cdc.gov/coronavirus

Pfizer-BioNTech COVID-19 

Vaccine Booster: 

Benefits-Risk Discussion

Megan Wallace, DrPH, MPH

ACIP Meeting

September 23, 2021
Benefits and risks of Pfizer-BioNTech COVID-19 vaccine 

booster dose

2

Benefits of PfizerBioNTech COVID-19 

booster dose

Risks after PfizerBioNTech COVID-19 

booster dose
Benefits-Risk Analysis for Pfizer-BioNTech 

COVID-19 Booster Dose
4

Methods for assessment of benefit-risk balance

Benefits — Calculated per 1 million booster doses (Pfizer-BioNTech)

• Age groups: 18 – 29 years, 30 – 49 years, 50 – 64 years, ≥65 years

• Time Horizon: 180-day period

Input Source

Case Incidence CDC Data Tracker (Sept 9, 2021)1

Hospitalization Incidence COVID-NET (Aug 21, 2021)2

Vaccine Effectiveness (primary series) Averaged VE estimates from four platforms

Vaccine Effectiveness booster Assumption (VE post-booster is unknown)

95% VE for hospitalization

90% VE for infection

VE: Vaccine Effectiveness

1https://covid.cdc.gov/covid-data-tracker/#trends_dailycases

2https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html
5

Current age-specific VE estimates for hospitalization

VE = vaccine effectiveness;

1https://www.medrxiv.org/content/10.1101/2021.08.27.21262356v1

2https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e1.htm?s_cid=mm7037e1_w

3https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e2.htm. Using Pfizer specific estimate.

4https://www.cdc.gov/mmwr/volumes/70/wr/mm7034e2.htm

VE for hospitalization

Age Group COVID-NET, 

April – August 

20211

Scobie et al., 

June – July 

20212

VISION, June 

– August 

20213

IVY Network, 

July – August 

20214

Average VE 

for base case

18 – 29 years 94.7% 93% 85%

90%

90.7%

30 – 49 years 95.6% 93% 82% 90.2%

50 – 64 years 95.5% 91% 84% 94% 91.1%

≥65 years 95.2% 87% 73% 85% 85.1%
6

Methods for assessment of benefit-risk balance

 Harms — per 1 million booster doses (Pfizer-BioNTech)

Input Source

Myocarditis incidence following a 

booster dose

Assumption (myocarditis risk after 3rd dose is unknown) 

Based on Vaccine Adverse Event Reporting System data post dose 2
7

Reporting rates of myocarditis following Pfizer-BioNTech 

vaccination (per million doses administered) by age and dose 

number, 7-day risk period1

All Males Females

Age group Dose 1 Dose 2 Dose 1 Dose 2 Dose 1 Dose 2

18-29 years 

old 1.1 12.9 2.1 24.1 0.2 2.0

30-49 years 

old 0.6 3.1 0.9 5.6 0.4 1.4

50-64 years 

old 0.2 0.5 0.2 0.5 0.3 0.8

≥65 years old 0.2 0.3 0.2 0.4 0.2 0.4

1Data as of August 18, 2021. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-30/03-COVID-Su-508.pdf
Sensitivity analysis performed to account for uncertainty

8

 Varied estimates for how much a booster dose would increase VE

 Varied estimates for what VE is currently

– Modeled increased VE waning by decreasing current VE estimates by 5% intervals

 Modeled variable risk by considering myocarditis incidence seen after dose 2, and 2x dose 2
Benefits vs risks of COVID-19 booster dose

Framework for booster dose benefit-risk analysis

Differential benefits of booster by age groups

Differential benefits of booster compared with primary series

9
114

298

488

2000 1500 1000 500 0

10

13

3

1

0

0 500 1000 1500 2000

Benefits and risks after Pfizer-BioNTech COVID-19 booster dose

18-29

30-49

50-64

≥65

Age groups 

(years)

Cases of Myocarditis

Expected per Million Doses

COVID-19-Associated Hospitalizations

Prevented per Million Doses

Scenario:

• VE for hospitalization averaged from four platforms

• Boost to 95% VE for hospitalization

• Myocarditis risk equivalent to after 2nd dose

2080

. 

Age Group VE for 

hospitalization

18 – 29 years 90.7%

30 – 49 years 90.2%

50 – 64 years 91.1%

≥65 years 85.1%

For every million doses of vaccine given 
114

298

488

2000 1500 1000 500 0

11

26

6

1

1

0 500 1000 1500 2000

Benefits and risks after Pfizer-BioNTech COVID-19 booster dose

18-29

30-49

50-64

≥65

Age groups

(years)

Scenario:

• VE for hospitalization averaged from four platforms

• Boost to 95% VE for hospitalization

• Myocarditis risk equivalent to 2x risk of 2nd dose

2080

. 

Age Group VE for 

hospitalization

18 – 29 years 90.7%

30 – 49 years 90.2%

50 – 64 years 91.1%

≥65 years 85.1%

For every million doses of vaccine given 

Cases of Myocarditis

Expected per Million Doses

COVID-19-Associated Hospitalizations

Prevented per Million Doses
114

298

488

2000 1500 1000 500 0

12

26

6

1

1

0 500 1000 1500 2000

Benefits and risks after Pfizer-BioNTech COVID-19 booster

18-29

30-49

50-64

65+

Age groups

(years)

Scenario:

• VE for hospitalization averaged from four platforms

• Boost to 95% VE for hospitalization

• Myocarditis risk equivalent to 2x risk of 2nd dose

2080

. 

Age Group VE for 

hospitalization

18 – 29 years 90.7%

30 – 49 years 90.2%

50 – 64 years 91.1%

≥65 years 85.1%

For every million doses of vaccine given 

Females: 4 cases of myocarditis

Males: 48 cases of myocarditis

True risk of myocarditis after a 3rd dose unknown

Risk may not be evenly distributed by sex

Cases of Myocarditis

Expected per Million Doses

COVID-19-Associated Hospitalizations

Prevented per Million Doses
13

Cases of Myocarditis Among Males & 

Females Expected per Million Doses

COVID-19-Associated Hospitalizations Among 

Males & Females Prevented per Million Doses

0

100

190

271

0

173

333

480

500 400 300 200 100 0

Benefits and risks after Pfizer-BioNTech COVID-19 booster for 

persons aged 18 – 29 years with varying pre-booster VE, by sex

95%

90%

85%

80%

For every million doses of vaccine given

Scenario:

• Hypothetical, varied pre-booster VE for hospitalization

• COVID-19 hospitalization rates stratified by sex

• Boost to 95% VE for hospitalization

• Myocarditis risk equivalent to risk after 2nd dose, by sex

• Range: risk in 25–29-year-olds – risk in 18–24-year-olds 

1https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e1.htm?s_cid=mm7037e1_w. 

Pre-Booster 

VE

0 100 200 300 400 500

24

24

24

24

2

2

2

2
14

0

33

63

90

0

58

111

160

500 400 300 200 100 0

Benefits and risks after Pfizer-BioNTech COVID-19 booster for 

persons aged 18 – 29 years with varying pre-booster VE, by sex

95%

90%

85%

80%

For every million doses of vaccine given

Scenario:

• Hypothetical, varied pre-booster VEs

• Hospitalization rates stratified by sex

• Boost to 95% VE for hospitalization

• Myocarditis risk equivalent to risk 2nd dose

• Range: risk in 25–29-year-olds – risk in 18 – 25-year-olds 

• Decreased hospitalization rate to 1/3 of current rate, similar to rates seen in June/July 2021

1https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e1.htm?s_cid=mm7037e1_w. 

Pre-Booster 

VE

0 100 200 300 400 500

24

24

24

24

2

2

2

2

Cases of Myocarditis Among Males & 

Females Expected per Million Doses

COVID-19-Associated Hospitalizations Among 

Males & Females Prevented per Million Doses
26

6

1

1

0 2000 4000 6000 8000 10000 1200015

Cases of Myocarditis Expected per 

Million Doses

COVID-19-Associated Hospitalizations & 

COVID-19 Cases Prevented per Million Doses

114

298

488

2080

9500

10000

7500

8000

12000 10000 8000 6000 4000 2000 0

Benefits and risks after Pfizer-BioNTech COVID-19 booster

18-29

30-49

50-64

65+

For every million doses of vaccine given

Scenario:

• VE for hospitalization averaged from four platforms

• VE for infection estimates from Scobie et al.1

• Boost to 95% VE for hospitalization, 90% VE for infection

• Myocarditis risk equivalent to 2x risk of 2nd dose

1https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e1.htm?s_cid=mm7037e1_w. 

Age Group VE for 

hospitalization

VE for infection

18 – 29 years 90.9% 78%

30 – 49 years 90.2% 78%

50 – 64 years 90.2% 80%

≥65 years 85.1% 78%

Age groups

(years)
Benefits and risks after Pfizer-BioNTech COVID-19 booster in 

persons aged 18-29 years and 65+ years

16

Age Group VE for 

hospitalization

18 – 29 years 90.7%

≥65 years 85.1%

85 90 9595 100

2,000

0

2,500

3,000

Booster effectiveness against hospitalization

Change in risk of hospitalization (per million)

1,500

1,000

500

Benefit: reduction in COVID hospitalization, 18-29

Harm: increase in myocarditis hospitalization, 18-29

Benefit: reduction in COVID hospitalization, 65+

Harm: increase in myocarditis hospitalization, 65+

Variation by booster effectiveness against hospitalization
Number needed to vaccinate with booster dose to prevent one 

hospitalization over 6 months

17

8738

3361

2051

481

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

18-29 30-49 50-64 65+

Number needed to vaccinate to prevent 

one hospitalization

Age groups (years)
Number needed to vaccinate with booster dose to prevent one 

hospitalization or infection over 6 months

18

8738

3361

2051

481

105 97 134 125

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

18-29 30-49 50-64 65+

Number needed to vaccinate to prevent 

one hospitalization or infection

Age groups (years)

Hospitalizations

Infections
19

Relative benefits of booster dose vs primary series vaccination with 

Pfizer-BioNTech COVID-19 Vaccine

Scenario:

• VE for hospitalization averaged from four platforms

• VE for infection estimates from Scobie et al.1

• Boost to 95% VE for hospitalization and 90% VE for infection

• Primary series assumes 1,000,000 doses used to provide 500,000 primary series

• Primary series provides 95% VE for hospitalization and 90% VE for infection

• Presented as number needed to vaccinate

1https://www.cdc.gov/mmwr/volumes/70/wr/mm7037e1.htm?s_cid=mm7037e1_w. 
Number needed to vaccinate to prevent one hospitalization

over 6 months, booster versus primary series

20

8738

3361

2051

396 481 170 84 50

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

18-29 30-49 50-64 65+

Number needed to vaccinate to prevent 

one hospitalization

Age groups (years)

Booster

Primary Series 22x 

higher

10x 

higher
 Benefit-risk analyses very sensitive to pre-booster vaccine effectiveness 

and effectiveness data for Delta variant are limited

– Available age specific U.S. data based on month of COVID-19 onset, not on duration 

since vaccination 

– Preferred pre-booster data would measure effectiveness by duration since 2nd dose 

(e.g., 6 months, 8 months)

 Post-booster effectiveness and post-booster myocarditis risk are 

unknown and based on available evidence from the primary series

 Model assumes static incidence and VE over a 6-month period

Limitations

21
 Direct benefit-risk assessment for Pfizer-BioNTech COVID-19 vaccine booster & 

myocarditis

– Considers individual benefits of vaccination vs. individual risks

 Using current VE estimates, benefit/risk balance most favorable for adults ≥65 years of 

age

– Current estimates show smaller benefits for population <65 years of age 

 Benefits increase in scenarios with lower VE for prevention of hospitalization and cases

 Risks of myocarditis after a 3rd dose of mRNA vaccines may vary by age and sex

– Highest rates of myocarditis after the 2nd dose seen in younger males

22

Summary of benefit-risk balance for Pfizer-BioNTech COVID-19 

booster and myocarditis
Benefits and risks of Pfizer-BioNTech COVID-19 Vaccine

booster dose by age 

23

Benefits

of providing a 

Pfizer-BioNTech 

COVID-19 

booster dose

Risks

of providing a 

Pfizer-BioNTech 

COVID-19 

booster dose

Prevention of COVID-19 cases, 

hospitalizations and deaths

Possible prevention of 

transmission

Myocarditis or other rare events 

after mRNA vaccines

Short-term reactogenicity
 Danielle Moulia

 Stephen Hadler

 Kathleen Dooling

 Sara Oliver

 Julia Gargano

 Heidi Moline

 Jennifer Collins

 Jefferson Jones

 Eddie Shanley

 Monica Godfrey

 Kevin Chatham-Stevens

 Stephanie Bialek

 Ruth Link-Gelles

 Amanda Cohn

 Tom Shimabukuro

 John Su

 Fiona Havers

 Christopher Taylor

 Florence Lee

 Carla Black

 Linda Mattocks

 Heather Scobie

 Ben Silk

 Amitabh Suthar

 Mark Tenforde

 Mark Thompson

Acknowledgements

24

 COVID-NET Team

 DAV Vaccine Team

 Vaccine Safety Team

 Epidemiology and Surveillance Task Force

 Vaccine Task Force
For more information, contact CDC

1-800-CDC-INFO (232-4636)

TTY: 1-888-232-6348 www.cdc.gov

The findings and conclusions in this report are those of the authors and do not necessarily represent the 

official position of the Centers for Disease Control and Prevention.

Thank you