COVID-19 mRNA vaccines in 

adolescents and young adults: 

Benefit-risk discussion 

Dr. Megan Wallace and Dr. Sara Oliver 

ACIP Meeting 

June 23, 2021 

cdc.gov/coronavirus 
Current COVID-19 mRNA vaccine policy 

▪ COVID-19 vaccines are recommended for persons 12 years of 

age and older in the United States under FDA’s Emergency Use 

Authorization 

2 
COVID-19 mRNA vaccines in adolescents and young adults 

Risk after 

COVID-19 mRNA 

vaccines in 

adolescents and 

young adults 

3 
COVID-19 mRNA vaccines in adolescents and young adults 

Risk after 

COVID-19 mRNA 

vaccines in 

adolescents and 

young adults 

Benefits of 

COVID-19 mRNA 

vaccines in 

adolescents and 

young adults 

4 
COVID-19 mRNA vaccines in adolescents and young adults: 

Benefit-risk discussion 

▪ Public health problem 

– COVID-19 infections and complications in adolescents and young adults 

• Epidemiology in adolescents and young adults 12–29 years of age 

– Post-COVID conditions, including MIS-C and MIS-A 

– Myocarditis 

▪ Benefit/Risk assessment 

– Benefits of mRNA vaccines 

– Risk of myocarditis after mRNA vaccines 

▪ Work Group interpretation 

▪ Questions for ACIP 

5 
Public Health Problem
 Jun 5 2021 

Overall COVID-19 cases in the US have been declining since 

January January 22, 2020 – June 15, 2021 

350000 

0 

50000 

100000 

150000 

200000 

250000 

300000 

Number of COVID-19 Cases 

Jan 22 2020 May 1 2020 Aug 9 2020 Nov 17 2020 Feb 25 2021 June 15 2021 

https://covid.cdc.gov/covid-data-tracker/#trends_dailytrendscases 7 
 

Based on projections, cases may increase substantially in the setting 

of low vaccination rates and high variant transmissibility 

High vaccination (83%) 

Low variant transmissibility 

Low vaccination (68%) 

High variant transmissibility 

12/2020 3/2021 7/2021 11/2021 12/2020 3/2021 7/2021 11/2021 

COVID-19 Scenario Modeling Hub Round 5: https://covid19scenariomodelinghub.org/viz.html 8 
 

Variants of concern (VOC) are an increasing proportion of 

SARS-CoV-2 lineages circulating in the US Percent of Viral Lineages

March 13 – June 19, 2021 with NOWCAST 

Variants of Concern 

B.1.1.7 (Alpha) 52% 

P.1 (Gamma) 16% 

B.1.617.2 (Delta) 21% 

B.1.351 (Beta) <1% 

B.1.427/B.1.429 (Epsilon) <1% 

Collection Date, 2-weeks ending 

CDC COVID Data Tracker As of 6/14/21; VOC=Variant of Concern; VOI=Variant of Interest 9 
 

 

Adolescents and young adults have the highest COVID-19 

incidence rates 

COVID-19 Incidence Rate per 100,000 Population, by Age Group and Sex 

April 1, 2021 – June 11, 2021 

12-17 Years 

18-24 Years 

25-29 Years 

30-49 Years 

50-64 Years 

65+ Years 

COVID-19 Incidence Rate per 100,000 Population 

0.0 200.0 400.0 600.0 800.0 1000.0 1200.0 

Female 

Male 

https://covid.cdc.gov/covid-data-tracker/#demographics 10 
Adolescents and young adults have the highest COVID-19 

incidence rates 

COVID-19 Incidence Rate per 100,000 Population, by Age Group and Sex 

April 1, 2021 – June 11, 2021 

Since beginning of 

pandemic at least 7.7 

million COVID-19 cases 

have been reported 

among persons aged 

12–29 years 

0 200 400 600 800 1000 1200 

12-17 Years 

18-24 Years 

25-29 Years 

30-49 Years 

50-64 Years 

65+ Years 

Female 

Male 

COVID-19 Incidence Rate per 100,000 Population 

 

 

https://covid.cdc.gov/covid-data-tracker/#demographics 11 
 

12%

9%

19%

41%

19%

Adolescents and young adults are an increasing proportion 

of COVID-19 cases reported 

Proportion of Total COVID-19 Cases by Age Group 

- United States, March 1, 2020 – May 31, 2021 

4% 7% 

28% 33% 

25% 

25% 

29% 

25% 

15% 

9% 

0% 

10% 

20% 

30% 

40% 

50% 

60% 

70% 

80% 

90% 

100% 

December 

2020 

May 

2021 

Mar-20 May-20 Jul-20 Sep-20 Nov-20 Jan-21 Mar-21 May-21 

5-11 Years 12-29 Years 30-44 Years 45-64 Years ≥65 years

https://covid.cdc.gov/covid-data-tracker/#demographicsovertime 12

 

As more older adults are 

vaccinated, adolescents & 

young adults make up 

greater % of total cases: 

33% of cases reported in 

May 2021 among persons 

aged 12–29 years 
COVID-19-associated hospitalization rates have remained 

stable in adolescents and young adults 

Weekly COVID-19-associated hospitalization rates, by age group 

Rates per 100,000 population 

9.0 

8.0 

7.0 

6.0 

5.0 

4.0 

3.0 

2.0 

1.0 

0.0 

COVID-NET, March 7, 2020 – May 22, 2021 

25-29 years 

18-24 years 

12-17 years 

https://gis.cdc.gov/grasp/COVIDNet/COVID19_3.html 13 
 

COVID-19-associated deaths continue to occur in 

adolescents and young adults 

COVID-19 Mortality Rate per 100,000 Population, by Age Group and Sex 

April 1, 2021 – June 11, 2021 

12-17 Years 

18-24 Years 

25-29 Years 

COVID-19 Mortality Rate per 100,000 Population 

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 

Female 

Male 

 

 

Since beginning of 

pandemic, 

2,767 COVID-19 deaths 

have been reported 

among persons 

aged 12-29 years; 

316 deaths reported 

since April 1, 2021 

https://covid.cdc.gov/covid-data-tracker/#demographics 14 
 

 

Post-COVID conditions can occur after COVID-19 

▪ No standardized definition, but generally new or persisting symptoms from acute 

infection or exacerbation of a chronic condition ≥4 weeks after SARS-CoV-2 infection 

▪ Reported after infections ranging from asymptomatic to severe 

▪ Limited data in adolescents/young adults, but recent cross-sectional studies have 

shown evidence of new or persisting COVID symptoms in this age group1,2 

– Up to one-half of study participants had symptoms 1 month post-diagnosis 

– Symptoms reported include fatigue, insomnia, rhinorrhea, muscle pain, headache, 

lack of concentration, exercise intolerance, dyspnea, chest pain 

1Buonsenso et al, Acta Paediatrica (2021) 

2Walsh-Messinger et al, medRXiv (2020) 

15 
 

 

 

 

 

 

Multisystem Inflammatory Syndrome in Children (MIS-C) 

▪ Severe hyperinflammatory syndrome occurring 2–6 weeks after acute SARS-CoV-2 

infection among persons <21 years old, resulting in a wide range of manifestations 

and complications 

– 60%–70% of patients are admitted to intensive care, 1%–2% die1,2 

▪ 4,018 MIS-C cases have been reported to national surveillance as of June 2, 20213 

– Estimated incidence of 1 MIS-C case in 3,200 SARS-CoV-2 infections4 

– 36% of cases in persons aged 12–20 years 

– 62% of reported cases have occurred in children who are Hispanic/Latino or Black, 

Non-Hispanic 

1. Feldstein LR, Tenforde MW, Friedman KG, et al. Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) 

Compared With Severe Acute COVID-19. JAMA. 2021;325(11):1074-1087. doi:10.1001/jama.2021.2091 

2. Belay ED, Abrams J, Oster ME, et al. Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 

Pandemic [published online ahead of print, 2021 Apr 6]. JAMA Pediatr. 2021;e210630. doi:10.1001/jamapediatrics.2021.0630 

3. Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States. https://www.cdc.gov/mis-c/cases/index.html 

4. Payne et al, JAMA Netw Open. 2021;4(6):e2116420. doi:10.1001/jamanetworkopen.2021.16420 16 
Daily MIS-C cases and COVID-19 cases reported to CDC 

(7-day moving average) 

https://www.cdc.gov/mis-c/cases/index.html; accessed 06/08/2021 17 
 

 

Characteristics associated with Multisystem Inflammatory 

Syndrome in Adults (MIS-A) 

▪ Single-center, retrospective cohort study identified 15 adults with MIS-A from those hospitalized with 

a positive SARS-CoV-2 test result1 

– 15 (1.7%) of 839 hospitalized patients 

– Patients with MIS-A were younger and more likely to have positive serologic test (SARS-CoV-2 

antibodies) compared to acute COVID-19 patients. 

• Other demographic characteristics and comorbidities did not differ between MIS-A patients and 

patients with acute COVID-19 

– 8 of 15 MIS-A patients had cardiovascular involvement 

▪ Case series of 27 MIS-A patients2 

– Antibody testing required to identify SARS-CoV-2 infection in approximately one third of cases 

– Age range: 21 – 50 years 

– 26 (96%) patients belonged to racial or ethnic minority groups 

– Three patients died 

1. Davogustto et al, JAMA Netw Open. 2021;4(5):e2110323. doi:10.1001/jamanetworkopen.2021.10323 

2. Morris SB et al, MMWR Morb Mortal Wkly Rep 2020;69:1450–1456. DOI: http://dx.doi.org/10.15585/mmwr.mm6940e 18 
Epidemiology of myocarditis and pericarditis 

▪ Myocarditis is inflammation of the heart muscle, and pericarditis is inflammation of the 

outer lining of the heart 

▪ Myocarditis and pericarditis generally occur more frequently in: 

– Young adults 

– Men 

– Persons with certain medical conditions or recent medical procedure 

▪ Can occur after SARS-CoV-2 infection 

– Data to estimate frequency after COVID-19 is limited 

▪ There is a spectrum of disease but for the purpose of the benefit-risk discussion we will 

refer to both myocarditis and pericarditis as myocarditis 

Gubernot D, Vaccine. https://doi.org/10.1016/j.vaccine.2021.05.016 

https://www.nhlbi.nih.gov/health-topics/heart-inflammation 19 
 

 

 

Myocarditis and COVID-19 

▪ 1597 young athletes with recent SARS-CoV-2 infection had cardiac MRI1 

– 37 (2.3%) with abnormal MRI findings 

– However, 24 (65%) of 37 had normal lab findings and no symptoms 

– Another study suggested some MRI findings may be related to remodeling from athletic training2 

▪ Retrospective study — children with acute myocarditis treated at a single center from 2018–20203 

– 27 children <18 years of age identified 

– 7/27 (26%) had evidence of prior SAR-CoV-2 infection or exposure 

• 6 ultimately diagnosed with MIS-C 

– Individuals with myocarditis/MIS-C related to SARS-CoV-2 had better clinical course 

• None diagnosed with acute fulminant myocarditis 

• Shorter duration of inotropic drug support and ICU stay 

• Did not require mechanical respiratory support 

1Daniels CJ, et al. JAMA Cardiol. Pub online May 27, 2021. doi:10.1001/jamacardio.2021.2065; 2Clark DE, et al. Circulation; 2021:143(6): 3Vukomanovic et al. PIDJ;2021:40(5):e173-e17820 
 

 

 

 

Myocarditis after mRNA vaccines: 

Summary of clinical features 

▪ Most commonly in males <30 years of age 

▪ Symptom onset clusters in the week following vaccination 

▪ Early data of acute outcomes have been good 

–Many cases hospitalized, usually for short duration 

▪ No long-term data available yet 

–Continued monitoring ongoing 

Marshall et al. Symptomatic acute myocarditis in seven adolescents following Pfizer-BioNTech COVID- 19 vaccination. Pediatrics. 2021 

Larson et al. Myocarditis after BNT162b2 and mRNA-1273 Vaccination. 

Mouch et al. Myocarditis following COVID-19 mRNA vaccination. Vaccine. 2021 May 28;S0264-410X(21)00682-4. 21 
Summary 

▪ COVID-19 incidence, hospitalization, and mortality rates are decreasing overall 

– Variants continue to spread and scenarios exist in which cases increase in fall 

– Adolescents are growing proportion of cases given vaccine coverage among adults 

▪ Post COVID-19 conditions also impact adolescents and young adults 

– 4,018 MIS-C cases have been reported to national surveillance 

▪ Myocarditis is a disease marked by inflammation of the heart muscle 

– Risk factors include younger age and male sex 

– Can occur with SARS-CoV-2 infection 

▪ Myocarditis after mRNA vaccines noted with highest frequency in males aged 12–29 

years following 2nd dose 

– Early outcomes have been encouraging, but no long-term data available yet 

22 
Benefits and Harms 
COVID-19 mRNA vaccines in adolescents and young adults 

Benefits Potential harms 

Estimated COVID-19 cases and Estimated cases of 

hospitalizations prevented by myocarditis after mRNA 

mRNA COVID-19 vaccines, COVID-19 vaccines, 

by age and gender by age and gender 

24 
 

 

Benefits of the Pfizer-BioNTech COVID-19 vaccine 

▪ Clinical trial data demonstrated efficacy against symptomatic, laboratoryconfirmed COVID-19 among individuals ≥16 years of age

– Overall efficacy was 95% (95% CI: 90.3%, 97.6%) 

▪ Vaccine efficacy against COVID-19 associated hospitalization was 100% 

(95% CI: -9.9%, 100%) 

▪ Also demonstrated high efficacy against symptomatic, laboratory-confirmed 

COVID-19 in adolescents aged 12–15 years 

– Overall efficacy was 100%, immunogenicity non-inferior to 16–25 year old population 

Polack FP et al. N Engl J Med 2020; DOI: 10.1056/NEJMoa2034577 

Frenck RW et al. N Engl J Med 2021; DOI: 10.1056/NEJMoa2107456 25 
 

 

Benefits of the Moderna COVID-19 vaccine 

▪ Clinical trial data demonstrated efficacy against symptomatic, laboratory-confirmed 

COVID-19 among individuals ≥18 years of age 

– Overall efficacy was 94.1% (95% CI: 89.3%, 96.8%) 

▪ Vaccine efficacy against COVID-19 associated hospitalization was 89% 

(95% CI: 13%, 99%) 

Baden LR et al. N Engl J Med 2021; DOI: 10.1056/NEJMoa2035389 26 
Real-world effectiveness of mRNA COVID-19 vaccines 

▪ Multiple real-world effectiveness studies from the United States and other 

countries demonstrate that a two-dose mRNA COVID-19 vaccination series in 

age groups for which the vaccine is recommended is effective 

– Against SARS-CoV-2 infection: 64–99% estimate range 

– Against COVID-19-associated hospitalization: 87–97% estimate range 

https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html 27 
 

 

Potential harms of the mRNA COVID-19 vaccines: 

After dose 2 

▪ 133 million vaccine 2nd doses administered*and 636 reported myocarditis cases as of 

June 11, 2021 

– Additional potential myocarditis cases under review 

Females Males 

Age group Cases§ Doses admin Reporting rate† Cases§ Doses admin Reporting rate†

12-17 years old 19 2,189,726 8.68 128 2,039,871 62.75 

18-24 years old 23 5,237,262 4.39 219 4,337,287 50.49 

25-29 years old 7 4,151,975 1.69 59 3,625,574 16.27 

30-39 years old 11 9,356,296 1.18 61 8,311,301 7.34 

40-49 years old 18 9,927,773 1.81 34 8,577,766 3.96 

50-64 years old 18 18,696,450 0.96 18 16,255,927 1.11 

65+ years old 10 21,708,975 0.46 11 18,041,547 0.61 

§ Cases reported through VAERS using a 7-day risk window 

* Source of doses administered: https://covid.cdc.gov/covid-data-tracker/#vaccinations; Some age- and sex-specific doses administered data were imputed 

†Reporting rate = myocarditis cases per 1 million mRNA COVID-19 vaccine doses administered 28 
 

 

Summary of benefit-risk analyses 

Individual Level Benefit-Risk Analysis 

• Evaluate direct benefits and risk, per million mRNA COVID-19 vaccine doses 

• Examine sex and age differences in risk and benefits 

• Calculations based on: 

• Recent COVID-19 case and hospitalization incidence 

• mRNA vaccine efficacy 

• mRNA vaccinations to date 

• Number of persons already vaccinated 

• Myocarditis risk within 7 days after dose 2 

• 120-day risk period 

Population Level Considerations 

• Describe benefits of vaccination at population level 

29 
657 Hospitalizations* Prevented

Benefits and risks after dose 2, by age group 

For every million doses of mRNA vaccine given with current US exposure risk1 

COVID-19-Associated 

Hospitalizations Prevented 

Cases of Myocarditis 

12 – 17 

18 – 24 

25 – 29 

30 – 39 

40 – 49 

50 – 64 

65+ 

3145 

9027 

2000 1500 1000 500 0 0 500 1000 1500 2000 

1 Based on hospitalization rates from COVID-NET as of May 22nd. Benefit/Risk calculated over 120 days. 30 
657 Hospitalizations* Prevented

Benefits and risks after dose 2, by age group 

For every million doses of mRNA vaccine given with current US exposure risk1 

COVID-19-Associated Cases of Myocarditis 

Hospitalizations Prevented 

12 – 17 

18 – 24 

25 – 29 

30 – 39 

40 – 49 

50 – 64 

65+ 

3145 

9027 

2000 1500 1000 500 0 0 500 1000 1500 2000 

1 Based on hospitalization rates from COVID-NET as of May 22nd. Benefit/Risk calculated over 120 days. 31 
Predicted cases prevented vs. myocarditis cases for every 

million second dose vaccinations over 120 days 

Females 12–17 Years 

8,500 COVID-19 cases prevented 

183 hospitalizations prevented 

38 ICU admissions prevented 

1 death prevented 

8–10 myocarditis cases 

Males 12–17 Years 

5,700 COVID-19 cases prevented 

215 hospitalizations prevented 

71 ICU admissions prevented 

2 deaths prevented 

56–69 myocarditis cases 

Hospitalizations, ICU admissions and deaths based on data for week of May 22, 2021. 32 
Predicted cases prevented vs. myocarditis cases for every 

million second dose vaccinations over 120 days 

Females 18–24 Years Males 18–24 Years 

14,000 COVID-19 cases prevented 

1,127 hospitalizations prevented 

93 ICU admissions prevented 

13 deaths prevented 

4–5 myocarditis cases 

12,000 COVID-19 cases prevented 

530 hospitalizations prevented 

127 ICU admissions prevented 

3 deaths prevented 

45–56 myocarditis cases 

Hospitalizations, ICU admissions and deaths based on data for week of May 22, 2021. 33 
Predicted cases prevented vs. myocarditis cases for every 

million second dose vaccinations over 120 days 

Females 24–29 Years Males 24–29 Years 

15,000 COVID-19 cases prevented 

1,459 hospitalizations prevented 

87 ICU admissions prevented 

4 deaths prevented 

2 myocarditis cases 

15,000 COVID-19 cases prevented 

936 hospitalizations prevented 

215 ICU admissions prevented 

13 deaths prevented 

15–18 myocarditis cases 

Hospitalizations, ICU admissions and deaths based on data for week of May 22, 2021. 34 
Additional considerations for direct benefit and risk 

Males 12–17 Years Additional benefits to prevent 

post-COVID conditions 

Prevention of MIS-C 

Prevention of prolonged symptoms 

Protection against variants 

35 
Benefit-risk analyses 

Population Level Considerations 

▪ No alternatives to mRNA vaccines for the foreseeable future in adolescents 

▪ Vaccination of students offers an added layer of protection against COVID-19 and 

can be an important tool to return to ‘normal’

▪ Higher levels of vaccination coverage can lead to less community transmission, 

which can protect against development and circulation of emerging variants 

▪ Racial and ethnic minority groups have higher rates of COVID-19 and severe disease1 

– Potential changes in vaccine policy, or anything that would impact vaccination coverage for 

adolescents/young adults may disproportionately impact those groups with highest rates of 

poor COVID-19 outcomes 

1. https://covid.cdc.gov/covid-data-tracker/#demographics 36 
Benefit-risk interpretations and limitations 

▪ Direct benefit-risk assessment shows positive balance for all age and sex groups 

– Considers individual benefits of vaccination vs. individual risks 

– Benefits are likely an underestimate 

• Analysis was performed using reported rates of cases and hospitalizations 

• Likely represent only a fraction of the true cases that have occurred in the population 

– Still uncertainty in rates of myocarditis after mRNA vaccines 

• Not all cases are verified and crude rates were used 

▪ Balance of risks and benefits varies by age and sex 

– Balance could change with increasing or decreasing incidence 

▪ Limited data currently on risk of myocarditis in 12–15 year old population 

– Due to timing of recommendations, limited number of 2nd doses given 

37 
Clinical Considerations
Vaccine considerations in people with a history of 

myocarditis or pericarditis 

Scenario Recommendation 

Pericarditis prior to COVID-19 vaccination Receive any FDA-authorized COVID-19 vaccine 

Pericarditis after 1st dose of an mRNA 

COVID-19 vaccine but prior to 2nd dose 

Myocarditis prior to COVID-19 vaccination 

Myocarditis after 1st dose of an mRNA 

COVID-19 vaccine but prior to 2nd dose 

Proceed with a 2nd dose of mRNA COVID-19 

vaccine after resolution of symptoms. 

Discuss with patient, guardian, and clinical team 

Receive any FDA-authorized COVID-19 vaccine if 

heart has recovered 

Defer 2nd dose of mRNA COVID-19 vaccine until 

more information is known 

However, if heart has recovered, could consider 

proceeding with 2nd dose under certain 

circumstances. Discuss with patient, guardian, 

and clinical team 
WORK GROUP 

INTERPRETATION
COVID-19 mRNA vaccines in adolescents and young adults: 

Benefit-risk discussion 

Work Group Interpretation 

• Initial presentations are reassuring; however, continued monitoring of 

cases, clinical course, and long-term outcomes of myocarditis after mRNA 

vaccines will be important 

• Need to follow the benefit-risk balance as we learn more around 

myocarditis, as well as updates to epidemiology (cases, variants, etc) 

• Currently, the benefits still clearly outweigh the risks for COVID-19 

vaccination in adolescents and young adults 

41 
COVID-19 mRNA vaccines in adolescents and young adults 

Current COVID-19 vaccine policy 

▪ COVID-19 vaccines are recommended for persons 12 years of 

age and older in the United States under FDA’s Emergency Use 

Authorization 

42 
Questions for ACIP 

1. What does ACIP think about the benefit-risk balance of COVID-19 

vaccines in adolescents and young adults, in the setting of reports of 

myocarditis? 

2. What additional information or analyses could inform these discussions 

as we continue to closely monitor this situation? 

43 
Acknowledgements 

▪ Stephen Hadler 

▪ Gayle Langley ▪ COVID-19 Vaccine Task Force 

▪ Julia Gargano▪ Vaccine Safety Team 

▪ Jessica MacNeil▪ Immunization team 

▪ Heather Scobie▪ Epi Task Force 

▪ Danielle Moulia

– MIS-C unit 

– COVID-NET 

▪ Mary Chamberland

▪ Nicole Reisman

▪ Data, Analytics and Visualization Task 

Force 

▪ Jack Gersten

▪ Division of Healthcare Quality Promotion 

▪ Eddie Shanley ▪ Respiratory Viruses Branch 

▪ Hannah Rosenblum