be available under EUA, including bivalent vaccines that contain an Omicron component of SARS-CoV-2.

CAN I RECEIVE COMIRNATY (COVID-19 VACCINE, mRNA), PFIZER-BIONTECH COVID-19 VACCINE, OR THE PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT AT THE SAME TIME AS OTHER VACCINES?

Data have not yet been submitted to FDA on administration of COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent at the same time with other vaccines. If you are considering receiving COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent with other vaccines, discuss your options with your healthcare provider.

WHAT IF I AM IMMUNOCOMPROMISED?

If you are immunocompromised, you may receive a third primary series dose of Pfizer-BioNTech COVID-19 Vaccine or COMIRNATY (COVID-19 Vaccine, mRNA). Individuals 12 years of age and older may receive a booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent. Vaccinations may not provide full immunity to COVID-19 in people who are immunocompromised, and you should continue to maintain physical precautions to help prevent COVID-19. Your close contacts should be vaccinated as appropriate.

WHAT IF I AM PREGNANT OR BREASTFEEDING?

If you are pregnant or breastfeeding, discuss your options with your healthcare provider.

WILL THESE VACCINES GIVE ME COVID-19?

No. These vaccines do not contain SARS-CoV-2 and cannot give you COVID-19.

KEEP YOUR VACCINATION CARD

When you get your first COVID-19 vaccine, you will get a vaccination card. Remember to bring your card when you return.

If you have questions, visit the website or call the telephone number provided below.

To access the most recent Fact Sheets, please scan the QR code provided below.

HOW CAN I LEARN MORE?

WHERE WILL MY VACCINATION INFORMATION BE RECORDED?

The vaccination provider may include your vaccination information in your state/local jurisdiction's Immunization Information System (IIS) or other designated system. For more information about IISs visit: https://www.cdc.gov/vaccines/programs/iis/about.html .

CAN I BE CHARGED AN ADMINISTRATION FEE FOR RECEIPT OF THESE COVID-19 VACCINES?

No. At this time, the provider cannot charge you for a vaccine dose and you cannot be charged an out-of-pocket vaccine administration fee or any other fee if only receiving a COVID-19 vaccination. However, vaccination providers may seek appropriate reimbursement from a program or plan that covers COVID-19 vaccine administration fees for the vaccine recipient (private insurance, Medicare, Medicaid, Health Resources & Services Administration [HRSA] COVID-19 Uninsured Program for non-insured recipients).

WHERE CAN I REPORT CASES OF SUSPECTED FRAUD?

WHAT IS THE COUNTERMEASURES INJURY COMPENSATION PROGRAM?

The Countermeasures Injury Compensation Program (CICP) is a federal program that may help pay for costs of medical care and other specific expenses of certain people who have been seriously injured by certain medicines or vaccines, including these vaccines. Generally, a claim must be submitted to the CICP within one (1) year from the date of receiving the vaccine. To learn more about this program, visit http://www.hrsa.gov/cicp/ or call 1-855-266-2427.

WHAT IS AN EMERGENCY USE AUTHORIZATION (EUA)?

An EUA is a mechanism to facilitate the availability and use of medical products, including vaccines, during public health emergencies, such as the current COVID-19 pandemic. An EUA is supported by a Secretary of Health and Human Services (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic. A product authorized for emergency use has not undergone the same type of review by FDA as an FDA-approved product.

FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, and available alternatives. In addition, the FDA decision is based on the totality of the scientific evidence available showing that the product may be effective to prevent COVID-19 during the COVID-19 pandemic and that the known and potential benefits of the product outweigh the known and potential risks of the product. All of these criteria must be met to allow for the product to be used during the COVID-19 pandemic.

An EUA is in effect for the duration of the COVID-19 EUA declaration justifying emergency use of this product, unless terminated or revoked (after which the product may no longer be used).

LAB-1451-24.0

Revised: 8 December 2022

Revised: 12/2022 Document Id: 1631414e-abce-4853-989b-2d0085a79941 53404-0 Set id: 908ecbe7-2f1b-42dd-94bf-f917ec3c5af8 Version: 41 Effective Time: 20221229   Pfizer Manufacturing Belgium NV

• The A.V. Club
• The Takeout
• The Inventory

What page 132 of the Pfizer “vaccine report” actually says about infertility

The first thing to know about page 132 of the Pfizer vaccine report is that it doesn’t exist.

Or rather it does, but it contains just a few rows of abbreviations included in Pfizer’s clinical trial protocol for the Covid-19 vaccine invented by BioNTech. The version of page 132 circulating on corners of the internet —which doubts the Pfizer vaccine’s safety specifically for pregnant people— is not from Pfizer’s report. It’s a screenshot from a pdf of the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) guidance for healthcare professionals. (You can find the HTML here and the pdf version here) .

In the actual Pfizer study protocols , p.123-126 cover people of childbearing age. However, they don’t outline risks to fertility: They detail protocols Pfizer took to ensure that no one in the trial became pregnant, or contributed to a pregnancy, because that wasn’t the intent of its study. Pfizer didn’t want to include anyone expecting in that clinical trial; at that stage in the  studying the new Covid-19 vaccine, it’d be unethical to do so.

The words of warning around the screenshots of these documents—that the Pfizer/BioNTech vaccine causes widespread “infertility” and “birth defects due to genetic manipulation”—are false. There is no evidence to support those claims. Facebook, to its credit, has flagged at least one of these wide-reaching posts as misinformation. What the screenshots do highlight is the fact that there are still unanswered research questions about Covid-19 vaccines, even though governments have given them a cautious green light. It’s a perfect example of what scientists know and don’t know about the newly authorized Covid-19 vaccines.

It’s perfectly normal—and even encouraged—to have questions about a new vaccine, especially when it’ll likely reach you and 7 billion of your closest friends. Quartz is here to break down these concerns.

What does the Pfizer study protocol say about people who could become pregnant or contribute to a pregnancy?

The protocols say that people who make sperm can be included in the clinical trial if they agree to abstain from heterosexual sex for a month after their final dose or use a condom, and not to donate sperm for that time.

It also states that people who could become pregnant can participate if they agree to abstain from heterosexual sex or are using a list of approved birth controls (which includes everything but the pull-out or rhythm method). Healthcare professionals conducting the clinical trial are advised to screen anyone who could become pregnant about  their sexual activity and last periods to rule out an undetected early pregnancy. Pfizer states that the reason for these precautions is to “eliminate reproductive safety risk of the study intervention”—which  translates to avoiding any possible risk in the absence of concrete data assuring the vaccine’s safety for pregnant people.

What does the UK’s MHRA say about Covid-19 vaccines and fertility?

In its guidance to healthcare providers administering vaccines, the MHRA states that the Pfizer/BioNTech’s Covid-19 vaccine long-term effects on pregnancy and fertility hasn’t  been studied extensively.

These guidelines recommend that healthcare providers ensure that the people they vaccinate aren’t pregnant, and that they should not try to become pregnant up to two months after their second dose. This is not because the vaccine is suspected to be dangerous—it’s because there isn’t data supporting that it’s perfectly safe. Pregnancy already takes a massive toll on the body, and healthcare providers want to make absolutely sure they’re not adding to that in any way.

It also states that, because scientists aren’t sure if the vaccine can be secreted in breastmilk, nor if its safe in infants, people who are breastfeeding should abstain from getting the vaccine.

And it states, in plain language, that scientists don’t know if fertility can be impacted by the vaccine. That doesn’t mean, however, that it is inherently dangerous for fertility.

What data do we have around pregnancy from the Pfizer/BioNTech trials?

In the Phase 3 trial data that Pfizer/BioNTech submitted (pdf, p. 42) to global regulatory authorities, the companies explicitly stated that they did not  intend to test the vaccine on pregnant people. This is because it’s generally considered unethical to include pregnant people in clinical trials—at least at first.

In the trial, researchers required people who could be pregnant to take a quick pregnancy test; if it came up positive, they were not allowed to participate in the trial. Still, Pfizer and BioNTech report that 23 people became pregnant over the course of their trial; 12 of them received the vaccine, and 11 of them received the placebo. Two people suffered miscarriages, but both of them had received the placebo and not the vaccine. Twelve data points of pregnant people with the vaccine isn’t enough for scientists to say whether or not it’s safe for all pregnant people.

The review memo from the US Food and Drug Administration (FDA) granting the vaccine emergency use authorization in the US states (pdf p. 45) that Pfizer plans to conduct another clinical trial on pregnant people in the future. It also plans to continue a surveillance studies in general populations to assess its vaccine’s long-term safety.

Although we don’t have long-term data yet on vaccine’s safety for any group, previous studies have shown that mRNA (from ourselves, and from vaccines) breaks down within hours , which suggests that it likely won’t have any long-term effects. As a reminder, mRNA a vaccines cannot alter your own genetic material .

Why didn’t the companies study effects on fertility?

The primary endpoint of the Pfizer/BioNTech vaccine trials were to see if their vaccine candidates were safe for participants and effective at preventing cases of Covid-19, which is the disease caused by SARS-CoV-2. Importantly, they were  not  looking at whether the vaccine did other things, like prevent SARS-CoV-2 transmission entirely (which would be great!) or have other kinds of long-term effects on fertility.

These studies were designed to get an effective vaccine out to the public as fast as possible. This doesn’t mean that regulators cut corners. As Quartz’ has reported before , global authorities  resisted pressure to speed up the review timeline, knowing that people would be skeptical of a rushed trial. The vaccine’s effects on fertility—and other long-term questions—will be answered in ongoing surveillance studies, although scientists do not have reason to believe that could be going to be dangerous adverse events down the road.

Are the UK’s guidelines different from what the US Food and Drug Administration says?

Yes and no. The FDA is working with the same data as the MHRA, but has framed some of its answers to common questions about the Pfizer/BioNTech slightly differently.

In the same absence of concrete safety data for fertility and pregnancy, the US FDA has stated that although we don’t know if the vaccine could cause infertility, we also have no reason to believe that it could. It explains that mRNA vaccines do not contain the actual SARS-CoV-2 virus, nor any part of it, which is why it cannot impact fertility.

It then goes on to say that anyone spreading misinformation about the vaccine’s negative impacts on fertility is irresponsible, because they would be discouraging others from getting protection for a potentially life-threatening disease.

So is the vaccine safe for people who are pregnant? Or people who want to become pregnant?

As Quartz has reported before , no group recommends that people who are pregnant get the Covid-19 vaccine. However, in the US, American College of Obstetricians and Gynecologists and other groups have advocated that people who are pregnant should be able to access a Covid-19 if they want it. They also recommend that these individuals talk to their healthcare providers about whether the vaccine is right for them, given their other underlying health issues or lifestyles.

In the US, the lack of concrete evidence in favor of the vaccines’ safety in pregnant people, and lack of concrete concerns, are taken to mean that the risk is not great enough to avoid vaccination at all. In the UK, not  knowing for sure is deemed too great a risk to take on. Neither is a wrong approach—they’re just different. What’s important is that we all understand how each group came to these stances, and for you to be able to determine which level of risk you and your healthcare providers are most comfortable with.

Update (Dec. 31): This story has been updated to reflect p. 123-126 of the Pfizer report, which focus on trial participants of childbearing age.

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Pfizer-BioNTech COVID-19 Vaccine Reactions & Adverse Events

COVID-19 vaccine recommendations have been updated as of September 12. The content on this page is no longer current and will be updated to align with the new recommendations. Learn more .

Local Reactions

Systemic reactions, unsolicited adverse events, serious adverse events, persons aged 6 months – 4 years.

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

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

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

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

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

a  Mild: ≥0.5 to 2.0 cm; moderate: >2.0 to 7.0 cm; severe: >7.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only) b  Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization

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

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

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

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

a  Any fever= ≥38.0°C b Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization c Mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or hospitalization d Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours; Grade 4: emergency room visit or hospitalization

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

Serious adverse events were defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, or resulted in persistent disability or incapacity.

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

Persons Aged 5 – 11 Years

Among all study vaccine recipients aged 5–11 years, 86.2% reported at least one local injection site reaction in the 7 days after vaccination. Pain at the injection site was the most frequent and severe solicited local reaction among vaccine recipients and was slightly more common after dose 1. No grade 4 local reactions were reported. The median onset of local reactions in the vaccine group was 1 to 2 days after either dose and lasted a median duration between 1 and 2 days. ( Table 5 )

Table 5. Local reactions in persons aged 5–11 years, Pfizer-BioNTech COVID-19 vaccine and placebo

a Mild: >2.0 to 5.0 cm; moderate: >5.0 to 10.0 cm; severe: >10.0 cm; Grade 4: necrosis (redness and swelling categories) or exfoliative dermatitis (redness category only).

b Mild: does not interfere with activity; moderate: interferes with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe pain at the injection site.

Among all vaccine recipients, 66.6% reported at least one systemic reaction in the 7 days after vaccination. The frequency and severity of systemic adverse events was higher after dose 2 than dose 1. Fatigue, headache, chills, and new or worsened muscle pain were most common. The majority of systemic events were mild or moderate in severity, after both doses. Fever was more common after the second dose than after the first dose. Overall, the median onset of systemic adverse events in the vaccine group in general was 1 to 4 days after either dose and lasted a median duration of 1 day. One grade 4 fever (>40.0°C) was reported in the vaccine group. No other systemic grade 4 reactions were reported. ( Table 6 )

Table 6. Systemic reactions in persons aged 5–11 years, Pfizer-BioNTech COVID-19 vaccine and placebo

a  Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe fatigue, severe headache, severe muscle pain, or severe joint pain.

b  Mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or hospitalization for severe vomiting.

c  Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours; Grade 4: emergency room visit or hospitalization for severe diarrhea.

Reports of lymphadenopathy were imbalanced. Thirteen participants (0.9%) in the vaccine group and 1 participant (0.1%) in the placebo group had events of lymphadenopathy. The median time to onset was 2-3 days after either dose and all cases resolved within 2 weeks.

Among a safety expansion cohort (over 2250 children randomized 2:1 vaccine to placebo), 6 participants (0.4%) in the vaccine arm and 3 participants (0.4%) in the placebo arm had events of lymphadenopathy. No Bell’s palsy, anaphylaxis or myocarditis was reported among vaccine recipients in this age group.

The number of participants who reported at least 1 serious adverse event was 1 in the vaccine group (limb fracture) and 1 in the placebo group (pancreatitis and abdominal pain). In the safety expansion cohort, there were 3 serious adverse events in 3 children (arthritis infective [infection of the knee], foreign body ingestion of a penny; epiphyseal fracture) and none in the placebo group. No serious adverse events were considered as possibly related to the vaccine.

Data source: Comirnaty and Pfizer-BioNTech COVID-19 Vaccine | FDA

Persons Aged 12 – 15 Years

Among all study vaccine recipients aged 12–15 years, 90.9% reported at least one local injection site reaction in the 7 days after vaccination. Pain at the injection site was the most frequent and severe solicited local reaction among vaccine recipients and was slightly more common after dose 2. No grade 4 local reactions were reported. The median onset of local reactions in the vaccine group was 0 (day of vaccination) to 2 days after either dose and lasted a median duration between 1 and 3 days. This data is presented in Table 7 below.

Table 7. Local reactions in persons aged 12-15 years, Pfizer-BioNTech COVID-19 vaccine and placebo

Among all vaccine recipients, 90.7% reported at least one systemic reaction in the 7 days after vaccination. The frequency and severity of systemic adverse events was higher after dose 2 than dose 1. Vomiting and diarrhea were exceptions, and similar between vaccine and placebo groups and regardless of dose. Fatigue, headache, chills, and new or worsened muscle pain were most common. The majority of systemic events were mild or moderate in severity, after both doses. Fever was more common after the second dose than after the first dose. Overall, the median onset of systemic adverse events in the vaccine group in general was 1 to 3 days after either dose and lasted a median duration of 1 to 2 days. One grade 4 fever (>40.0°C) was reported in the vaccine group. No other systemic grade 4 reactions were reported. This data is presented in Table 8 below.

Table 8. Systemic reactions in persons aged 12-15 years, Pfizer-BioNTech COVID-19 vaccine and placebo

Reports of lymphadenopathy were imbalanced with 6 more cases in the vaccine group (7) than the placebo group (1); lymphadenopathy is plausibly related to the vaccine. Lymphadenopathy occurred in the arm and neck region and was reported within 2 to 4 days after vaccination. Most cases of lymphadenopathy resolved in 10 days or less. No bell’s palsy or anaphylaxis was reported among vaccine recipients in this age group.

The proportions of participants who reported at least 1 serious adverse event were 0.4% in the vaccine group and 0.2% in the placebo group. No serious adverse events were considered by FDA as possibly related to vaccine.

Data source: FDA Decision Memo

Persons Aged ≥18 Years

Among all study vaccine recipients asked to complete diaries of their symptoms during the 7 days after vaccination, 84.7% reported at least one local injection site reaction. By age group, 88.7% in the younger group (aged 18 to 55 years) and 79.7% in the older group (aged >55 years) reported at least one local reaction. Pain at the injection site was the most frequent and severe solicited local reaction among vaccine recipients. After dose 1, the younger age group reported pain more frequently than the older age group (83.1% vs 71.1%); a similar pattern was observed after dose 2 (77.8% vs 66.1%). Injection site redness and swelling following either dose were reported less frequently than injection site pain. Redness and swelling were slightly more common after dose 2. No grade 4 local reactions were reported. Overall, the median onset of local reactions in the vaccine group was 0 (day of vaccination) to 2 days after either dose and lasted a median duration between 1 and 2 days. Data on local reactions were not solicited from persons aged 16-17 years. However, their reactions to vaccination are expected to be similar to those of young adults who were included. In addition, reactogenicity data from adolescents aged 12-15 years were obtained and reviewed, and were similar to those from adults aged 18-55 years. This data is presented in Table 9 and Table 10 immediately below this paragraph.

Table 9. Local reactions in persons aged 18-55 years, Pfizer-BioNTech COVID-19 vaccine and placebo

Table 10. local reactions in persons aged >55 years, pfizer-biontech covid-19 vaccine and placebo.

Among all vaccine recipients asked to complete diaries of their symptoms during the 7 days after vaccination, 77.4% reported at least one systemic reaction. The frequency of systemic adverse events was higher in the younger than the older age group (82.8% vs 70.6%). Within each age group, the frequency and severity of systemic adverse events was higher after dose 2 than dose 1. Vomiting and diarrhea were exceptions, and similar between vaccine and placebo groups and regardless of dose. For both age groups, fatigue, headache and new or worsened muscle pain were most common. The majority of systemic events were mild or moderate in severity, after both doses and in both age groups. Fever was more common after the second dose and in the younger group (15.8%) compared to the older group (10.9%). Overall, the median onset of systemic adverse events in the vaccine group in general was 1 to 2 days after either dose and lasted a median duration of 1 day. Four grade 4 fevers (>40.0°C) were reported, two in the vaccine group and two in the placebo group. No other systemic grade 4 reactions were reported. Data on systemic reactions were not solicited from persons aged 16-17 years. However, their reactions to vaccination are expected to be similar to those of young adults who were included. In addition, reactogenicity data from adolescents aged 12-15 years were obtained and reviewed, and were similar to those from adults aged 18-55 years. This data is presented in Table 11 and Table 12 immediately below this paragraph.

Table 11. Systemic reactions in persons aged 18-55 years, Pfizer-BioNTech COVID-19 vaccine and placebo

a Mild: does not interfere with activity; moderate: some interference with activity; severe: prevents daily activity; Grade 4: emergency room visit or hospitalization for severe fatigue, severe headache, severe muscle pain, or severe joint pain.

b Mild: 1 to 2 times in 24 hours; moderate: >2 times in 24 hours; severe: requires intravenous hydration; Grade 4: emergency room visit or hospitalization for severe vomiting.

c Mild: 2 to 3 loose stools in 24 hours; moderate: 4 to 5 loose stools in 24 hours; severe: 6 or more loose stools in 24 hours; Grade 4: emergency room visit or hospitalization for severe diarrhea.

Table 12. Systemic reactions in persons aged >55 years, Pfizer-BioNTech COVID-19 vaccine and placebo

Reports of lymphadenopathy were imbalanced with 58 more cases in the vaccine group (64) than the placebo group (6); lymphadenopathy is plausibly related to the vaccine. Lymphadenopathy occurred in the arm and neck region and was reported within 2 to 4 days after vaccination. The average duration of lymphadenopathy was approximately 10 days. Bell’s palsy was reported by four vaccine recipients and none of the placebo recipients. The observed frequency of reported Bell’s palsy in the vaccine group is consistent with the background rate in the general population, and there is no basis upon which to conclude a causal relationship.

Serious adverse events were defined as any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, or resulted in persistent disability/incapacity. The proportions of participants who reported at least 1 serious adverse event were 0.6% in the vaccine group and 0.5% in the placebo group. The most common serious adverse events in the vaccine group which were numerically higher than in the placebo group were appendicitis (7 in vaccine vs 2 in placebo), acute myocardial infarction (3 vs 0), and cerebrovascular accident (3 vs 1). Cardiovascular serious adverse events were balanced between vaccine and placebo groups. Two serious adverse events were considered by U.S. Food and Drug Administration (FDA) as possibly related to vaccine: shoulder injury possibly related to vaccine administration or to the vaccine itself, and lymphadenopathy involving the axilla contralateral to the vaccine injection site. Otherwise, occurrence of severe adverse events involving system organ classes and specific preferred terms were balanced between vaccine and placebo groups.

Data source: FDA briefing document

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Side Effects of COVID-19 Pfizer-BioNTech mRNA Vaccine in Children Aged 12–18 Years in Saudi Arabia

Edrous alamer.

1 Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jazan University, Jazan 45142, Saudi Arabia; as.ude.unazaj@remalae (E.A.); moc.liamtoh@1qfiaan (N.A.Q.)

2 Emerging and Epidemic Infectious Diseases Research Unit, Medical Research Center, Jazan University, Jazan 45142, Saudi Arabia; as.ude.unazaj@imzahlaba (A.A.); moc.liamg@99remalafahar (R.A.); moc.liamtoh@ihseeraamilah (H.A.); as.ude.unazaj@irdaqm (M.Q.)

Abdulaziz Alhazmi

3 Microbiology and Parasitology Department, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia

Naaif A. Qasir

Rahaf alamer.

4 College of Medicine, Jazan University, Jazan 45142, Saudi Arabia

Halima Areeshi

Gassem gohal.

5 Department of Pediatrics, College of Medicine, Jazan University, Jazan 45142, Saudi Arabia; [email protected]

Marwa Qadri

6 Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia

Anwar M. Hashem

7 Department of Medical Microbiology and Parasitology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; as.ude.uak@mehsahma

8 Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia

Abdullah Algaissi

Associated data.

The dataset produced and analyzed in this study are available upon request from the corresponding author on reasonable request.

Background : Massive vaccination campaigns have been undertaken globally to combat the spread of the Coronavirus Disease 2019 (COVID-19). While most COVID-19 vaccines have shown excellent efficacy and safety profiles in clinical studies, real-world monitoring of vaccine safety is still important. In this study, we aimed to investigate the early side effects of Pfizer-BioNTech (BNT162b2) mRNA vaccine in children between 12–18 years old in Saudi Arabia. Method : To investigate the side effects in children in this age range following the administration of either one or two doses of Pfizer-BioNTech (BNT162b2) mRNA vaccine, we conducted a retrospective, cross-sectional study using a self-administered online survey. General and demographic data were collected, and vaccine-associated side effects following vaccination were evaluated. Results : The study recruited a total of 965 eligible participants. Overall, 571 (60%) of the study participants reported at least one side effect following Pfizer-BioNTech (BNT162b2) mRNA vaccination. The most frequently reported side effects were pain or redness at the site of injection (90%), fatigue (67%), fever (59%), headache (55%), nausea or vomiting (21%), and chest pain and shortness of breath (20%). Joint or bone pain were reported less frequently among our participants (2%). Our data showed that more female participants reported side effects compared to male participants, with 52% and 48%, respectively. Side effects were more common after the second dose compared to the first dose in our study cohort. Conclusions : While 60% of the children (12–18 years old) who received Pfizer-BioNTech (BNT162b2) mRNA vaccine reported side effects, our data showed that these side effects were not different from those that were reported in the clinical trials which lasted only for a few days. Side effects were more common after the second dose. Larger epidemiological and molecular studies are needed to evaluate the safety and the effectiveness of COVID-19 vaccine in protection of children against SARS-CoV-2 reinfections.

1. Introduction

Coronavirus Disease 2019 (COVID-19) is an ongoing global pandemic that is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) [ 1 ]. On 12th of March 2020, COVID-19 was declared as a global pandemic by the World Health Organization. Since then, more than 215 million confirmed cases and ~ 4.5 million deaths have been reported from all around the world [ 2 ]. SARS-CoV-2 infections can cause a wide variety of clinical manifestations that range from asymptomatic or mild to severe lung and multiorgan infections that can lead to death [ 3 ]. Notably, with the high transmission rates, new variants of SARS-CoV-2 have emerged, causing a new challenge in controlling this ongoing pandemic [ 4 , 5 ]. SARS-CoV-2 is a novel CoV that is classified within the subgenus Sarbecovirus of the genus Betacoronavirus genera, along with SARS-CoV-1 and a number of emerging animal and bat CoVs [ 1 ]. While the search for the origin of SARS-CoV-2 is still ongoing, it is believed that this virus originated from bats and was transmitted to an intermediate host before it spilled over into humans, in a scenario similar to the emergence of SARS-CoV-1 and MERS-CoV [ 6 , 7 ]. Like other CoVs, the genome of SARS-CoV-2 is approximately 30 kb in length and contains at least six open reading frames (ORFs) that encode for four main structural proteins (envelope (E), membrane (M), spike (S), and nucleocapsid (N) proteins) and up to 16 non-structural proteins (nsps), as well as other accessory proteins [ 8 ]. The S protein plays a critical role in attachment and entry of the virus to host cells because it contains the receptor-binding domain (RBD) that mediates virus binding to cellular receptors, and S2 which mediates fusion with cell membranes [ 9 ]. Because of this, the S protein is considered the major target for vaccine development against SARS-CoV-2 [ 10 ]. That is, almost all currently approved vaccines, including the Pfizer-BioNTech (BNT162b2) mRNA vaccine, target the S protein as an immunogen.

Vaccination is a crucial public health intervention method to control the spread of infectious diseases, including the ongoing COVID-19 pandemic [ 5 ]. Currently, nearly 190 COVID-19 vaccines are at different stages of pre-clinical and clinical development, with a few vaccines having been recently granted an Emergency Use Authorization (EUA) and are approved by WHO in many parts of the world. Among the currently approved COVID-19 vaccines are the Oxford/AstraZeneca AZD1222 and Janssen Ad26 CoV2.S which are based on non-replicating viral vector platforms; and Pfizer-BioNTech (BNT162b2) and Moderna mRNA-1273 which are based on messenger RNA (mRNA) technology [ 10 , 11 , 12 , 13 ].

Currently, substantial mass vaccination campaigns are underway worldwide to combat this ongoing pandemic. Globally, almost 5.5 billion doses of COVID-19 vaccines have been administered to date, with a rate of 33.54 million doses given on a daily basis [ 14 ]. Saudi Arabia was one of the first countries to initiate COVID-19 vaccination programs following approval of COVID-19 vaccines [ 15 ]. Among all other COVID-19 vaccines, the Pfizer-BioNTech COVID-19 mRNA vaccine was the first vaccine to receive approval in Saudi Arabia. The initial authorization for this vaccine was given for some high-risk and vulnerable groups, including healthcare workers and old people with chronic diseases. Thereafter, it became widely available for the whole population, excluding children and pregnant women [ 15 ]. However, recently, this vaccine was approved in Saudi Arabia for both pregnant women and children between the ages of 12–18 years, Table 1 [ 15 , 16 , 17 ]. As of October 10, 2021, there have been 44 million administered doses of COVID-19 vaccines in Saudi Arabia [ 17 ].

Approved and used COVID-19 vaccines in Saudi Arabia (data from the Saudi Public Health Authority [ 17 ]).

The Pfizer-BioNTech vaccine (BNT162b2) is based on mRNA technology to express the SARS-CoV-2 spike (S) gene [ 12 ]. The technology of mRNA vaccines has recently been introduced for its potential use in vaccine production, and some are on ongoing trials, such as vaccines against HIV and ZIKA virus [ 10 ]. However, Pfizer-BioNTech vaccine (BNT162b2) is considered the first mRNA-based vaccine for infectious diseases approved for human use [ 18 ]. BNT162b2 uses a carrier system based on lipid nanoparticles which is stabilized by a polyethylene glycol (PEG) 2000 lipid conjugate, providing a hydrophilic layer, extending its half-life [ 11 , 19 ]. Data from phase 3 trials revealed that two doses of BNT162b2 have a good safety profile and showed almost 95% efficacy rate against COVID-19 in persons 16 years of age or older [ 20 , 21 , 22 ]. Similarly, a phase 3 trial showed that BNT162b2 has favorable safety with transient mild-to-moderate reactogenicity and 100% efficacy rate in 12- to 15-year-old adolescents [ 21 ]. Like the older age group, the most predominant side effects reported in 12- to 15-year-old adolescents were injection-site pain (in 79 to 86% of participants), fatigue (in 60 to 66%), and headache (in 55 to 65%) [ 22 ]. Although data from clinical trials can demonstrate the efficacy and safety profiles of new vaccines, post-marketing evaluation of these vaccines is still required to assess their efficacy and safety in real-world settings. Real-word data may also provide significant assurance to the public to accept vaccines [ 23 ]. Studies in phase 3 trials may have some limitations in evaluating vaccine efficacy and safety as they recruit a small number of participants as well as a healthier than average sample population. This may result in misidentification of less frequent adverse events [ 20 ]. The rapid development of COVID-19 vaccines due to the urgency of the pandemic and the implementation of a newly emerging technique for vaccine development (i.e., mRNA vaccine) have led to some concerns regarding potential side effects [ 24 , 25 , 26 , 27 , 28 ]. Although several reports have been released on the safety and effectiveness of vaccines against SARSCoV-2, real-world data on the safety of this novel messenger RNA (mRNA)-based COVID-19 vaccine, particularly in children, are still scarce. Further, epidemiological studies, despite their known limitations, are important to evaluate the short-term COVID-19 side effects and to reassure the public about vaccine safety and effectiveness, which should not be very different from those reported in the clinical trials. Therefore, this study aimed to investigate short-term side effects after receiving the COVID-19 Pfizer-BioNTech vaccine in children aged 12–18 years in Saudi Arabia.

2. Materials and Methods

2.1. study design, population, and setting.

A retrospective, cross-sectional study was conducted using a self-administered online survey to report side effects in children aged 12–18 years-old following Pfizer-BioNTech (BNT162b2) vaccination in Saudi Arabia. The survey was designed to have a dual language (Arabic and English) questionnaire, using Google Forms, which was delivered to participants via social media between 1st August to 24th August of 2021. This study included participants who received both single and double doses of the Pfizer-BioNTech (BNT162b2) vaccine. The survey was developed after an intensive literature search that included PubMed, Medline, Google Scholar, and other databases, aiming to identify potential and common short-term side effects post-Pfizer-BioNTech (BNT162b2) vaccine. The questionnaire was designed to have multiple sections. The first section has an introductory part about the purpose of the study, contact details for the study investigators to facilitate communication between study investigators and participants as well as a consent section for agreeing to participate in the study. The second section was designed to collect general information about the study participants including gender, age, chronic diseases such as hemoglobinopathies, type 1 diabetes, asthma, and others, as well as previous infection history with SARS-CoV-2 infection. The third section was formulated to focus mainly on the COVID-19 vaccine-related data such as number of doses received, side effects experienced following COVID-19 vaccine, timing, and duration of the side effects. Participants were also allowed to report no symptoms by leaving the box unchecked. We have included a subsection for side effects where we listed the most frequent side effects reported by other studies [ 20 , 29 , 30 , 31 , 32 ], including pain at the sites of injection, fatigue, headache, fever and chills, nausea, and vomiting. Additionally, we also provided a section for reporting other unlisted side effects which might have been experienced by our study participants. Further, we also questioned the participants to report doctors’ visits after vaccination, any admissions to hospitals post-vaccination, or the use of any medications taken post-vaccination.

2.2. Ethical Approval

Ethical approval for conducting this study was obtained from the standing ethical approval committee at Jazan University (reference number; REC42/1/087, date 22 March 2021). Consent was obtained from all participants or their tutors prior to participation in the study. The study excluded responses that did not contain the informed consents, participants who provided incomplete responses, those outside the age group of 12–18 years old, and those who received a COVID-19 vaccine other than the Pfizer-BioNTech (BNT162b2) vaccine.

2.3. Sample Size and Statistical Analysis

The sample size was calculated using raosoft.com. As there were no statistics available for the number of children in this age group among the total Saudi population, we used the whole country population (around 30 million) as our population size. The sample size was calculated based on a 5% margin of error, a 50% response rate, and a 95% confidence interval, for a population of 30 million inhabitants. Consequently, a sample size of 385 responses was determined to be sufficient for this study. However, to reduce sampling bias in our method as this study was based on an online questionnaire distributed via social media, we increased the sample size to include 965 participants, which is more than 2-folds of the required size. Descriptive statistics were reported for the collected data. Further descriptive analysis using t-test and chi-square test were performed for statistical purposes for all participants, and those who are presented with side effects versus those without side effects. Then, further descriptive analysis using t-test and chi-square test were done for those who received single dose versus two doses. The data were statistically analyzed using SPSS v.23 (IBM Corp., Armonk, NY, USA) with a significance level of p = 0.05 value.

3.1. Characteristics of the Study Participants

A total of 965 responses were included in our study, while 50 participants were excluded from the analysis as they provided incomplete responses (i.e., providing inconsistent or incomplete responses, missing important items such as informed consent, age, number of doses, etc.). The median age for the study participants was 16 years old with almost 48% of the participants being male. Only 29% of the study participants reported that they had been previously diagnosed with COVID-19. A total of 10% of our study participants reported that they have current health conditions such as type 1 diabetes, sickle cell anemia, and asthma, while 44% of the participants reported that they had received two doses of the vaccines. Overall, almost 60% of the study participants experienced side effects. These data are also summarized in Table 2 . We further categorized our study participants into two main groups, i.e., participants who experienced side effects and those who did not experience any side effects after vaccination. The two groups were then compared against each other using several parameters including age, sex, presence of health diseases, previous infections with SARS-CoV-2, and the number of doses received ( Table 3 ). There was a significant association between the presence of post-vaccination side effects and the number of received doses ( p = 0.003) ( Table 3 ). Furthermore, significantly more side effects were reported among individuals with history of previous diagnosis of SARS-CoV2 ( Table 3 ).

General characteristics of study participants.

a Median ± SD (SD: Standard Deviation).

Univariate analysis of the participants who presented with side effects compared to those without side effects following COVID-19 vaccination.

SD: Standard Deviation. # The alpha criterion for p -value was set to 0.05. * Significant in univariate analysis.

3.2. Side Effects Following Vaccinations

In the present study, 571 of the study participants reported side effects following vaccination, representing 60% of the total study subjects ( Table 2 ). The most frequently reported side effects among those who reported side effects after vaccination were pain or redness at the site of injection (90%), fatigue (67%), fever (59%), headache (55%), nausea or vomiting (21%), and chest pain and shortness of breath (20%). Joint or bone pain were reported less frequently among our participants (2%) ( Figure 1 ). Almost 20% of the participants reported that the side effects started on the 2nd day following vaccination, while only 8% noticed similar side effects starting at day 3 or later post-vaccination ( Table 4 ). These side effects lasted for 1–3 days in 65% of the participants, 3–5 days in 30% of the study subjects, and only 5% of them reported prolonged side effects, extending for more than 5 days following vaccination ( Table 4 ). 65% of the participants reported taking painkillers to relieve the vaccine effects, with few participants needing to visit physicians or requiring hospitalization, at 14% and 8%, respectively ( Table 4 ). Additionally, none of those who experienced side effects after vaccination reported side effects that were not listed in the questionnaire. Overall, these data indicate that more than half of the study participants who received Pfizer-BioNTech (BNT162b2) vaccine reported at least one side effect. However, these side effects were short-term in the majority of participants.

Comparison of side effects after either one or two doses of the Pfizer-BioNTech (BNT162b2) vaccine in the study participants.

General characteristics of the participants presented with side effects after COVID-19 vaccination.

SD: Standard Deviation.

3.3. Comparison of Side Effects Reported Following One- or Two-Dose Vaccinations

We further categorized the participants who reported side effects following vaccination into 2 groups, i.e., participants who received single doses and participants who received two doses of Pfizer-BioNTech (BNT162b2) vaccine. These two groups were compared against each other using several parameters, including previous history of infection with SARS-CoV-2, presence of chronic health conditions, gender, time and duration of side effects, and the types of side effects experienced following vaccination ( Table 5 ). Our data showed that side effects were commonly reported in participants who received two doses compared to the singly dosed participants. In particular, fatigue, fever, chills, headache, vomiting were the most frequently reported side effects among participants with two doses ( Table 5 ). More participants in the two doses groups tended to take medication and were admitted to hospitals compared to singly dosed individuals, with 74% vs. 56% and 12% vs. 5%, respectively ( Table 5 and Figure 1 ). Lastly, as shown in Table 2 , reports of side effects are significantly associated with previous SARS-CoV-2 infection; here, we show that the more frequent side effects reported after the second dose compared to the first dose were neither associated with the presence of health issues nor with previous SARS-CoV-2 infection. Taken together, this data shows clearly that more significant side effects are reported after the second dose of Pfizer-BioNTech (BNT162b2) vaccine compared to the first dose in our study cohort.

Comparison of side effects after one or two doses of the Pfizer-BioNTech (BNT162b2) vaccine.

4. Discussion

Vaccines have been proven to play critical roles in eliminating and controlling infectious diseases’ epidemics. The rapid development and availability of COVID-19 vaccines have brought a glimmer of hope to the world, and it is believed that widespread vaccination seems to be the most effective method of controlling the ongoing COVID-19 pandemic. However, vaccine acceptance and uptake could influence the efforts to control the spread of the COVID-19 pandemic. Given the rapid development and emergency authorization of COVID-19 vaccines, more trepidation about receiving COVID-19 vaccines were noticed among some populations worldwide. Furthermore, the recent reports of some rare cases of serious side effects such as thrombosis [ 33 ] and myocarditis [ 34 , 35 ] following COVID-19 vaccines may affect the acceptance of COVID-19 vaccines among some populations. Therefore, continuous monitoring of COVID-19 vaccines is essential to enhance the reassurance and acceptance of COVID-19 vaccines among the public. In contribution to this, we have conducted a cross-sectional, observational study to analyze the short-term adverse events following administration of Pfizer/BioNTech (BNT162b2) COVID-19 vaccines in children aged 12–18 years in Saudi Arabia.

Saudi Arabia is one of first countries that approved COVID-19 vaccines in children 12 years old and older immediately following the release of sufficient data on vaccine safety and efficacy in this age group [ 15 , 16 ]. In an effort to reach herd immunity as quickly as possible and to prevent SARS-CoV-2 infection in schools and universities, Saudi Arabia has made it mandatory for all persons 12 years and above to receive two doses of COVID-19 vaccines. In this web-based study, we aimed to investigate the adverse effects following administration of COVID-19 Pfizer/BioNTech (BNT162b2) vaccines in children between the age of 12–18 years old in Saudi Arabia. We found that systemic adverse effects were reported in almost 60% of our study participants. In a prior study investigating the short-term side effects of Pfizer/BioNTech in participants aged 18 to 70 years old, we have observed fewer overall report of side effects (40%, n = 208) [ 36 ]. More side effects have been reported by the younger population compared to their older counterparts [ 37 , 38 ]. This observation may be explained by the stronger and more efficient immune systems of younger people compared to older age group [ 19 , 39 ]. Pain/redness at the injection site (90%), fatigue (67%), fever (48%), and headache (55%) were the most frequently reported side effects by the study participants ( Figure 1 ). The data from the present study are in support of the data from clinical trials as well as other real-world studies [ 20 , 21 , 22 , 23 , 24 ]. For example, in phase 3 clinical trials of the BNT162b2 vaccine, the three most common events after the first dose were injection-site pain (71–83%), fatigue (34–47%), and headache (25–42%) [ 21 ]. We also found that only 14% of the participants needed to see a doctor due to vaccine side effects, and only 8% of individuals were admitted to the hospital following vaccination. While the reported side effects were commonly associated with the COVID-19 vaccine, physician visits and hospitalizations after vaccination in this age group could be driven by more worrisome parents about their children.

Published literature showed that side effects were more prevalent in females than in males and in people aged 55 years or younger than in those older than 55 years [ 22 , 23 , 24 ]. Similarly, our data also showed that in children between 12–18 years, female participants reported more side effects than males. The variation in immunogenicity towards vaccinations is believed to be related to the biological differences which are imposed by gender differences [ 35 ]. Notably, a significant association between the presence of side effects and the number of received doses was also observed in the current study. More importantly, more side effects were reported in individuals with previous exposure to SARS-CoV-2 compared to those with no history of infection ( Table 3 ). Both of these data agree with several prior reports which showed that more side effects were reported following the second doses as well as in people with a history of COVID-19 [ 20 , 21 , 22 , 23 , 38 ]. This observation could be interpreted on the basis of the immune system’s response. For instance, emerging real-world evidence indicates that the humoral immunity in individuals with prior SARS-CoV-2 infection following a single dose of the vaccine is equal to or stronger than what is found in SARS-CoV-2-naïve individuals following the second doses [ 40 ]. Such improved immunity may induce the production of cytokines that may have an inflammatory effect on muscles, blood vessels, and other tissues, mediating more systemic adverse effects post second doses or following doses in individuals who had previously been infected with SARS-CoV 2 [ 41 ]. Although it remains to be tested, this increased reactogenicity may indicate increased immunogenicity and vaccine effectiveness. However, as our work in this study is observational, we cannot directly comment on the effectiveness of the given vaccine.

To the best of our knowledge, this is the first study to investigate the adverse effects of the Pfizer-BioNTech vaccine in children aged 12–18 years old in Saudi Arabia. We have shown that the current study participants reported only common side effects which were previously reported in several other studies. Notably, we have provided our study participants with a choice to report any other side effects which were not listed in the survey. However, no other adverse effects were reported by any of the study participants, indicating that our data is in strong agreement with the type of adverse effects that were reported from phase 3 clinical study.

The data from our study showed that side effects were more frequently reported after the second doses and among individuals with a history of previous exposure to SARS-CoV-2. Results from our study may contribute to increasing the public confidence in the safety profile of COVID-19 Pfizer/BioNTech vaccines, which may contribute to accelerating the process of vaccination coverage. Our study still bears some limitations. First, the study used self-reported data, which may introduce information bias, such as inconsistency in participants’ reports, i.e., some participants might be more likely to report adverse effects than others. Additionally, the distribution of this survey was dependent on the authors’ networks. A community-based survey would be more appropriate for this kind of study. However, since social distancing is still strongly recommended, we preferred to conduct this study as a web-based study to ensure the safety of all our study participants. Another limitation of the current study is that it monitored the vaccine’s short-term side effects (immediately after injection). The medium and long-term effects of the vaccine are still unknown in our study cohort. It would be of importance for future study to assess other rare events following COVID-19 vaccination such as thromboembolic profiles and myocarditis [ 34 ].

5. Conclusions

In conclusion, the side effects following the COVID-19 Pfizer-BioNTech vaccine in children aged 12–18 years are common side effects which were previously reported in several other studies and do not persist for long. The adverse effects were more frequently reported among those who previously had COVID-19 and following the second doses. Data from our study may contribute to increasing public confidence regarding side effects associated with COVID-19 Pfizer/BioNTech vaccines, which may contribute to accelerating the process of vaccination coverage. A follow-up study on a larger population to evaluate the long-term side effects as well the effectiveness of the COVID-19 vaccines in children is warranted.

Acknowledgments

We would like to thank the Medical Research Center (MRC) and the University Hospital at Jazan University for their continuous support. We are also immensely thankful to the participants of this study.

Author Contributions

Conceptualization, E.A., A.A. (Abdulaziz Alhazmi) and A.A. (Abdullah Algaissi); methodology, A.A. (Abdulaziz Alhazmi) and E.A.; validation, A.A. (Abdulaziz Alhazmi), A.A. (Abdullah Algaissi), M.Q. and E.A.; formal analysis, A.A. (Abdulaziz Alhazmi) and E.A.; investigation, A.A. (Abdullah Algaissi), A.A. (Abdulaziz Alhazmi), E.A., N.A.Q., R.A., G.G., H.A. and M.Q.; resources, A.A. (Abdulaziz Alhazmi), A.A. (Abdullah Algaissi), E.A. and A.M.H.; data curation, R.A., A.A. (Abdulaziz Alhazmi), N.A.Q. and E.A.; writing—original draft preparation, E.A. and A.A. (Abdullah Algaissi); writing—review and editing, E.A., A.A. (Abdulaziz Alhazmi), A.A. (Abdullah Algaissi) and A.M.H.; visualization, A.A. (Abdulaziz Alhazmi), A.A. (Abdullah Algaissi) and E.A.; supervision, A.A. (Abdulaziz Alhazmi), A.A. (Abdullah Algaissi) and E.A.; project administration, A.A. (Abdulaziz Alhazmi); funding acquisition, A.A. (Abdulaziz Alhazmi). All authors have read and agreed to the published version of the manuscript.

This research was funded by the Deanship of Scientific Research, Jazan University, Jazan, Saudi Arabia (Project number: Cov19-56). The authors therefore acknowledge with thanks Deanship of Scientific Research at Jazan University for financial and technical support.

Institutional Review Board Statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Research Ethics Committee of Jazan University, Saudi Arabia (IRB Approval number REC42/1/001, approved date 19 August 2020).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

Conflicts of interest.

The authors declare no conflict of interest.

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