Centers for Disease Control and Prevention

National Center for Immunization and Respiratory Diseases

Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.

Benefit and risk assessment for COVID-19 vaccines

Megan Wallace, DrPH, MPH
Benefit-risk assessment 

2

 Benefits of COVID-19 vaccine by age for primary series 

 Incremental benefits of COVID-19 vaccine by age and time since last dose for 

bivalent booster dose

– Sensitivity analyses model high and low points in the pandemic

 Benefit-risk assessment for bivalent booster dose

– Focused on ages 12-17 years and 18-49 years
Methods for benefit assessment

3

Benefits – Calculated per 1 million primary series or bivalent booster doses

 Hospitalization rates1: December 2022 COVID-19-associated hospitalization rate among persons 

aged 5–11, 12–17, 18–49, 50–65, 65+ years, by vaccination status, from COVID-NET

– Sensitivity analyses model high and low points in the pandemic

 Time horizon2: 6 months

 Vaccine Effectiveness: VE estimates from VISION3 with assumption of waning of effectiveness 

by 10% each month starting after month 2

– VE of primary series based on absolute VE for bivalent dose4

– VE of bivalent booster dose based on relative VE by interval from last monovalent dose to 

bivalent5

1https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination. Rates among unvaccinated used for primary series assessment. Rates among those vaccinated with 

monovalent doses only used for bivalent booster dose assessment. 

2Period over which benefits of bivalent vaccination accrue 

3https://www.cdc.gov/mmwr/volumes/71/wr/mm715152e1.htm?s_cid=mm715152e1_w. 

4Absolute VE of bivalent booster dose (57%) used as the estimated primary series VE. Absolute VE from the bivalent booster was used as an estimate of primary series VE because current VE of 

monovalent primary series is unknown. 

5Relative VE of bivalent booster dose used in booster dose assessment (5-7 month interval: 38%; 8-10 month interval: 42%; 11+ month interval 45%). Relative VE for ED/UC visit was used for 2-4 

month interval (31%) because VE against hospitalization was not available 
Monthly age-adjusted rates of COVID-19-associated hospitalization 

by vaccination status in patients ≥ 18 years, COVID-NET

https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination

4

Age group Rate per 100,000 

persons

5-11 Years 2.13

12-17 Years 2.66

18-49 Years 12.89

50-64 Years 27.48

≥ 65 Years 121.10

December 2022 hospitalization rates per 

100,000 vaccinated persons with no 

bivalent booster by age group, COVID-NET
Estimated COVID-19-associated hospitalizations prevented over 6 

months for every million mRNA COVID-19 primary series given 

248

944

2465

5033

15978

0 2000 4000 6000 8000 10000 12000 14000 16000 18000

COVID-19-associated hospitalizations prevented over 6 months per million doses by age group

Based on hospitalization rates from December 2022

12 – 17 years

18 – 49 years

50 – 64 years

≥ 65 years

5

5 – 11 years
Estimated COVID-19 hospitalizations prevented over 6 months for 

every million mRNA COVID-19 primary series and bivalent booster doses1

53

257

549

2419

944

2465

5033

15978

0 2000 4000 6000 8000 10000 12000 14000 16000 18000

COVID-19-associated hospitalizations prevented over 6 months per million

primary series or bivalent booster by age group

Based on hospitalization rates from December 2022

12 – 17 years

18 – 49 years

50 – 64 years

≥ 65 years

1. Calculated assuming booster dose given ≥11 months from last monovalent vaccine dose 6
Estimated COVID-19 hospitalizations prevented over 6 months for 

every million bivalent mRNA COVID-19 booster doses, by age group and 

dose interval1

0 500 1000 1500 2000 2500 3000

COVID-19-associated hospitalizations prevented over 6 months per million doses given in 

2 – 4 month interval, 5 – 7 month interval, 8 – 10 month interval, ≥11 month interval

Based on hospitalization rates from December 2022

12 – 17 years

18 – 49 years

50 – 64 years

≥ 65 years

1Interval refers to the time between the most recent monovalent dose and a bivalent dose. 7
Monthly age-adjusted rates of COVID-19-associated hospitalization 

by vaccination status in patients 12 – 17 years, COVID-NET

https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination

High

Low Recent

8
Estimated COVID-19 hospitalizations prevented over 6 months for 

every million bivalent mRNA COVID-19 booster doses, 12 – 17-year-olds

0 20 40 60 80 100 120 140 160

COVID-19-associated hospitalizations prevented over 6 months per million

doses by low, recent, and high incidence1

2-5 month interval2

5-7 month interval2

8-10 month interval2

11+ month interval2

9

1Low incidence scenario uses hospitalization rate from March 2022, recent incidence scenario uses hospitalization rate from December 2022, and high incidence 

scenario uses hospitalization rate from July 2022

2Interval refers to the time between the most recent monovalent dose and a bivalent dose. 
Dosing intervals for monovalent booster and bivalent 

booster, by age group 

IZ Data Lake: Accessed 2/7/2023

0% 20% 40% 60% 80% 100%

12-17 year olds

18-49 year olds

2-4 month interval 5-7 month interval

8-10 month interval 11+ month interval

0% 20% 40% 60% 80% 100%

12-17 year olds

18-49 year olds

2-4 month interval 5-7 month interval

8-10 month interval 11+ month interval

Interval between completion of the primary series 

and monovalent booster

Interval between completion of the most recent 

monovalent dose* and bivalent booster

* Primary series or monovalent booster

 Among adolescents who received a monovalent booster, nearly half received the 

monovalent booster at an interval <8 months after their primary series 

 Over 90% of adolescents received a bivalent booster ≥8 months after their previous dose
 Limited data to inform myocarditis risk after bivalent COVID-19 vaccine booster dose 

–

–

–

Preliminary VSD myocarditis rates following bivalent booster dose in adolescent and young adult 

males lower than first monovalent boosters, but limited by small numbers of doses administered

 Myocarditis risk lower with longer time between doses 

Rates of myocarditis lower with extended interval between dose 1 and dose 2 for primary series1

Longer interval between doses for bivalent boosters, compared to monovalent boosters, may 

also impact myocarditis rates

 Most individuals with myocarditis/pericarditis have fully recovered at follow-up2

 The risk of adverse cardiac outcomes were 1.8 – 5.6 times higher after SARS-CoV-2 

infection than after mRNA COVID-19 vaccination among males ages 12-17 years3

Myocarditis and COVID-19 vaccines

11

1 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/11-COVID-Moulia-508.pdf 2https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/04-COVID-Kracalic508.pdf 3https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm?s_cid=mm7114e1_w
VSD incidence rates of verified myocarditis or pericarditis in the 0-7 days 

after Pfizer-BioNTech vaccination in people 12 – 39 years1

1 Primary series and 1st monovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; Source: Kristin Goddard, Kayla E. Hanson, Ned Lewis, 

et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID-19 Vaccination Among Children and Younger Adults in the United States. Ann Intern Med. [Epub 4 October 

2022]. doi:10.7326/M22-2274

Dose 2 Primary Series 

Pfizer-BioNTech

1st Monovalent Booster Dose 

Pfizer-BioNTech

Bivalent Booster Dose

Pfizer-BioNTech

Age & Sex Cases Dose 2 

Total

Incidence rate/ 

million doses 

(95% CI)

Cases 1st Booster 

Total

Incidence rate/ 

million doses 

(95% CI)

Cases Bivalent 

Booster Total

Incidence rate/ 

million doses

(95% CI)

12-17 Years

Males

Females

45

6

308,046

311,247

146.1 (106.6 – 195.5)

19.3 (7.1 – 42.0)

14

2

129,487

139,118

108.1 (59.1 – 181.4)

14.4 (1.7 – 51.9)

0

0

48,066

49,725

0.0 (0.0 – 62.3)

0.0 (0.0 – 60.2)

18-29 Years

Males

Females 27

2

331,889

400,321

81.4 (53.6 – 118.4)

5.0 (0.6 – 18.0)

7

1

166,973

240,226

41.9 (16.9 – 86.4)

4.2 (0.1 – 23.2)

1

0

50,687

80,211

19.7 (0.5 – 53.1)

0.0 (0.0 – 37.3)

30-39 Years

Males

Females 5

3

341,527

410,713

14.6 (4.8 – 34.2)

7.3 (1.5 – 21.3)

3

1

197,554

268,412

15.2 (3.1 – 44.4)

3.7 (0.1 – 20.8)

0

0

82,191

115,014

0.0 (0.0 – 36.4)

0.0 (0.0 – 26.0)

12
VSD incidence rates of verified myocarditis or pericarditis in the 0–7 days 

after Moderna vaccination in people ages 18–39 years1

1 Primary series and 1st monovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; source: Goddard K, et al. Incidence of Myocarditis/Pericarditis 

Following mRNA COVID-19 Vaccination Among Children and Younger Adults in the United States. Ann Intern Med. 2022;175:1169-1771.

Dose 2 primary series 

Moderna

1st monovalent booster dose 

Moderna

Bivalent booster dose

Moderna

Age/sex Cases Dose 2

total

Incidence rate/

million doses

(95% CI)

Cases 1st booster

total

Incidence rate/

million doses

(95% CI)

Cases

Bivalent

booster

total

Incidence rate/

million doses

(95% CI)

18–29 years

Males

Females 19

0

195,809

243,560

97.0 (58.4 – 151.5)

0.0 (0.0 – 12.3)

7

1

109,337

156,707

64.0 (25.7 – 131.9)

6.4 (0.2 – 35.6)

0

0

18,499

29,561

0.0 (0.0–161.9)

0.0 (0.0–101.3)

30–39 years

Males

Females 8

1

216,583

259,780

36.9 (15.9 – 72.8)

3.9 (0.1 – 21.4)

1

2

149,468

191,765

6.7 (0.2 – 37.3)

10.4 (1.3 – 37.7)

0

0

35,318

47,620

0.0 (0.0–84.8)

0.0 (0.0–62.9)
31 – 136 hospitalizations prevented

9 – 40 ICU admissions prevented

0 – 1 death prevented

Estimated COVID-19 hospitalizations prevented vs. potential myocarditis 

cases for every million bivalent mRNA COVID-19 booster doses: 

12 – 17-year-olds

Per million doses in 12 – 17-year-olds over 6 months1

14

0 myocarditis2 cases in 48,066 males with a bivalent booster 

0 myocarditis2 cases in 49,725 females with a bivalent booster 

1Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8

2Based on preliminary Pfizer-BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0-62) in males and 0 (95% CI: 0-60) in females 
17 – 75 hospitalizations prevented

5 – 22 ICU admissions prevented

0 – 1 death prevented

Estimated COVID-19 hospitalizations prevented vs. potential myocarditis cases for 

every million bivalent mRNA COVID-19 booster doses: 12 – 17-year-olds 

Accounting for potential incidental SARS-CoV-2 infections among hospitalized patients1

Per million doses in 12 – 17-year-olds over 6 months2

15

0 myocarditis3 cases in 48,066 males with a bivalent booster 

0 myocarditis3 cases in 49,725 females with a bivalent booster 

1 Results were adjusted to account for potential incidental findings of SARS-CoV-2 infection by multiplying the estimated hospitalizations, ICU admissions, and deaths prevented by the estimated 

percent of COVID-NET hospitalizations that are likely due to COVID-19 among 12 – 17-year-olds during on Omicron BA.5 predominant period (55%)

2 Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8

3 Based on preliminary Pfizer-BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0-62) in males and 0 (95% CI: 0-60) in females 
117 – 376 hospitalizations prevented

21 – 69 ICU admissions prevented

4 – 11 deaths prevented

Estimated COVID-19 hospitalizations prevented vs. potential myocarditis 

cases for every million bivalent mRNA COVID-19 booster doses: 

18 – 49-year-olds

Per million doses in 18 – 49-year-olds over 6 months1

16

1 myocarditis2 case in 186,695 males with a bivalent booster 

0 myocarditis2 cases in 272,406 females with a bivalent booster 

1Ranges presented for benefits are based on the high and low incidence scenarios presented on slide 7

2Based on preliminary bivalent booster safety data from VSD among persons ages 18-39 years. Among Pfizer-BioNTech recipients, rates per million doses were: 20 (95% CI: 1–53) in males 

ages 18–29 years; 0 (95% CI: 0– 37) in females ages 18–29 years; 0 (95% CI: 0–36) in males ages 30–39 years and 0 (95% CI: 0–26) in females ages 30–39 years. Among Moderna 

recipients, rates per million doses were: 0 (95% CI: 0–162) in males ages 18–29 years; 0 (95% CI: 0– 101) in females ages 18–29 years; 0 (95% CI: 0– 85) in males ages 30–39 years and 

0 (95% CI: 0–63) in females ages 30–39 years. 
81 – 259 hospitalizations prevented

15 – 48 ICU admissions prevented

3 – 8 deaths prevented

Estimated COVID-19 hospitalizations prevented vs. potential myocarditis cases for 

every million bivalent mRNA COVID-19 booster doses: 18 – 49-year-olds

Accounting for potential incidental SARS-CoV-2 infections among hospitalized patients1

Per million doses in 18 – 49-year-olds over 6 months2

17

1 myocarditis3 case in 186,695 males with a bivalent booster 

0 myocarditis3 cases in 272,406 females with a bivalent booster 

1 Results were adjusted to account for potential incidental findings of SARS-CoV-2 infection by multiplying the estimated hospitalizations, ICU admissions, and deaths prevented by the 

estimated percent of COVID-NET hospitalizations that are likely due to COVID-19 among 18 – 49-year-olds during on Omicron BA.5 predominant period (69%)

2 Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8

3Based on preliminary bivalent booster safety data from VSD among persons ages 18-39 years. Among Pfizer-BioNTech recipients, rates per million doses were: 20 (95% CI: 1–53) in males ages 

18–29 years; 0 (95% CI: 0– 37) in females ages 18–29 years; 0 (95% CI: 0–36) in males ages 30–39 years and 0 (95% CI: 0–26) in females ages 30–39 years. Among Moderna recipients, rates 

per million doses were: 0 (95% CI: 0–162) in males ages 18–29 years; 0 (95% CI: 0– 101) in females ages 18–29 years; 0 (95% CI: 0– 85) in males ages 30–39 years and 

0 (95% CI: 0–63) in females ages 30–39 years. 
18

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Benefits of vaccination may continue to accrue beyond time horizon used

Stable hospitalization rates were assumed for the duration of the time horizon

Underlying complexity of vaccine histories and previous infections could not be 

accounted for

COVID-NET hospitalization rates include hospitalizations for which COVID-19 was not a 

primary reason for admission

Current COVID-19 epidemiology, including hospitalization rates used in assessment, 

reflects impact of both prior vaccination and prior infection

– Cannot account for possible future increases in COVID-19 hospitalization rates or new variant

Myocarditis rates following bivalent booster dose are uncertain. Studies are underway 

to assess the long-term impact of vaccine-associated myocarditis

Limitations
 Benefits continue to outweigh risks for primary series vaccination in all age groups

 Benefits of bivalent booster dose vary by age, time since last dose, and COVID-19 incidence

 Risk of myocarditis after COVID-19 vaccines likely reduced by longer interval since last dose

– Additional data can better define risk after bivalent vaccines, but current data encouraging

 Changes in COVID-19 hospitalization rates would impact the benefit assessment

 Additional benefits of COVID-19 vaccines unable to be quantified in benefit-risk assessment

– Likely prevention of post-COVID conditions, possible reduction in transmission, increased confidence 

in social interactions

 Benefit risk assessment will continue to be monitored as new data are available 

 Receipt of primary series continues to be important in all ages 

 Boosters remain an important option to improve protection against severe COVID-19, 

especially for higher-risk populations

19

Summary of benefit-risk balance for bivalent mRNA COVID-19 vaccination
 VEaP Team

–

–

–

–

–

Dani Moulia

Sara Oliver

Evelyn Twentyman

Katherine Fleming-Dutra

Ruth Link-Gelles

 COVID-NET

– Chris Taylor

 ISO

–

–

Eric Weintraub

Tom Shimabukuro

Acknowledgements
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.

Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or

any use by other CDC CIOs or any external audiences.

Thank you