06 COVID Panagiotakopoulos 508

National Center  for Immunization and Respiratory Diseases
Evidence to Recommendations Framework:
2024 -2025 COVID -19 Vaccines in Persons ≥6 Months of Age
Lakshmi Panagiotakopoulos, MD, MPH
ACIP Meeting
June 27, 2024

 Evidence to Recommendations (EtR) Framework
Policy Question
• Should 2024 – 2025 COVID -19 vaccines be recommended for use in persons
≥6 months of age?
• Products and ages under review for authorization or approval by FDA
include:
-Moderna COVID -19 vaccine for ages 6 months and older
-Novavax COVID -19 vaccine for ages 12 years and older
-Pfizer -BioNTech COVID -19 vaccine for ages 6 months and older
FDA: Food and Drug Administration 2
EtR Domain:
Public Health Problem

 Weekly population -based rates of COVID -19-associated hospitalizations,
by age group — COVID -NET, May 6, 2023 – May 11, 2024 Rate per 100,000 population 70
60
50
40
30
20
10
0
Week Ending Date
<6 months 6 months –4 years 5–11 years 12–17 years
18–49 years 50–64 years 65–74 years ≥75 years
CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed June 17, 2024 4

    Monthly rates of COVID -19-associated deaths by age group,
United States, May 1, 2023 – April 30, 2024
Age Group
Provisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID -19, co ded as ICD –10 code U07.1, on the death certificate. Death data are displayed by date
of death (event).
Source: Provisional data from the CDC’s National Center for Health Statistics (NCHS) National Vital Statistic System (NVSS); CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -
tracker/#demographicsovertime . Accessed June 16, 2024 5

     Weekly number of COVID -19-associated deaths reported to
CDC, United States, June 3, 2023 – June 8, 2024
The most recent 3 weeks of mortality counts are shaded grey because NVSS reporting is <95% during this period.
Provisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID -19, co ded as ICD –10 code U07.1, on the death certificate. Death data are displayed by date of
death (event). Data include underlying and contributing causes of death.
CDC COVID Data Tracker. National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS ). https://covid.cdc.gov/covid -data -tracker/#trends_weeklydeaths_select_00 . Accessed June 17, 2024 6
Total number of COVID -19-associated deaths1,2 in 2023, by age group,
United States
50000
44,05945000
58 44 81 819 4815
0 5000 10000 15000 20000 25000 30000 35000 40000 Number of Deaths
1

< 1 year 1-4 years 5-19 years 20-44 years 45-64 years ≥65 years
1

       Provisional data
2 Underlying cause of death
Source: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. Data are from the final Multiple Cause of
Death Files, 2018 -2022, and from provisional data for years 2023 -2024, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes COVID -
19 code (U07.1) as the underlying cause of death. Accessed at http://wonder.cdc.gov/mcd -icd10 -provisional.html on June 5, 2024 7

                Total number of COVID -19 and Influenza -associated deaths1,2 in 2023,
by age group, United States
90 81
58
44
17 39 71
0 10 20 30 40 50 60 70 80 Number of Deaths
1
< 1 year 1-4 years 5-19 years
COVID-19 Influenza
1 Provisional data
2 Underlying cause of death
Source: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. Data are from the final Multiple Cause of
Death Files, 2018 -2022, and from provisional data for years 2023 -2024, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes
influenza codes (J09 -J11) or COVID -19 code (U07.1) as the underlying cause of death. Accessed at http://wonder.cdc.gov/mcd -icd10 -provisional.html on June 5, 2024
Note: Estimates of pediatric influenza deaths reported to CDC can be found here: https://www.cdc.gov/flu/weekly/index.htm . Estimates will vary due to differences in reporting methods and timeframes used. 8

    Variant Predominant Period Dates Number of MIS-C Incidence per 1,000,000 Median
Cases person -months (95% CI) Age (IQR),
years
Pre-Delta Oct 15, 2020 –Apr 5, 2021 3,284 6.79 (6.56 –7.03) 9.2 (5.4 –13.1 )
Delta Jul 10 –Dec 24, 2021 2,300 4.90 (4.70 –5.10) 9.1 (5.5 –12.3)
Omicron BA.1/BA 1.1 Jan 1 –Ap 8, 2022 1,149 4.21 (3.98 –4.46) 7.5 (4.1 –11.5)
Omicron BA.2/BA.4/BA.5 April 9 –Dec 31, 2022 422 0.56 (0.51 –0.62) 5.4 (2.8 –9.8)
2023 Omicron subvariants Jan 1 –Dec 31, 2023 117 0.11 (0.10 –0.14) 6.9 (3.4 –11.5)
Cases from 2023 were clinically similar to those with MIS -C illness onset in 2021 -2022
58% were previously healthy with no underlying medical conditions
50% required ICU -level care, 34% had shock, and 27% had cardiac dysfunction
3 deaths
MISC: Multisystem Inflammatory Syndrome in Children 9
▪ Incidence by SARS- CoV-2 variant-predominant periods, defined using surveillance data and allowing
for 2 weeks to MIS-C onset from when a variant exceeded 50%  circulating lineages

 Underlying Medical Conditions among Patients
Admitted to ICU among Children and Adolescents Ages
≤17 Years with COVID -19-associated Hospitalization,
July 2023 –March 2024
Age category Among all
hospitalized
children, % with
no underlying
conditions Among those
admitted to ICU, %
with no underlying
conditions
(n=363)
Overall ≤17 Years 50% 40% Among those with no
underlying conditions,
what % were admitted
to ICU?
(n=791)
18%
Hospitalizations are limited to those with COVID -19 as the presenting complaint upon admission. 10

          Other pediatric vaccine preventable diseases: Annual hospitalizations
per 100,000 population prior to vaccine recommendation compared
to COVID -19
Hepatitis A1 Varicella2
(Chickenpox) Vaccine -type
Invasive
Pneumococcal
Disease3 COVID -194
Age 5–14 years 0–4 years 0–4 years 6 months –<18 years
Time period 2005 1993 –1995 1998 –1999 2022 –2023 2023 –2024
Hospitalization
Burden
(Annual rate per
100,000 population) <1 29-42 405 6 months –
4 years: 74
5–11 years : 17
12–17 years: 24 6 months –
4 years: 50
5–11 years : 10
12–17 years: 13
1 https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5603a1.htm
2Davis MM, Patel MS, Gebremariam A. Decline in varicella -related hospitalizations and expenditures for children and adults after introduction of varicella vacci ne in the United States. Pediatrics. 2004;114(3):786 -792.
doi:10.1542/peds.2004 -0012
3 Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7 -valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease --United
States, 1998 -2003. MMWR Morb Mortal Wkly Rep. 2005 Sep 16;54(36):893 -7. PMID: 16163262.
4 COVID -NET data October 2022 – September 2023 and October 2023 – May 2024. COVID -19 rates have not been adjusted for reason for admission. COVID vaccine first introduced in 12 -17 years in May 2021; in 5 -11
years in November 2021 and in 6 months – 4 years in June 2022
5 Vaccine -type invasive pneumococcal disease annual rate for children <5 years in 1998 -1999 was 80 per 100,000, of which about 50% were hospitalized. 11

                Pediatric vaccine preventable diseases: Deaths per year in the United
States prior to vaccine recommendation compared to COVID -19
Hepatitis A1 Meningococcal
(ACWY)2 Varicella3 Rubella4 Rotavirus5 COVID -196
Age <20 years 11–18 years 5–9 years All ages <5 years 6 months –19 years
Time
period 1990 –1995 2000 –2004 1990 –1994 1966 –1968 1985 –1991 2023
Average
deaths
per year 3 8 16 17 20 1–4 years : 44
5–19 years: 81
1Vogt TM , Wise ME, Bell BP, Finelli L. Declining hepatitis A mortality in the United States during the era of hepatitis A vac cination. J Infect Dis2008; 197:1282 –8.
2National Notifiable Diseases Surveillance System with additional serogroup and outcome data from Enhanced Meningococcal Disea se Surveillance for 2015 -2019.
3Meyer PA, Seward JF, Jumaan AO, Wharton M. Varicella mortality: trends before vaccine licensure in the United States, 1970 -1994. J Infect Dis. 2000;182(2): 383-390. doi:10.1086/315714
4Roush SW , Murphy TV; Historical comparisons of morbidity and mortality for vaccine -preventable diseases in the United States. J AMA 2007; 298:2155 –63.
5 Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimat es of disease burden. J Infect Dis. 1996 Sep;174 Suppl 1:S5 -11
6 http://wonder.cdc.gov/mcd -icd10 -provisional.html on May 14 2024 . COVID vaccine first introduced in 12 -17 years in May 2021; in 5 -11 years in November 2021 and in 6 months – 4 years in June 2022 12
Domain Equity Question:
Does the problem impact all populations equally?
      Age-adjusted cumulative COVID -19 hospitalizations per 100,000 population
by race and ethnicity — COVID -NET, October 2023 – May 2024
CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed June 20, 2024 14

  Summary
Public Health Problem
• COVID -19-associated hospitalizations and deaths occur all year around, but peak in
December – February
• COVID -19-associated hospitalizations and deaths are highest in adults aged 75 and older
• More pediatric hospitalizations and deaths occur each year associated with COVID -19 than
other select vaccine preventable diseases as the time those recommendations were made
for children in the United States
-Among children hospitalized for COVID -19, 50% had no underlying medical conditions
-Of those, 18% were admitted to the ICU
• Racial and ethnic differences in COVID -19 hospitalization rates persist
ICU: Intensive Care Unit 15
o o o o o o
    Public Health Problem
Work Group Interpretation
Is COVID -19 disease among persons ≥6 months of age of public health
importance?
 No Probably no Probably yes  Yes Varies  Don’t know
EtR Domain:
Benefits and Harms

 Summary of available data
• Benefits and harms of COVID -19 vaccines are based on multiple years of data from
original, bivalent, and 2023 -2024 formula COVID -19 vaccines
-GRADE
• Benefits and harms of updated (bivalent or 2023 -2024) COVID -19 vaccines
-Available data on GRADE outcomes with no studies captured in systematic review
-Real -world safety and effectiveness monitoring of the 2023 -2024 vaccines
-Modeling data on potential impact of 2024 -2025 COVID -19 vaccine
recommendations
18

 GRADE of benefits and harms for 2024 -2025 COVID -19
vaccine: PICO questions
Adults and Adolescents Infants and Children (Pediatric)
Population Persons ages 12 years and older Persons ages 6 months -11 years
Intervention Updated COVID -19
vaccine (bivalent or 2023 -2024) Updated COVID -19
vaccine (bivalent or 2023 -2024)
Comparison No updated vaccine* No updated vaccine*
Outcomes 1. Medically -attended COVID -19 (ED/UC
visits)
2. Hospitalization due to COVID -19
3. Death due to COVID -19
4. Post -COVID Conditions
5. Specified serious adverse events 1. Medically -attended COVID -19 (ED/UC
visits)
2. Hospitalization due to COVID -19
3. Death due to COVID -19
4. MIS-C
5. Post -COVID conditions
6. Specified serious adverse events
PICO: Population, intervention, comparison, outcomes;  ED/UC: emergency department/urgent care; MIS -C: multisystem inflammatory syndrome in children
*May include people who received any number of doses of prior formulations and unvaccinated
Bolded outcomes are critical; unbolded outcomes are important 19
GRADE benefits among adolescents and adults: Forest plot and pooled
VE estimate against medically -attended COVID -19 (ED/UC visits) (n=5)

a
Notes:
ED/UC: emergency department/urgent care; VE or vaccine eff.= vaccine effectiveness; CI= confidence intervals ; IV= inverse variance; nr= not reported
Studies are listed on the y -axis by median days since receipt of an updated dose. Pooled vaccine effectiveness based on a random effects meta -analysis, using adjusted VE estimates on a log
scale.
Vaccine effectiveness comparisons included an updated dose (either bivalent or 2023 -2024 formulation) compared to no updated dos e (may include people who received any number of doses of
prior formulations and unvaccinated, definitions varies by included study).
a Author, vaccine formulation, and time since vaccination (median or median range)
*VE estimate among immunocompetent persons only
All studies are case control studies, 1 study is a pre -print, and 3 studies are manufacturer -funded.
In sensitivity analyses of pre-prints, manufacturer -funded studies, bivalent vaccine studies, and 2023 -2024 dose studies, the pooled VE point estimates remained stable, and 95% CIs overlapped. 20
GRADE benefits among adolescents and adults: Forest plot and
pooled estimate for VE against hospitalization due to COVID -19
(n=8)
Notes:
VE or vaccine eff.= vaccine effectiveness; CI= confidence intervals ; IV= inverse variance; nr= not reported
Studies are listed on the y -axis by median days since receipt of an updated dose. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. a

                 Vaccine effectiveness comparisons included an updated dose (either bivalent or 2023 -2024 formulation) compared to no updated dos e (may include people who received any number of doses of prior formulations and unvaccinated,
definitions varies by included study).
a Author, vaccine formulation, and time since vaccination (median or median range)
* Estimate among immunocompetent persons only
**Maximum follow -up time was 105 days
*** Maximum follow -up time was 112 days
6 studies are case control studies, 3 studies are cohort studies, 3 studies are pre -prints, and 3 studies are manufacturer -funde d.
In sensitivity analyses that excluded cohort studies, case control studies, pre -prints, manufacturer funded studies, bivalent va ccines, and 2023 -2024 doses, the pooled VE point estimates remained stable, and 95% CIs overlapped. 21
GRADE benefits among adolescents and adults: Forest plot and
pooled VE estimate against death due to COVID -19 (n=3)
a
Notes:
VE or vaccine eff.= vaccine effectiveness; CI= confidence intervals ; IV= inverse variance; nr= not reported

             Studies are listed on the y -axis by median days since receipt of an updated dose. Pooled VE based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale
Vaccine effectiveness comparisons included an updated dose (either bivalent or 2023 -2024 formulation) compared to no updated dos e (may include people who received any number of doses of prior formulations and unvaccinated,
definitions varies by included study).
a. Author, vaccine formulation, and time since vaccination (median or median range)
*Maximum follow -up time was 105 days
** Maximum follow -up time was 112 days
1 study is a case control study, 2 studies are cohort studies , 1 study is a pre -print , and 1 study is funded by a manufacturer
In sensitivity analyses of pre-prints and manufacturer -funded studies, the pooled VE point estimates remained stable, and 95% CIs overlapped
22

 Interpreting a GRADE certainty assessment
• A certainty assessment reflects our confidence that the true effect lies close to the estimated
effect
• There are 4 certainty levels:
• High: We are very confident that the true effect lies close to that of the estimated effect. Randomized controlled trial
certainty starts here and can be downgraded or upgraded1 .
• Moderate: We are moderately confident that the true effect lies close to the estimated effect, but there is a possibility
that it is substantially different.
• Low: We have limited confidence that the true effect lies close to the estimated effect; the true effect may be
substantially different from the estimated effect. Observational certainty starts here and can be downgraded or
upgraded1 .
• Very low: We have very limited confidence that the true effect lies close to the estimated effect; the true effect is likely
to be substantially different from the estimated of effect.
• A certainty assessment does not reflect our confidence in the quality of the individual studies or the
overall confidence in benefits and harms of the vaccine, which may be informed by additional data
on benefits and harms.
1. Evidence type may be downgraded due to risk of bias, inconsistency, indirectness, imprecision or other considerations such as publication bias and upgraded for indications of a dose -response
gradient, large or very large magnitude of effect, and opposing residual confounding. 23
Summary of GRADE
Outcome Population  Importance Design Effect Findings Final
(# of studies)  estimate certainty
(95% CI) assessment
Benefit
Adolescent/adult    Updated COVID -19 vaccine prevents hospitalization due t Low
Hospitalization due
to COVID -19Pediatric Critical OBS (8)   VE: 44 (34 -
53)    COVID -19, although the body of evidence in the pediatric
   population is limited to indirect data from adolescents
 and adults. Very low
 Death due to
COVID -19 Adolescent/adult
Pediatric Important OBS (3)   VE: 23 (8 -36)     Updated COVID -19 vaccine prevents death due to COVID -
  19, although the body of evidence in the pediatric
 population is limited to indirect data from adolescents
 and adults. Low
Very low
Post -COVID
conditions Adolescent/adult
Pediatric Important OBS (0) -- -
MIS-C Pediatric Important OBS (0) - - -
Harms
Critical -Low
Very low s

o

ED/UC: emergency department/urgent care; OBS: observational; VE: vaccine effectiveness; CI: confidence interval; MIS -C: multisys tem inflammatory syndrome in children
Note:  Vast majority of data captured in systematic review are for mRNA vaccines. 24 Medically -attended
  COVID -19 (ED/UC
visit) Adolescent/adult
Pediatric Critical OBS (5)
OBS (1)   VE: 43 (30 -
54)
  VE: 80 (42 -
96)      Updated COVID -19 vaccine is effective in preventing
   medically attended COVID -19 ED/UC visits. Low
Low
Specified serious
adverse eventsAdolescent/adult
Pediatric OBS (2)  In post -authorization safety monitoring, two rare adverse
   events have been associated with vaccination

    2023 -2024 Formula COVID -19 vaccine effectiveness
• 2023 -2024 COVID -19 vaccination provided increased protection against symptomatic SARS -CoV-2 infection and COVID -19-associated ED/UC visits and hospitalizations compared to no 2023 -2024 vaccine dose
• Waning patterns appeared similar to previous COVID -19 vaccine formulations; most durable protection appeared to be for critical illness, though statistical power was lacking in the longest time period since vaccination
• As with previous COVID -19 vaccine formulations, effectiveness was similar across age groups
• Receipt of 2023 -2024 COVID -19 vaccine provided protection against JN.1 and other circulating variants, though may be lower than protection provided against XBB sublineage variants
ED: Emergency department | UC: Urgent care
25

  COVID -19 mRNA vaccination associated with reduced occurrence
of Post -COVID Conditions (PCC) following SARS -CoV-2 infection
Among children 5 – 17 years:
Completion of the original formula
COVID -19 vaccine series prior to
infection associated with reduced
likelihood of symptoms:
34% for 1 or more PCC symptoms
47% for respiratory PCC symptoms
48% for 2 or more PCC symptoms Among adults:
3 doses of original formula COVID -19
vaccine prior to infection associated with
reduced likelihood of symptoms:
24% for 2 or more PCC symptoms
27% for cardiovascular/respiratory
symptoms
42% for gastrointestinal symptoms
26% for neurological symptoms
33% for other non -specific symptoms
Unpublished data from the HEROES/RECOVER, PROTECT cohorts.
HEROES Protocol ; RECOVER Protocol ; PROTECT Protocol 26

      COVID -19 vaccine effectiveness against Multisystem
Inflammatory Syndrome in Children (MIS -C) in US
children ages 5 -18 years old
• Multicenter case -control public health investigation from July 1, 2021 –April 7, 2022
• Compared odds of receiving 2 doses of BNT162b2 vaccine ≥28 days before admission between MIS -C
case -patients and hospital -based controls who tested negative for SARS -CoV-2
-304 MIS-C case patients ( 92% unvaccinated)
-502 controls (69% unvaccinated)
• A lower proportion of vaccinated patents required life
support or died during period of Delta
variant predominance
• One unvaccinated MIS -C case -patient (12 –18 years)
required ECMO, and 1 unvaccinated patient (5 –11
years) died
Zambrano LD, et al. Clin Infect Dis. 2022 Aug 4:ciac637 ECMO = extracorporeal membrane oxygenation
 27

 COVID -19 vaccine safety
• COVID -19 vaccines have a favorable safety profile as demonstrated by
robust safety surveillance over 3 years of COVID -19 vaccine use
-Anaphylactic reactions have been rarely reported following receipt of COVID -19
vaccines
-Rare risk of myocarditis and pericarditis predominately in males ages 12 -39 years
• No myocarditis or pericarditis signal in the Vaccine Safety Datalink for the
2023 -2024 Formula COVID -19 vaccine, however, this may be limited by low
uptake
-Reactogenicity symptoms are overall less frequent and severe among older adults
compared with adolescents and younger adults
28

 Longer term impact of vaccine associated myocarditis
•Vaccine -associated myocarditis is a rare risk of COVID -19 vaccination.
•Acute clinical picture tends to resolve quickly1
-Majority of patients had recovered at 90 days with symptoms improving over time
•Small subset with persistent MRI findings (e.g., late gadolinium
enhancement), with unclear correlation to symptoms2
-Additional follow up is needed to determine the long -term impact of these MRI
findings
1.https://www.sciencedirect.com/science/article/pii/S2352464222002449?via%3Dihub
2.https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4681858#:~:text=Interpretation%3A%20COVID%2D19%20vaccine%2D,continued%20s urveillance%20in%20C%2DVAM
MRI: magnetic resonance imaging 29

  Summary of the Vaccine Safety Datalink (VSD) Rapid
Cycle Analysis for the 2023 -2024 COVID -19 vaccine
• The VSD identified two statistical signals for mRNA COVID -19 vaccines during the 2023 -2024 season
-Guillain -Barré syndrome (GBS) following Pfizer COVID -19 vaccine among people aged ≥65 years
• An association between mRNA COVID -19 vaccines and GBS had not been observed prior to this season in
VSD or other systems
• The increased rate ratio observed during the 2023 -2024 season may or may not represent a true risk
• If there is a true risk, it is estimated to be similar to what is considered acceptable for other adult vaccines
-Ischemic stroke following Moderna (aged ≥65 years) and Pfizer (aged 50 -64 years) COVID -19 vaccines
• The VSD previously observed a statistical signal for ischemic stroke during 2022 -2023 for bivalent Pfizer
COVID -19 vaccine (aged ≥65 years)
• Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke with
mRNA COVID 19 vaccines
• No other new or unexpected safety concerns were identified for the 2023 -2024 COVID -19 vaccines
• Any real or theoretical risks of vaccine adverse events need to be placed in the context of the benefits
of COVID -19 vaccines in preventing COVID -19 and its potentially serious complications 30

 Models of potential impact of different 2024 -2025
COVID -19 vaccine recommendations
• Assumptions of COVID -19 Scenario Modeling Hub Round 18
• Six scenarios focusing on three vaccine recommendation scenarios under high and
low rates1 of immune escape
-No vaccine recommendation2 vs recommendation only for persons at high -risk vs
universal recommendation
-High -risk defined as those ages ≥ 65 years and those with underlying conditions3
• Vaccine uptake assumptions based on 2023 -2024 COVID -19 vaccine coverage4
• Assumes vaccine available on September 1st with 75% VE against hospitalization
-Constant rate of immune escape and waning applied starting September 1st
• Models projected 1 year into the future
1. Low immune escape occurs at a constant rate of 20% per year and high immune escape occurs at a constant rate of 50% per year
2. The no vaccine recommendation scenario allowed for naïve children aging into eligibility to be vaccinated
3. Ko JY, Danielson ML, Town M, et al. Risk Factors for Coronavirus Disease 2019 (COVID -19)–Associated Hospitalization: COVID -19–Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance
System. Clinical Infectious Diseases. 2021;72(11):e695 -e703. doi:10.1093/ cid/ciaa1419
4. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/index.html . Assumption of approximately 21% of adults, 39% of those ≥65 years, 32% of those with underlying conditions
VE: vaccine effectiveness 31
Universal vaccine recommendations projected to prevent about
30,000 more hospitalizations over the next year compared with
a risk -based recommendation
Recommendation
Type1Percent prevented (95% CI) Total prevented (95% CI)
Universal v. None
High -Risk v. None
Universal v. High -Risk

1.None = no vaccine recommendation; High -risk = recommended for those ages ≥ 65 years and those with underlying conditions; Uni versal = universal vaccine recommendation 32
Domain Equity Question:
Are the desirable and undesirable anticipated effects demonstrated across
all populations equally?

 Are the desirable and undesirable anticipated effects
demonstrated across all populations equally?
• There is no evidence to suggest that COVID -19 vaccine effectiveness
varies substantially by race/ethnicity1,2
-Differences in vaccine hesitancy/uptake, crowding, access to care, and prior
infection could impact vaccine effectiveness and these factors may also differ by
race/ethnicity
• There is no evidence to suggest that COVID -19 vaccine safety profiles vary by
race/ethnicity, however risk has been shown to differ by age and sex
-Risk for myocarditis is highest in adolescent and young adult males
• Benefits and harms for the U.S. population are best assessed when clinical trial and
study populations are optimally representative of the U.S. population
1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619452/
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763212/ 34

 Summary
Benefits and Harms
• 2023 -2024 COVID -19 vaccine is effective in preventing ED/UC visits and preventing
severe outcomes related to COVID -19 (e.g., hospitalization, death); waning of
immunity is expected
• COVID -19 vaccines continue to have a favorable safety profile as
demonstrated by robust safety surveillance over 3 years of COVID -19 vaccine use
-Ischemic stroke and GBS signals in the VSD are not clear or consistent, and
are seen in the age groups (adults ≥ 50 years and adults ≥ 65 years,
respectively) with the highest burden of disease that would benefit the most from
updated COVID -19 vaccination
• Modeling projects more hospitalization averted when 2024 -2025 COVID -19 vaccines
are universally recommended compared to no recommendation or recommended
only for those at high risk
VSD: Vaccine Safety Datalink | GBS: Guillain -Barre Syndrome 35

 Benefits and Harms
How substantial are the desirable anticipated effects?
• How substantial are the anticipated effects for each main outcome for
which there is a desirable effect?
o o o o o o    Minimal  Small Moderate  Large Varies  Don’t know
o o o o o o

  Benefits and Harms
How substantial are the undesirable anticipated effects?
• How substantial are the anticipated effects for each main outcome for
which there is an undesirable effect?
 Minimal  Small  Moderate  Large Varies  Don’t know
 Benefits and Harms
Do the desirable effects outweigh the undesirable effects?
• What is the balance between the desirable effects relative to the
undesirable effects?
oFavors intervention (2024 – 2025 Formula COVID -19 vaccine)
oFavors comparison (no vaccine)
oFavors both
oFavors neither
oUnclear
 EtR Domain:
Values

   1 in 5 Americans now say COVID -19 is a major threat
to public health
% of U.S. adults who say COVID -19 is a major threat to the health
of the U.S. population
80
47 66 64 67 65 63 61
57
41
20
20 30 40 50 60 70
10
0
Mar '20 Mar '20 Apr '20 Jul '20 Nov '20 Feb '21 Aug '21 Jan '22 May '22 Feb '24
Pew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-
coronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 40

  Concern about risk of COVID -19 by age, February 2024
% of U.S. adults who say they are very/somewhat concerned that they…
Survey conducted among 10,133 U.S. adults from February 7 -11, 2024.
Pew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-
coronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 12 14 10 16
29 26 28 28
0 10 20 30 40 50 65+ 50-6430-2918-29Age, years Might unknowingly spread
COVID -19 to others
very concerned Somewhat concerned 11 11 8 10
21 18 14 16
0 5 10 15 20 25 30 35 65+ 50-6430-4918-29Age, years Will get COVID -19 and
require hospitalization
Very concerned Somewhat concerned
41

  Key attitudes and experiences among parents of children 6 months -17 years, December 2023
National Immunization Survey -Child COVID -19 Module (NIS -CCM)
COVID -19 Vaccination Key Attitudes and Experiences by Age Group Among Parents of Children Ages
6 Months -17 Years, NIS -CCM, December 2023
80
30 35 51
28 39 56
30 57 69
0 10 20 30 40 50 60 70 Percent
Moderately or very concerned about child getting COVID-19 Confidence that COVID-19 vaccine is very or completely safe for Confidence that COVID-19 vaccine is somewhat or very
disease child important to protect child
6 months - 4 years 5 - 11 years 12 - 17 years
The December estimates are based on data collected November 26 through December 30, 2023.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed April 30, 2024 42

  Key attitudes and experiences among adults 18 years and older, April 2024
National Immunization Survey -Adult COVID Module (NIS -ACM)
COVID -19 Vaccination Key Attitudes and Experiences by Age Group Among Adults Ages ≥18
Years, NIS -ACM, April 2024
80
21 51 64
30 55 65
35 63 74
0 10 20 30 40 50 60 70 Percent
Very or moderately concerned about COVID-19 disease Confidence COVID-19 vaccine is very or completely safe Confidence that COVID-19 vaccine is somewhat or very
important to protect me
18 - 49 years 50 - 64 years 65+ years
The April estimates are based on data collected April 1 through April 27, 2024.
CDC.COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 30, 2024 43

 EtR Domain:
Is there important variability in how patients or populations value the
outcome?

   Key attitudes and experiences among parents of children 6 months -17 years,
December 2023
National Immunization Survey -Child COVID -19 Module (NIS -CCM)
COVID -19 Vaccination Key Attitudes and Experiences by Race & Ethnicity Among Parents of
Children Ages 6 Months -17 Years, NIS -CCM, December 2023
80
33 47 68
23 45 51
43
40 70
30 44 67
0 10 20 30 40 50 60 70 Percent Hispanic
White, non-Hispanic
Black, non-Hispanic
Other or multiple races, non-Hispanic
Moderately or very concerned about child getting
COVID-19  disease Confidence COVID-19 vaccine is very or completely
safe for  child Confidence that COVID-19 vaccine is somewhat or
very important to protect child
The December estimates are based on data collected November 26 through December 30, 2023.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed April 30, 2024 45

  Key attitudes and experiences among adults 18 years and older, April 2024
National Immunization Survey -Adult COVID Module (NIS -ACM)
COVID -19 Vaccination Key Attitudes and Experiences by Race & Ethnicity Among Adults Age ≥18 Years, NIS -ACM, April 2024
AI/AN: American Indian or Alaska Native; NH/PI: Native Hawaiian or Other Pacific Islander
The April estimates are based on data collected April 1 through April 27, 2024.
CDC.COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 30, 202422 49 73
26 56 63
35 50 74
29 64 85
20 48 78
31 39 52
28 55 65
0 10 20 30 40 50 60 70 80 90 100
Very or moderately concerned about COVID-19
disease Confidence that COVID-19 vaccine is very or
completely safe Confidence that COVID-19 vaccine is somewhat
or very important to protect me Percent Hispanic
White, non-Hispanic
Black, non-Hispanic
Asian, non-Hispanic
NH/PI, non-Hispanic
AI/AN, non-Hispanic
Other or multiple races, non-Hispanic
46

  Concern about risk of COVID -19 by race and ethnicity,
February 2024
% of U.S. adults who say they are very/somewhat concerned that they…
White 5
Black
Hispanic
Asian
0 Will get COVID -19 and
require hospitalization
15
20
16 22
18 18
10 20 30
Very concerned Somewhat concerned 23
40 50 White 8
Black
Hispanic
Asian
0 Might unknowingly spread
COVID -19 to others
27
24 27
18 31
20 34
10 20 30 40 50
Very concerned Somewhat concerned 60
Survey conducted among 10,133 U.S. adults from February 7 -11, 2024.
Pew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-
coronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 47

  Concern about risk of COVID -19 by income,
February 2024
% of U.S. adults who say they are very/somewhat concerned that they…
Survey conducted among 10,133 U.S. adults from February 7 -11, 2024.
Pew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-
coronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 19 10 9
27 27 29
0 10 20 30 40 50 Lower income Middle income Upper income Might unknowingly spread
COVID -19 to others
Very concerned Somewhat concerned 17 7 5
21 16 11
0 5 10 15 20 25 30 35 40 Lower income Middle income Upper income Will get COVID -19 and
require hospitalization
Very concerned Somewhat concerned
48

  Summary
Values
• Approximately 30% of parents of children ages 6 months – 17 years reported
concern about their child getting COVID -19, but confidence in COVID -19 vaccine
safety and vaccine importance was highest among parents of adolescents
• Adults ages 65 years and older were more concerned about COVID -19 disease and
had higher confidence in vaccine safety and vaccine importance than those <65
years
• Racial and ethnic minority groups, older adults, and those with lower incomes are
more concerned about getting COVID -19 than other groups
49
o o o o o o  Minimal  Small  Moderate Large  Varies  Don’t know

  Values
Criteria 1:
Do persons ≥6 months of age feel that the desirable effects are large relative
to undesirable effects?
• How do persons ≥6 months of age view the balance of desirable versus
undesirable effects?
• Would persons ≥6 months of age feel that the benefits outweigh the
harms?

o
o
oo
o

 Values
Criteria 2:
Is there important uncertainty about, or variability in, how persons ≥6
months of age value the main outcomes?
• Is there evidence that the variability is large enough to lead to different
decisions?
Majority opinion
Minority opinion Important uncertainty or variability
Probably important uncertainty or variability
Probably not important uncertainty or variability
No important uncertainty or variability
No known undesirable outcomes
  EtR Domain:
Acceptability
Declining share of Americans have the most up -to-
date level of protection against COVID -19
% of U.S. adults who report that they are up to date with COVID -19 vaccines
80 Nov. 2021
All U.S. adults eligible for COVID -19 First booster dose Sept. 2022 vaccination 69 authorized for all eligible Bivalent vaccine is authorized 70 U.S. adults
Sept. 2023
Updated (2023 -2024) vaccines 60
are approved/authorized
48

50
40 34
2830
20
10
0
Apr '21 Aug '21 Jan '22 Mar '23 Feb '24
Survey conducted among 10,133 U.S. adults from February 7 -11, 2024.
Pew Research Center. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -
americans -view -the-coronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 53

 Percent of adults and children who received 2023 -24 COVID -19 vaccine
National Immunization Survey -Adult COVID Module (NIS -ACM) and -Child COVID Module (NIS -CCM)
September 2023 -April 2024
COVID -19 Vaccination Coverage with 2023 -24 Vaccine COVID -19 Vaccination Coverage with 2023 -24 Vaccine
Among Adults ≥18 Years, NIS-ACM Among Children 6 Months -17 Years, NIS -CCM Vaccinated with 2023 -24 COVID -19 vaccine (%) 50
40
30
20
10
0
9/30/23 10/31/23 11/30/23 12/31/23 1/31/24 2/29/24 3/31/24 4/30/24
Week end date All adults 18+
75+
65-74
50-64
40-49
30-39
18-2950
40
30
20
10
0
9/30/23 10/31/23 11/30/23 12/31/23 1/31/24 2/29/24 3/31/24 4/30/24
Week end date Vaccinated with 2023 -24 COVID -19 vaccine (%)
All children 6m-17y
12-17y
5-11y
6m-4y
https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/index.html 54
Intent to get 2024 -25 COVID -19 vaccine among adults ≥18 years of age, by
demographics,* Omnibus Surveys, May 2 -26, 2024 (N=4,276)
Definitely will get Definitely will not Probably will Probably will not Unsure
Overall (N=4,276)
Male (N=2,080)
Female (N=2,196)
Age 18-49 (N=2,146)
Age 50-64 (N=1,088)
Age 65+ (N=1,042)
hite, non-Hispanic (N=2,837)
Black, non-Hispanic (N=494)
Hispanic (N=621)
Other, non-Hispanic (N=324) 23.6 14.3

 23.3 13.2
20.6 20.9 26.0 23.9 15.4
39.2 16.9 12.3 15.5
10.8 36.3
35.6
20.9
13.5 13.9 36.1
19.6 12.4 23.2
18.6 11.9 31.7
17.1 18.0 23.4 13.7 32.6
31.9
33.3 14.4
13.1 Inco
Insured (N=3,645)
Uninsured (N=301) 25.3 22.7 21.2 20.4 13.1
16.1 20.1
15.7
14.5 16.6 15.7
13.7

 10.9
15.7
11.9
14.4 $50,000- $74,999 (N=805) Suburban (N=2,008)
Rural (N=750)
me $24,999 or less (N=512)
$25,000- $49,999 (N=775) Urban (N=1,518)
$75,000+ (N=2,184)
Northeast (N=669)
Midwest (N=1,070)
South (N=1,474)
West (N=1,063) 13.5
14.0
15.1 16.7
14.7
13.7 27.6
32.1
43.7
14.7
15.0
12.7
13.8 26.3 21.8 23.3 23.2 14.6
14.6 15.4
12.8
18.4 17.1 14.8
13.2 26.3 16.0
24.2 15.0
15.6 11.8
35.6
31.4
33.0
32.1
32.1
32.3
35.6
28.3
24.8
12.8 14.4
12.1 15.8
15.1 13.0
19.5 31.9
40.6
0 25 50 75 100
Weighted % 18.3 22.3 24.6 23.4 14.8 15.4
14.6
15.0 14.5
16.3
12.7
12.1
18.8 16.3 13.6
0 25 50 75 100
Weighted % W

          *NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting Area) codes, whereas Ipsos uses Office of Management and Budget's CBSA (Core Based Statistical Area) classification. †Insured group includes
plans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS, and "ot her".
Omnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of U.S. adults aged 18
years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents. 55
Intent to get an annual COVID -19 vaccine among adults ≥18 years of age, by
demographics,* Omnibus Surveys, May 2 -26, 2024 (N=4,270)
Overall (N=4,270)
Male (N=2,079)
Female (N=2,191)
Age 18-49 (N=2,142)
Age 50-64 (N=1,087)
Age 65+ (N=1,041)
ite, non-Hispanic (N=2,834)
lack, non-Hispanic (N=492)
Hispanic (N=620)
ther, non-Hispanic (N=324) 35.5
35.9
30.1
34.7
Urban (N=1,519)
Suburban (N=2,003)
Rural (N=748) 37.0

 36.1
25.2
0 Every year Some yea Never
34.5 23.9
34.6
34.4 23.4
24.4
24.7
35.9
55.6 28.8
21.1 41.6 I

 ncome $24,999 or less (N=508)
$25,000- $49,999 (N=776)
$50,000- $74,999 (N=805)
$75,000+ (N=2,181)
Northeast (N=669)
Midwest (N=1,068)
South (N=1,469)
West (N=1,064) 27.9
33.9
34.0
36.7 45.8
41.9
42.2
40.2 26.3
24.2
23.9
23.1
36.0
33.1
32.0
38.6 40.7
42.7
44.5
36.7 23.3
24.2
23.5
24.7
36.1
18.5 40.2
59.8 23.7
21.7 Insured (N=3,635)
Uninsured (N=302)
0 25 50 75 100
Weighted % 42.0
41.3
46.5
43.0
28.9 15.5
45.0 19.5
33.5
41.0 28.9
30.8 30.6
34.5
26.4
22.8 36.6
41.0
21.8 53.0
25 50 75 100
Weighted % Wh
B
O

          rs
*NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting Area) codes, whereas Ipsos uses Office of Management and Budget's CBSA (Core Based Statistical Area) classification. †Insured group includes
plans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS, and "ot her".
Omnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of U.S. adults aged 18
years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents. 56

  Key attitudes and experiences among parents of children 6 months -17 years,
December 2023 -National Immunization Survey -Child COVID Module (NIS -CCM)
Reason for Not Getting the COVID -19 Vaccine Among Respondents with
Unvaccinated Children Ages 6 Months -17 Years, NIS -CCM, December 2023
Concerned about side effects
COVID-19 vaccine is ineffective
Child unlikely to get very sick from COVID-19
Child unlikely to get COVID-19
Don't like needles or shots
Hard to get to vaccination site/sites not open at convenient times
COVID-19 vaccine costs too much 2 2 17 21 56 58 88
0 10 20 30 40 50 60 70 80 90 100
Percent
The December estimates are based on data collected November 26 through December 30.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed April 30, 202457

 Key attitudes and experiences among parents of children ages 6 months through 17
years, December 2023 -National Immunization Survey -Child COVID Module (NIS -CCM)
COVID -19 Vaccination Key Attitudes and Experiences by Age Group Among
Parents of Children Ages 6 Months –17 Years, NIS -ACM, December 2023
28 27 28
0 10 20 30 40 50 60 70 80 90 100
Healthcare provider recommended I get a 2023-2024 COVID-19 vaccine Percent6 months –4 years
5–11 years
12–17 years
The December estimates are based on data collected November 26 through December 30 2023.
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed May 30, 2024 58

 Key attitudes and experiences among adults 18 years and older, April 2024
National Immunization Survey-Adult COVID Module (NIS-ACM)
COVID-19 Vaccination Key Attitudes and Experiences by Age Group
Among Adults Age ≥18 Years, NIS -ACM, April 2024
100
90
80
70
60
18 - 49 years
50 50 - 64 years
65+ years 40
Healthcare provider recommended I get a 2023-2024 COVID-19 vaccine Percent
17 24 27
0 10 20 30

        The April estimates are based on data collected April 1 through April 27.
CDC.COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 30, 2024 59

 Top COVID -19 vaccination concerns and issues among
adults ≥18 years Omnibus Surveys, January 5 -29, 2024
• Among those that reported they received the 2023 -2024 COVID -19 vaccine or definitely would:
-The majority had no concerns or issues with COVID -19 vaccination
• 67% in aged 18 -59 years; 83% in aged ≥60 years
• Among those that reported that they probably would receive the 2023 -2024 COVID -19 vaccine or were unsure:
-Unknown serious side effects and too busy or kept forgetting were the most commonly reported issues for
those 18 -59 years old
-Effectiveness and unknown serious side effects were the most commonly reported issues for those ≥60 years
• Among those that reported that they probably/definitely would not get the 2023 -2024 vaccine:
-Unknown serious side effects, not enough studies, and distrust of government/pharma were the most
frequently reported concerns
Source: CDC, unpublished data
Omnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to survey a nationally representative
sample of U.S. adults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, b eliefs, and behaviors on each survey for 2 waves each month, for a combined
sample size of ~4,000 respondents. 60
 Domain Equity Question:
Is the intervention equally acceptable across all populations?

       Is the intervention equally acceptable across all
populations for children?
Among children ages 6 months – 17 years responding to the NIS -CCM during April 1 –
27, 2024:
• Vaccination coverage differed by race/ethnicity
-Coverage was highest among White, non -Hispanic children and lowest among
Black, non -Hispanic children
• Vaccination coverage was higher in urban/suburban areas compared with rural areas
• Children covered by private health insurance had higher vaccination coverage than
children who were uninsured or covered by Medicaid
• Vaccination coverage increased with increasing household income
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed May 24, 2024 62

 Is the intervention equally acceptable across all
populations for adults?
Among adults ages ≥18 years responding to the NIS -ACM during April 1 – 27, 2024:
• Vaccination coverage differed by race/ethnicity
-Coverage was highest among White, non -Hispanic adults and lowest among
American Indian/Alaska Native and Native Hawaiian/Other Pacific Islander adults
• Vaccination coverage was higher in urban/suburban areas compared with rural areas
• Adults with health insurance had significantly higher vaccination coverage than
adults without insurance
• Vaccination coverage increased with increasing household income
CDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 24, 2024 63

 Summary
Acceptability
• Vaccine coverage with at least 1 dose of 2023 -2024 COVID -19 vaccine was
approximately 20% in adults aged ≥ 18 years
-From August 2021 to February 2024, the percentage of adults who report being
up to date with COVID -19 vaccination has decreased from 69% to 28%
• Concern about side effects is the most likely reason for not being vaccinated
• Less than 30% of people report having received a healthcare provider
recommendation for the 2023 -2024 COVID -19 vaccine
• COVID -19 vaccine coverage varies by age, race and ethnicity, metropolitan statistical
area, insurance status and household income
64
o o o o o o

  Acceptability
Would recommending a dose of the 2024 – 2025 Formula COVID -19 vaccine
for persons ≥6 months of age be acceptable to key stakeholders?
• Are there key stakeholders that would not accept the distribution of
benefits and harms?
• Are there key stakeholders that would not accept the undesirable effects
in the short term for the desirable effects (benefits) in the future?
 No  Probably no  Probably yes Yes  Varies  Don’t know
Majority opinion Minority opinion
EtR Domain:
Feasibility

 Feasibility of vaccine implementation
• No substantial clinical consideration changes expected
– Supporting tools and documents from 2023 -2024 vaccine will not need to be significantly
revised or reprogrammed, but COVID -19 vaccine recommendations remain complex
• There will continue to be single dose presentations and minimum order quantities
– Moderna
• ≥6 months: manufacturer -prefilled syringes (10 -pack)
– Novavax
• ≥ 12 years: manufacturer -prefilled syringes (10 -pack)
– Pfizer -BioNTech
• ≥ 12 years: manufacturer -prefilled syringes (10 -pack)
• 5 – 11 years: single dose vial (10 -pack)
• 6 months – 4 years: 3 -dose multi -dose vial (10 -pack)
• Preparation has not changed
– Moderna and Novavax vaccines require no dilution
– Pfizer -BioNTech vaccine requires dilution for 6 month – 4 year formulation
CDC, Immunization Services Division, internal planning documents 67

   Storage and handling
• Moderna: Frozen until expiration; 30 days at refrigerator storage
• Novavax: Refrigerator storage (stable at 2 -8°C )
• Pfizer -BioNTech
– Prefilled syringes (≥12 years): Refrigerator storage (2 -8°C), never frozen
– Vials (6 months – 11 years): Ultra -cold storage until expiration; 10 weeks at
refrigerator storage; use within 12 hours of dilution
• Ultra -cold storage continues to be a challenge; most provider offices do not
have a unit
CDC, Immunization Services Division, internal planning documents 68

 Barriers to implementation
• Increasingly complex routine vaccination schedule, which includes immunization
products for three viral respiratory diseases1
– Need more storage space to store all recommended immunization products
– Increased need for education across vaccination provider types
– More opportunities for vaccine administration errors
• Financial burden for healthcare practices with costly vaccine and low demand and
for uninsured and underinsured with the end of the Bridge Access Program2
• Fewer primary care practices carry COVID -19 vaccine potentially introducing barriers
to access, particularly for those with difficulty traveling to another location
for vaccination
1. COVID -19 vaccine, Influenza vaccine, RSV vaccine, and Nirsevimab , a long -acting monoclonal antibody for RSV prevention in infants
2. https://www.cdc.gov/vaccines/programs/bridge/index.html
CDC, Immunization Services Division, internal planning documents 69
 Domain Equity Question:
Is the intervention equally feasible to implement across all populations?

  COVID -19 vaccine access
•
-
•
-Free updated COVID -19 vaccines are available to most people living in the U.S.
through their private health insurance, Medicare, and Medicaid plans
Eligible children are able to receive COVID -19 vaccines through the existing
Vaccines for Children (VFC) program
However, there are 25 -30 million adults without health insurance and additional
adults whose insurance does not cover all COVID -19 vaccination costs
Bridge Access Program1, which provides free updated COVID -19 vaccines to adults
without health insurance and adults whose health insurance does not cover all
COVID -19 vaccine costs , will end in August 2024, which will result in inequities in
vaccine access
1. https://www.cdc.gov/vaccines/programs/bridge/index.html 71

  Summary
Feasibility
• The 2024 – 2025 COVID -19 vaccine will continue to consist of single dose vial
presentations and smaller minimum order quantities
-Storage and handling requirements will remain the same as well
• The increasingly complex routine vaccination schedule, which includes
immunizations for three seasonal viral respiratory diseases, presents potential
barriers to implementation such as limited storage space due to more vaccines,
more opportunities for vaccine administration errors and the need for increased
education among vaccine providers
• Vaccines will continue to be accessible; however, the end of the temporary Bridge
Access Program will result in decreased vaccine access for underserved populations
72

    Feasibility
Is the 2024 – 2025 Formula COVID -19 vaccine feasible to implement among
persons ≥6 months of age?
• Is the 2024 – 2025 Formula COVID -19 vaccine program sustainable?
• Are there barriers that are likely to limit the feasibility of implementing the
2024 – 2025 Formula COVID -19 vaccine or require considerations when
implementing it?
• Is access to the 2024 – 2025 Formula COVID -19 vaccine an important
concern?
o o o o o  o Yes   No Probably no Probably yes  Varies Don’t know
EtR Domain:
Resource Use

   Incremental cost -effectiveness ratios, societal
perspective, per 1000 people -preliminary estimates
QALY: quality -adjusted life year 75
Domain Equity Question:
Is the intervention a reasonable and efficient allocation of resources
across all populations?

    Scenario analysis: probability of hospitalization,
ICER ($/QALY) -preliminary estimates
*Base case probability of h ospitalization: 5-11 years: 0 .000133; 12-17 years: 0.000181; 18 -49 years: 0.000443; 50 -64 years: 0.001550; 65+
years 0.007900
**Adjusted risk of hospitalization for underlying condition: chronic obstructive pulmonary disease: 0.9, history of stroke: 0 .9, coronary artery
disease: 1.3, asthma: 1.4, hypertension: 2.8, obesity: 2.9, diabetes: 3.2, chronic kidney disease: 4.0, severe obesity: 4.4. Ko et al 2021.
ICER : incremental cost-effectiveness ratio; QALY: Quality -adjusted life year
77

 Summary
Resource Use
• Base case ICERs ranged from $23,308 in adults aged ≥65 years to $212,225 in adults aged 18 -49 years
• Cost -effectiveness estimates in those ages ≥65 years were robust to input changes across plausible
ranges
• Cost -effectiveness estimates in those 18 -64 years were sensitive to changes in inputs
-ICERs are more favorable for higher vaccine impact, higher risk of hospitalization, higher quality of
life impact for symptomatic illness and lower vaccine dose cost
• Cost -effectiveness estimates for those 5 -17 years were very sensitive to changes in inputs
-ICERs are more favorable for higher vaccine impact, higher risk of hospitalization, higher quality of
life impact, higher probability of symptomatic illness and lower vaccine dose cost
• COVID -19 vaccination is most cost -effective in older adults in which disease burden is highest
compared to younger adults
• COVID -19 vaccination is likely more cost -effective in populations with risk factors, such as underlying
conditions, which increase their probability of hospitalization due to COVID -19
• ICERs would be more favorable in younger age groups if the cost of vaccination was lower
ICER: incremental cost -effectiveness ratio 78

  Resource Use
Is the 2024 – 2025 Formula COVID -19 vaccine in persons ≥6 months of age a
reasonable and efficient allocation of resources?
•
• What is the cost -effectiveness of the 2024 – 2025 Formula COVID -19
vaccine?
How does the cost -effectiveness of the 2024 – 2025 Formula COVID -19
vaccine change in response to changes in context, assumptions, etc.?
o No o o o o o Probably no  Probably yes  Yes  Varies  Don’t know
Majority opinion Minority opinion
Summary and Work Group Interpretations

 Work Group Interpretation
• COVID -19 burden is currently lower than at previous points in the pandemic, however there are still
thousands of hospitalizations and hundreds of deaths each week
• People ages 5 – 49 years had the lowest hospitalization rates compared to other age groups
-Severe outcomes occur in the youngest ages, including in children with no underlying medical
conditions
• Additional studies are needed to understand the VSD statistical signals seen for the 2023 -
2024 COVID -19 vaccine
-The increased rate of GBS following Pfizer COVID -19 vaccine among people aged ≥65 years may
or may not represent a true risk. If it is a true risk, the burden of disease in this age group
is such that the benefit of vaccination still outweighs the risk
-The VSD statistical signals for ischemic stroke after mRNA COVID -19 vaccines during the 2023 -
2024 season do not provide sufficient evidence to conclude that there is a safety concern and
a follow up VSD study is in progress
VSD: Vaccine Safety Datalink | GBS: Guillain -Barre Syndrome 81

 Work Group Interpretation (cont.)
• 2023 -2024 COVID -19 vaccine coverage was low, particularly in children
-Provider recommendation may encourage greater COVID -19 vaccine uptake
-Would be important to understand why providers are not recommending vaccine,
in addition to continuing to address inequities in vaccine access
• High vaccine cost and decreased disease burden has resulted in less
favorable ICERs for younger age groups
-The Work Group expressed concern about current ICERs for those <50 years
-The Work Group noted that while the burden of disease in pediatric age
groups supported recommending COVID -19 vaccine in these age groups, the high
cost of vaccine was a concern
-ICERs in pediatric age groups are sensitive to changes in parameter
inputs (i.e., uncertain) and are still considered preliminary
ICER: incremental cost -effectiveness ratio 82

             Work Group Interpretation:
Considerations for Universal Recommendation
• Work Group began deliberations considering both universal and non -universal policy options, but
non-universal options had significant implementation challenges
-Risk based recommendations would not allow access to COVID -19 vaccines for those not in a
defined risk group
• The current list of conditions that increase risk of severe illness due to COVID -191 is
extensive and includes the majority of the US adult population2
• There are no groups without a risk of severe illness
-Shared clinical decision (SCDM) making would create barriers to vaccination , may not effectively
target those at highest risk , and would likely increase inequities in vaccine access
-COVID -19 epidemiology remains uncertain and universal recommendations would need to be
considered if there was an unexpected increase in burden following a risk -based or SCDM decision
• COVID -19 disease burden remains substantial, and consistent recommendations may increase
coverage over time
1. https://www.cdc.gov/coronavirus/2019 -ncov/hcp/clinical -care/underlyingconditions.html
2. Overweight and obesity are considered conditions with conclusive or suggestive evidence of increasing risk and have a combine d prevalence >70%. National Health Statistics Reports;
https://stacks.cdc.gov/view/cdc/106273 83

 Summary of Work Group Interpretation
• Benefits of COVID -19 vaccination vary by age and risk status
-Under a universal recommendation, 2024 -2025 COVID -19 vaccines will be
available to all persons ages ≥6 months
-Additional implementation efforts should be targeted toward those that will
receive the most benefit from COVID -19 vaccination, including people ≥65 years 1
old, people with underlying conditions1 including immunocompromise, and
pregnant people to protect themselves and their infants
• The Work Group will continue to evaluate COVID -19 vaccine policy, including the
need for a universal recommendation, particularly as COVID -19 epidemiology
continues to change
1. https://www.cdc.gov/coronavirus/2019 -ncov/hcp/clinical -care/underlyingconditions.html 84

  EtR Domain Question Work Group Judgments
Public Health ProblemIs COVID -19 disease among persons ≥6 months of age of public health
importance? Yes
How substantial are the desirable anticipated effects? Moderate / Large
Benefits and Harms How substantial are the undesirable anticipated effects? Small
Do the desirable effects outweigh the undesirable effects? Favors intervention
Do persons ≥6 months of age feel that the desirable effects are large
relative to undesirable effects? Varies
ValuesIs there important uncertainty about, or variability in, how persons ≥6
months of age value the main outcomes? Probably important uncertainty or
variability
AcceptabilityWould recommending a dose of the 2024 -2025 Formula COVID -19
vaccine for persons ≥6 months of age be acceptable to key stakeholders? Varies
FeasibilityIs the 2024 -2025 Formula COVID -19 vaccine feasible to implement
among persons ≥6 months of age? Probably yes / Varies
Resource UseIs the 2024 -2025 Formula COVID -19 vaccine in persons ≥6 months of age
a reasonable and efficient allocation of resources? Probably yes
85

 Evidence to Recommendations Framework
Summary: Work Group Interpretations
Undesirable Undesirable The balance
between Desirable Desirable There is
Balance of
consequences consequences
clearly outweigh
desirable
consequences consequences
probably
outweigh
desirable desirable and
undesirable
consequences
is closely consequences
probably
outweigh
undesirable consequences
clearly
outweigh
undesirable insufficient
evidence to
determine the
balance of
in most settings consequences
in most settings balanced or
uncertain consequences
in most settings consequences
in most settings consequences
Minority opinion Majority opinion 86
 Evidence to Recommendations Framework
Summary: Work Group Interpretations
We recommend the
Type of We do not recommend intervention for individuals We recommend the
recommendation the intervention based on shared clinical intervention
decision -making
87
  ACIP Voting Language
ACIP recommends 2024 -2025  COVID-19 vaccines as authorized
or approved by FDA in persons ≥6 months of age
FDA: Food and Drug Administration 88

 Acknowledgements
• Megan Wallace
• Monica Godfrey
• Danielle Moulia
• Katherine Fleming -Dutra
• Ruth Link -Gelles
• Sarah Meyer
• Elisha Hall
• Jennifer Kriss
• Kayla Calhoun
• Kevin Chatham -Stephens
• Susan Goldstein
• Mary Chamberland
• JoEllen Wolicki
• Lauren Roper
• Karen Broder • Evelyn Twentyman
• Angela Campbell
• Sharon Saydah
• Matthew Oster
• Sierra Scarbrough
• Natalie Thornburg
• Jefferson Jones
• Dave Wentworth
• Aron Hall
• COVID -NET
• University of Michigan COVID -19 Vaccination Modeling Team
• Immunization Safety Office
• Immunization Services Division
• Coronavirus and other Respiratory Viruses Division
• National Center for Immunization and Respiratory Diseases
89

 Thank you
For more information, contact CDC
1-800-CDC-INFO (232 -4636)
TTY: 1 -888-232-6348  cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position
of the U.S. Centers for Disease Control and Prevention.

GRADE

         Outcomes and importance, and data sources
Outcome Importancea Data sources
Benefits
Medically -attended COVID -
19 (ED/UC visits) Critical Observational studies of vaccine effectiveness in adults/adolescents and
absolute vaccine effectiveness in pediatrics
Hospitalization due to COVID -19 Critical Observational studies of vaccine effectiveness
Death due to COVID -19 Important Observational studies of vaccine effectiveness
Post -COVID conditions Important Observational studies of vaccine effectiveness
MIS-C (pediatric only) Important Observational studies of vaccine effectiveness
Harms
Specified serious adverse events
(SAEs) (myocarditis/pericarditis
and anaphylaxis) Critical Safety surveillance for pre -specified SAEs
ED/UC: emergency department/urgent care; MIS -C: multisystem inflammatory syndrome in children;
a. Three options: Critical; Important but not critical; Not important for decision making
92
   Evidence retrieval
Records identified  from
WHO/IVAC  literature review*
(n = 310) Additional records identified  through
other sources
(n = 3)
Records screened
(n = 313)
Records assessed  for
eligibility
(n =2 0)
Records  included  in e vidence
synthesis  (n =  16)
13  vaccine effectiveness  studies
3 safety surveillance  studies Records excluded  from initial review
(n  =  293)
211  different country
31  different outcome
51  different study period
Full-text articles excluded
(n = 4)
2  different comparator
2 different study period
*See https://view -hub.org/resources ; 5/10/2024 cutoff date 93

 Evidence retrieval for vaccine effectiveness (VE) data
▪Inclusion Criteria for IVAC systematic review* ▪Additional criteria for GRADE review
– Published or preprint study with adequate – Studies relevant to PICO question components –
scientific details population, intervention, comparator, and
outcomes – Includes group with and without infection or
disease outcome – Studies set in the US
– Laboratory confirmed outcome† – Study period after September 2, 2022
– Vaccination status confirmed in ≥90% – Vaccines with updated formulation (i.e., bivalent
or 2023 -2024 vaccine) – Studies assess one vaccine or pooled COVID -19
vaccines – Included studies of general population and
special populations (e.g., elderly) – Includes participants who did or did not receive a
COVID -19 vaccine§
– Vaccine effectiveness estimate includes
confidence intervals if possible¶
Articles were eligible for inclusion if published before 5/10/24. *Criteria included in the ongoing systematic review condu cted by the International Vaccine Access Center and the World Health Organization
(see https://view -hub.org/resources ).  † Estimates of effectiveness against progression from infection disease are excluded § Comparison group is not modelled or historical ¶ Estimate accounts for
confounding or statement that adjustment had no effect on estimate 94

     Evidence retrieval
• Observational studies for benefits (vaccine effectiveness)
-Peer reviewed and preprint articles from IVAC systematic reviewa
-Restricted to PICO defined population, intervention, comparison, and outcome
• Safety surveillance for pre -specified serious adverse events for harms
-Data on established safety concerns identified by vaccine safety surveillance systems
-Based on input from CDC’s Immunization Safety Office (ISO)
aArticles were eligible for inclusion if published before 5/10/2024 95

 Observational data (n = 16)
• 16 records identified (one or more PICO outcomes)
• Assessed risk of bias using Newcastle -Ottawa Scale (9 -point scale)
-For cohort studies: Selection of cohorts, Comparability of cohorts, Assessment of
outcome
-For case -control or test -negative design studies: Selection of cases and controls,
Comparability of cases and controls, Ascertainment of exposure
• Two reviewers assessed each study for each outcome
• Serious limitations identified by score <7
96

 Pooling vaccine effectiveness estimates
• For each outcome, assessed body of evidence for suitability for pooling
-Most representative study selected if multiple studies in same population
-If the outcomes were measured at multiple timepoints, longest follow -up time
was taken
• Vaccine effectiveness comparisons included an updated dose (either
bivalent or 2023 -2024 formulation) compared to no updated dose (may
include people who received any number of doses of prior formulations and
unvaccinated, definitions varies by included study)
• Meta -analyses conducted
• Estimates evaluated for heterogeneity
• Resulting pooled estimates summarize real -world data available at time of
GRADE analysis
97

 Determining the GRADE certainty assessment
▪Initial evidence type (certainty level) determined by study design
– Initial evidence high certainty : A body of evidence from randomized controlled
trials
– Initial evidence low certainty : A body of evidence from observational studies
▪Evidence type may be downgraded due to risk of bias, inconsistency, indirectness,
and imprecision. Evidence type may be upgraded or downgraded due to other
considerations including publication bias or indications of dose -response gradient,
large or very large magnitude of effect, and opposing residual confounding.
▪Final evidence type may range from high certainty to very low certainty
98
Adolescents and adults

    Benefits: Studies included for VE against medically -attended COVID -19 (ED/UC visits)
Study Population
(age group) Method Time period Median days
since updated
dose Comparison n/N  or n
cases/N
total cases n/N or n
controls/N
total controls Vaccine
Effectiveness
(95% CI) Included in
pooled estimate?
(reason if no)
Tsenga
June 3, 2023
(Manufacturer
funded) General population
(6+ yr old
immunocompetent &
immunocompromised) Retrospective cohort
– matched 8/31/2022 – 12/31/2022
(18+ yr old)
10/12/2022 -12/31/2022
(6 -17 yr old) 74 days BV
vs 2 doses OMV 855/290292 2083/580584 55 (51 – 59) No – overlapping
study population
Tenforde
December 16,
2022b General population
(18+ yr old
immunocompetent) Test -negative 9/12/2022 – 11/18/2022 25 days BV mRNA vs
2 doses OMV 338/2738 4359/20361 50 (44 -56) Yes
Tartof
October 5,
2023
(Manufacturer
funded) General population
(18+ yr old
immunocompetent &
immunocompromised Test -negative 8/31/2022 -4/15/2023 77 days Pfizer BV compared
to at least two doses
OMV 10249 cases 53317 controls 35 (30 -40) Yes
Ackerson
April 4, 2024
(Manufacturer
funded) General population
(18+ yr old
immunocompetent &
immunocompromised) Test -negative 9/1/2022 – 6/30/2023 Half of
BA.4/BA.5 14 -60
days Moderna BV
compared to at least
two OMV BA.4/BA.5:
218/1930 BA.4/BA.5:
1190/5254 BA.4/BA.5: 58
(50 – 65) Yes
Half of XBB 60 -
180 days XBB:
343/1307 XBB:
1113/3837 XBB:
26 (13 – 36)
DeCuir
February 29,
2024 General population
(18+ yr old
immunocompetent) Test -negative 9/25/2023 -1/9/2024 44 days 2023 -2024 dose
compared to no
updated dose 1297/17229 13378/111596 47 (44 -50) Yes
Caffrey April
7, 2024a
(Manufacturer
funded) VA beneficiaries
(immunocompetent &
immunocompromised) Test negative 1/25/2024 -1/31/2024 76 days 2023 -2024 dose
Pfizer compared to
no updated dose Cases and controls: 61976 39 (33 -45) Yes
ED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval; BV: bivalent; OMV: original mono valent
a. Pre-print article
b. Reprint date March 17, 2023 100

     Benefits: Sensitivity analyses for VE against medically -
attended COVID -19 (ED/UC visits)
Sensitivity analysis Number of studies VE (95% CI)
Overall estimate 5 43 (30, 54)
Published studies only 4 44 (27, 57)
Non -manufacturer -funded studies only 2 48 (30, 61)
Bivalent dose studies only 3 43 (16, 62)
2023 -2024 dose studies only 2 45 (42, 47)
ED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval
101

          -Benefits: Evidence table for VE against m edically -
attended COVID -19 (ED/UC visits)
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Updated
COVID 19
vaccine No updated
vaccine Vaccine
Effectiveness
(95% CI)
5a Obsb,c not
seriousd not serious not seriouse not serious none 27478 cases/190528 controls
61976 cases and controls 43
(30 to 54)f Low CRITICAL
ED/UC: emergency department/urgent care ; VE: vaccine effectiveness; CI: confidence interval
a. Six studies were available in the body of evidence. One excluded because the study population was already represented.
b. The body of evidence includes preprints
c. The body of evidence includes manufacturer -funded studies
d. Two studies contained data only for Pfizer COVID -19 vaccine and one study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial
risk bias in the magnitude of effect.
e. Although I2 value was high (90%), no serious concern for inconsistency was present because all studies showed consistent magnitudes of ef fect at similar time points post updated
dose
f. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale.
102
   Benefits: Certainty assessment for VE against
medically -attended COVID -19 (ED/UC visits)
▪Observational Studies (n=5)
▪Pooled vaccine effectiveness 43% (95% CI: 30 to 54)
▪No serious concerns in certainty assessment.
▪Final certainty assessment: Low certainty
ED/UC: emergency department/urgent care; CI: confidence interval 103

  Benefits: Cohort studies included for VE against
hospitalization due to COVID -19
Study Population
(age group) Method Time period Median days
since
updated
dose Comparison n/N n/N VE (95% CI) Included in pooled
estimate?
(reason if no)
Lin February
23, 2023 General population
(12+ yr old
immunocompetent &
immunocompromised) Retrospective
cohort 9/1/2022 – 12/8/2022 - BV
vs
2 doses OMV - -59 (44 – 70) No
(study population
overlapped with another
study)
Lin
May 11, 2023 General population
(12+ yr old
immunocompetent &
immunocompromised) Retrospective
cohort 9/1/2022 – 2/10/2023 Maximum: 105
days BV
vs
2 dose OMV 253/127982 1955/50265509 40 (26 – 51) Yes
Tseng
June 3, 2023a,
b General population
(6+ yr old
immunocompetent &
immunocompromised) Retrospective
cohort –
matched 8/31/2022 – 12/31/2022
(18+)
10/12/2022 -12/31/2022
(6-17 yr old) 74 days Moderna BV
vs
2 dose OMV 160/290292 646/580584 70 (64 – 75) No (study population
overlapped with another
study)
Paritala
December 4,
2023 General population
(12+ yr old
immunocompetent &
immunocompromised) Retrospective
cohort 9/1/2022 Maximum: 200
days BV compared
vs 1 fewer
dose 371/215576 1009/539191 22 (0 – 49) Yes
VE: vaccine effectiveness; CI: confidence intervals; BV: bivalent; OMV: original monovalent
a. Pre-print article
b. Manufacturer funded study
104

     Benefits: Case control studies included for VE against hospitalization due to COVID -19
Study Population
(age group) Method Time period
(predominant
variant) Median time
since
updated dose Comparison Vaccinated
cases, no./total
no. Vaccinated
controls
no/total no. VE (95% CI) Included in pooled
estimate?
(reason if no)
Surie
May 26, 2023a General population
(65+ yr old immunocompetent) Test -negative 9/8/2023 – 4/1/2023 34 days BV (7 -59 days earlier)
vs 2 OMV 61/844 175/1059 60 (45 – 71)
No (overlapping with another
study) 89 days BV (60 -119 days
earlier) vs 2 OMV 105/888 183/1067 35 (14 – 51)
141 days BV (120 -176 days
earlier) vs 2 OMV 73/856 92/976 17 (-21 – 42)
Tenforde
Dec 16, 2022b General population
(18+ yr old immunocompetent) Test -negative 9/13/2022 -11/18/2022 23 days BV
vs
2 dose OMV 56/500 444/4933 48 (30 – 62) No (overlapping with another
study)
Link-Gelles
May 26, 2023 General population (18+ yr old
immunocompetent) Test -negative 9/13/2022 -4/21/2023 34 days BV (7 -59 days earlier)
vs 2 OMV 327/4315 4530/37811 62 (57 – 67)c
Yes 87 days BV (60 -119 days
earlier) vs 2 OMV 486/4474 4705/37986 47 (41 – 53) c
144 days BV (120 -176 days
earlier) vs 2 OMV 315/4303 4303/36276 24 (12 – 33) c
Tartof
Oct 5, 2023c General population
(18+ yr old immunocompetent
& immunocompromised) Test -negative 8/31/2022 -4/15/2023 77 days Pfizer BV vs ≥ 2
mRNA OMV 169/1457 1905/11101 39 (28 -49) Yes
Ackerson
April 4, 2024c General population
(18+ yr old immunocompetent
& immunocompromised) Test -negative 9/1/2022 – 6/30/2023 Half of
BA.4/BA.5 14 -60
days Moderna BV vs ≥ 2
mRNA OMV BA.4/BA.5: 24/235 BA.4/BA.5:
196/581 BA.4/BA.5: 67 (44 –
81) Yes
Half of XBB 60 -
180 days XBB: 40/172 XBB: 209/427 XBB: 60 (37 – 75)
DeCuir January
9,2024 General population
(18+ yr old immunocompetent) Test -negative 9/8/2022 -8/31/2023 53  days BV mRNA (7 -89 days
after) vs 2 OMV 184/1995 463/2843 48 (36 – 57)
Yes
133 days BV mRNA (90 -179
days after)
vs 2 OMV 269/2080 376/2756 17 (-1 – 31)
DeCuir ,
February 29,
2024 General population
(18+ yr old immunocompetent) Test -negative 9/21/2023 -1/9/2024 42 days
2023 -2024  dose vs
no updated dose 395/4589 4199/32914 52 (47 – 57)
Yes
Test -negative 9/21/2023 -1/31/2024 47 days 94/1194 353/2923 43 (27 – 56)
Caffrey
April 7, 2024c VA Beneficiaries (18+ yr old
immunocompetent &
immunocompromised) Test negative 1/25/2024 -1/31/2024 76 days 2023 -2024 Pfizer
dose vs no updated
dose Cases and controls: 24206 43 (34 – 51) Yes
VE: vaccine effectiveness; CI: confidence interval; BV: bivalent; OMV: original monovalent
a. Updated analysis from April 19, 2023 ACIP meeting “COVID -19 vaccine effectiveness updates” b. Reprint date March 17, 2023 c . Manufacturer funded study 105

   Benefits: Sensitivity analyses for VE against
hospitalization due to COVID -19
Sensitivity analysis Number of studies VE (95% CI)
Overall estimate 8 43 (34, 52)
Published studies only 5 48 (37, 57)
Non -manufacturer -funded studies only 5 44 (33, 53)
Test negative design studies only 6 46 (35, 54)
Bivalent dose studies only 6 43 (31, 53)
2023 -2024 dose studies only 2 47 (32, 59)
VE: vaccine effectiveness; CI: confidence interval
106

          -Benefits: Evidence table for VE against hospitalization
due to COVID -19
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Updated COVID 19
vaccine No
updated
vaccine Vaccine
Effectiveness
(95% CI)
8a Obsb,c not
seriousd not seriouse not serious not serious none 24878 cases 166023 controls
24206 cases and controls 44
(34 to 52)g Low CRITICAL
642/343558 exposed
2964/50504700 unexposedf
VE: vaccine effectiveness; CI: confidence interval
a. Six studies were available in the body of evidence. Two were excluded because the study population was already represented.
b. The body of evidence includes preprints.
c. The body of evidence includes a manufacturer -funded study.
d. Two studies contained data only for Pfizer mRNA COVID vaccine and one study contained data only for mRNA Moderna vaccine. Thi s was deemed unlikely to lead to a substantial
risk bias in the magnitude of effect.
e. Although I2 value was high ( 87%), no serious concern for inconsistency was present because all studies showed consistent magnitudes of effect at similar ti me points post bivalent
dose.
f. Measurement of outcomes differed by study (COVID -19 was not necessarily confirmed as the cause of hospitalizations), but this wa s deemed not serious.
g. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale.
107
  Benefits: Certainty assessment for VE against
hospitalization due to COVID -19
▪Observational Studies (n=8)
▪Pooled relative vaccine effectiveness 44% (95% CI: 34 to 52)
▪No serious concerns in certainty assessment.
▪Final certainty assessment: Low certainty
CI: confidence interval 108

  Benefits: Studies included for VE against death due to
COVID -19
Study Population (Age
group) Method Time period (predominant
variant) Median days
since
updated
dose Comparison n/N n/N Vaccine
Effectiveness
(95% CI) Included in pooled
estimate?
(reason if no)
Tsenga, b
June 3,
2023 General population
(6+ yr old
immunocompetent &
immunocompromised) Retrospective
cohort – matched 8/31/2022 – 12/31/2022 (18+)
10/12/2022 -12/31/2022
(6-17 yr old) 74 days Moderna BV
vs
2 dose OMV 10/290292 59/580584 82 (63 – 91) No (overlap with
another study)
Lin
May 11,
2023 General population
(12+ yr old
immunocompetent &
immunocompromised) Retrospective
cohort 9/1/2022 – 2/10/2023 Maximum: 105
days BV
vs
2 dose OMV 79/1279802 788/5026509 44 (9 – 65) Yes
Paritala , General population Retrospective 9/1/2022 – 6/15/2023 Maximum: BV vs 1 fewer dose 59/215576 167/539191 18 (0 -56) Yes
December (12+ yr old cohort 112 days
4, 2023 immunocompetent &
immunocompromised)
Ackerson
April 4,
2024b General population
(18+ yr old
immunocompetent &
immunocompromised) Test -negative 9/1/2022 – 6/30/2023 Half of
BA.4/BA.5 14 -
60 days Moderna BV
compared vs at
least two OMV BA.4/BA.5: 2/15 BA.4/BA.5:
13/38 BA.4/BA.5: 53 (-
84 – 97) Yes
Half of XBB 60 -
180 days XBB: 4/10 XBB: 17/25 XBB: 32 ( -84 –
94)
VE: vaccine effectiveness; CI: confidence intervals; BV: bivalent; OMV: original monovalent
a. Pre-print article
b. Manufacturer funded study
109

   Benefits: Sensitivity analyses for VE against death due
to COVID -19
Sensitivity analysis Number of studies rVE (95% CI)
Overall estimate 3 23 (8, 36)
Published studies only 2 43 (23, 57)
Non -manufacturer -funded studies only 2 22 (7, 35)
VE: vaccine effectiveness; CI: confidence interval
110

  -Benefits: Evidence table for VE against death due to
COVID -19
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Updated COVID 19
vaccine No
updated
vaccine Vaccine
effectiveness
(95% CI)
3 Obsa,b not not serious not serious not serious none 1130/343558 exposed 23 Low IMPORTANT
seriousc 955/50504700 unexposed (8 to 36)d
35 cases/63 controls
VE: vaccine effectiveness; CI: confidence interval
a. The body of evidence includes a preprint.
b. The body of evidence includes a manufacturer -funded study.
c. One study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial risk bias in the m agnitude of effect.
d. Pooled VE based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. Fixed effects m odel was used for this analysis due to imprecision of
the between -studies variance estimate.
111
  Benefits: Certainty assessment for VE against death
due to COVID -19
▪Observational Studies (n=3)
▪Pooled relative vaccine effectiveness was 23% (95% CI: 8 to 36)
▪No serious concerns in certainty assessment.
▪Final certainty assessment: Low
CI: Confidence interval 112
   Benefits: VE against post -COVID conditions
• No data captured in systematic review
• Common reasons for exclusion
-Review article
-Self-reported vaccination status
-Combines vaccine platforms
-Not a VE study
-Vaccination as a therapeutic (after infection)
-Different intervention (original monovalent series)
• Data not captured in the systematic review indicate that COVID vaccine provides some
protection against post -COVID conditions
113

 Harms: Safety surveillance studies included for
specified serious adverse events
▪Myocarditis/pericarditis: An analysis from the Vaccine Safety Datalink (VSD) evaluated
chart -reviewed cases of myocarditis and pericarditis occurring among adolescents and
adults aged 12 -39 years following an original monovalent booster dose and a bivalent
booster dose based on events occurring in a 7 -day risk interval after vaccination vs. a
comparison interval in vaccinated individuals.
▪Anaphylaxis: An analysis from VSD evaluated chart -reviewed cases of anaphylaxis among
all vaccinated after the original monovalent primary series persons aged 12 and older.
114

   Harms: Incidence of myocarditis/pericarditis
Incidence Rate of Verified Myocarditis/Pericarditis in the 0 to 7 Days After mRNA COVID -19 Vaccination among Persons Aged 12 – 39 Y ears by
Product, Age Group, Sex.
Original Monovalent Booster Dose Bivalent Booster Dose
Age group Cases/Doses
Administered Incidence Rate/Million Doses
(95% CI) Cases/Doses
Administered Incidence Rate/Million Doses (95% CI)
Pfizer
Male
12-17 y - - 0/55649 0.0 (0.0 – 53.8)
12-15 y 5/81613 61.3 (19.9 – 143.0) - -
16-17 y 9/47874 188.0 (86.0 – 356.9) - -
18-29 y 7/166973 41.9 (16.9 – 86.4) 1/60338 16.6 (0.4 – 92.3)
30-39 y 3/197554 15.2 (3.1 – 44.4) 0/97171 0.0 (0.0 – 30.8)
Female
12-17 y - - 0/57776 0.0 (0.0 – 51.9)
12-15 y 0/84114 0.0 (0.0 – 35.6) - -
16-17 y 2/55004 36.4 (4.4 – 131.3) - -
18-29 y 1/240226 4.2 (0.1 – 23.2) 0/95162 0.0 (0.0 – 31.5)
30-39 y 1/268412 3.7 (0.1 – 20.8) 0/133305 0.0 (0.0 – 22.5)
Moderna
Male
18-29 y 7/109337 64.0 (25.7 – 131.9) 0/22247 0.0 (0.0 – 134.7)
30-39 y 1/149468 6.7 (0.2 – 37.3) 1/41820 23.9 (0.6 – 133.2)
Female
18-29 y 1/156707 6.4 (0.2 – 35.6) 0/35393 0.0 (0.0 – 84.6)
30-39 y 2/191765 10.4 (1.3 – 37.7) 0/55816 0.0 (0.0 – 53.7)
* Primary series and monovalent booster data through August 20, 2022; 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. Bivalent booster data through March 11, 2023. Data unpublished. 115

      Harms: Incidence of anaphylaxis
• Among persons 12 and older, based on events occurring in a 0 -1 day risk
interval after either dose of primary series vaccination, the estimated
incidence of confirmed anaphylaxis among adolescents and adults was
4.8 (95% CI 3.2 -6.9) per million doses of original monovalent Pfizer -
BioNTech vaccine and 5.1 (95% CI: 3.3 -7.4) per million doses of original
monovalent Moderna vaccine. 1
-There were fewer cases of anaphylaxis post dose 2 compared with
dose 1.
CI: confidence interval
1. Klein et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399 116
Harms: Certainty assessment for specified serious
adverse events
▪Observational Studies (n=2)
▪Two rare, specified serious adverse events have been associated with
vaccination through safety surveillance
▪No serious concerns in certainty assessment.
▪Final certainty assessment: Low certainty
117
Infants and children

      -Benefits: Studies included for VE against medically -
attended COVID -19 (ED/UC visits)
Study Population
(age group) Method Time period Median
follow up
time Comparison n cases/N
total cases n controls/N
total controls Vaccine
effectiveness
(95% CI) Included in
pooled
estimate?
(reason if no)
Link-Gelles
August
2023 General population
(6 mo -5 years
immunocompetent) Test -negative
(VISION) 12/24/2022 – 6/17/2023 58 days BV
compared to
unvaccinated 3/1331 315/29133 80 (42 -96) Yes
ED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval; BV: bivalent
119

    -Benefits: Evidence table for VE against medically -
attended COVID -19 (ED/UC visits)
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Updated COVID
19 vaccine No updated
vaccine Vaccine
Eefectiveness
(95% CI)
1 Obs not
serious not serious not seriousa not serious none 1331 cases /29133 controls 80
(42 to 96) Low CRITICAL
ED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval
a. Study population only included children aged 6 months – 5 years. This was deemed insufficient to downgrade for indirectness.
120
     Benefits: Certainty assessment for VE against
medically -attended COVID -19 (ED/UC visits)
▪Observational Studies (n=1)
▪Absolute vaccine effectiveness 80% (95% CI: 42 to 96)
▪No serious concerns in certainty assessment.
▪Final certainty assessment: Low certainty
ED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval 121

   Benefits: Studies included and certainty assessment for
VE against hospitalization and death due to COVID -19
No pediatric studies captured in the evidence review on the benefits of updated COVID -
19 vaccine against hospitalization and death, however indirect evidence of adolescent
and adult benefit can be used to make inferences regarding pediatric benefit
Adolescent and adult Pediatrics (with indirectness
downgrade)
Outcome Design
(# of studies) Vaccine effectiveness
(95% CI) Final certainty assessment Final certainty assessment
Hospitalization due to COVID -
19OBS (8) 44 (34 -52) Low Very low
Death due to COVID -19 OBS (3) 23 (8 -36) Low Very low
VE: vaccine effectiveness; CI: confidence interval
122

          -Benefits: Evidence table for VE against hospitalization
due to COVID -19
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Updated COVID 19
vaccine No
updated
vaccine Vaccine
effectiveness
(95% CI)
8a Obsb,c not
seriousd not seriouse seriousf not serious none 24,878 cases 166,023 controls
24,206 cases and controls 44
(34 to 0.52)h Very Low CRITICAL
642/343,558 exposed
2,964/50,504,700 unexposedg
VE: vaccine effectiveness; CI: confidence interval
a. Six studies were available in the body of evidence. Two were excluded because the study population was already represented.
b. The body of evidence includes preprints.
c. The body of evidence includes a manufacturer -funded study.
d. Two studies contained data only for Pfizer COVID -19 vaccine and one study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial
risk bias in the magnitude of effect.
e. Although I2 value was high ( 87%), no serious concern for inconsistency was present because all studies showed consistent magnitudes of effect at similar ti me points post bivalent
dose
f. Serious concern for indirectness was present. The vast majority of the body of evidence contained data from adolescents and a dults.
g. Measurement of outcomes differed by study (COVID -19 was not necessarily confirmed as the cause of hospitalizations), but this wa s deemed not serious.
h. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale.
123

   -Benefits: Evidence table for VE against death due to
COVID -19
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerations Updated COVID 19
vaccine No
updated
vaccine Vaccine
Effectiveness
(95% CI)
3 Obsa,b not not serious seriousd not serious none 1130/343,558 exposed 23 Very Low Important
seriousc 955/50,504,700 unexposed (8 to 36)e
35 cases/63 controls
VE: vaccine effectiveness; CI: confidence interval
a. The body of evidence includes preprints.
b. The body of evidence includes a manufacturer -funded study.
c. One study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial risk bias in the m agnitude of effect
d. Serious concern for indirectness was present. The vast majority of the body of evidence contained data from adolescents and a dults.
e. Pooled VE based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. Fixed effects m odel was used for this analysis due to imprecise estimates of the
between -studies variance
124

   Benefits: VE against post -COVID conditions and MIS -C
• No data captured in systematic review
• Common reasons for exclusion
-Review article
-Self-reported vaccination status
-Combines vaccine platforms
-Not a VE study
-Vaccination as a therapeutic (after infection)
-Different intervention (original monovalent series)
• Data not captured in the systematic review indicate that COVID vaccine
provides some protection against post -COVID conditions and MIS -C
MIS-C: multisystem inflammatory syndrome in children 125

 Harms: Safety surveillance studies included for
specified serious adverse events
▪Myocarditis/Pericarditis: An analysis from the Vaccine Safety Datalink (VSD)
among children aged 5 -11. Rates are following an original monovalent booster
dose.
▪Anaphylaxis: An analysis from VSD among adolescents and adults ages 12 and
older. Rates are following primary series doses.
126

 Harms: Incidence of myocarditis/pericarditis
▪A single, observational study from the Vaccine Safety Datalink (VSD) evaluated chart -reviewed cases of
myocarditis occurring among children aged 5 -11 years following an original monovalent booster based on
events occurring in a 7 -day risk interval after vaccination vs. a comparison interval in vaccinated individuals.
▪Data from VSD and the Vaccine Adverse Events Reporting System (VAERS) do not suggest an increased risk
in children aged 6 months – 4 years
Table. Incidence Rate of Verified Myocarditis/Pericarditis in
the 0 to 7 Days After mRNA COVID -19 Vaccination among
Persons Aged 5 -11 Y ears by Age Group and Sex.
Age
group Cases/Original
Monovalent Booster
Doses Administered Incidence Rate/Million Doses
(95% CI)
Pfizer
Male
5-11 y 0/50415 0.0 (0.0 -59.4)
Female
5-11 y 0/49261 0.0 (0.0 -60.8)
1. Goddard et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the Unite d States. Annals
of Internal Medicine. https://www.acpjournals.org/doi/10.7326/M22 -2274 127

 Harms: Incidence of anaphylaxis
• Risk of anaphylaxis in children can be indirectly inferred from the known
risk in persons ages 12 and older1
-4.8 (95% CI: 3.2 -6.9) per million doses of original monovalent Pfizer -BioNTech
-5.1 (95% CI: 3.3 -7.4) per million doses of original monovalent Moderna
• There were fewer cases of anaphylaxis post dose 2 compared with dose 1.
1. Klein et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399
128

  Harms: Evidence table for serious adverse events
(myocarditis and anaphylaxis)
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerati
ons Intervention Comparison Relative
(95% CI)
1 Obs not not serious seriousa not serious None • An analysis from Vaccine Safety Datalink (VSD) evaluated chart -reviewed cases Very Low CRITICAL
serious of myocarditis occurring among children aged 5 –11 years following a bivalent
dose. Based on events occurring in a 7 -day risk interval after vaccination vs. a
comparison interval in vaccinated individuals. Among children aged 5 -11
years who received an updated dose of Pfizer -BioNTech, there 0 cases of
myocarditis among 50,415 males and 0 cases among 49,261 females (rate per
million doses in men was 0 [95% CI: 0 -59.4] and women was 0 [95% CI: 0 -
60.8])
• A rapid cycle analysis of data from VSD evaluated chart -reviewed cases of
anaphylaxis among all vaccinated persons aged 12 and older. Based on events
occurring in a 0 -1 day risk interval after vaccination, the estimated incidence
of confirmed anaphylaxis among adolescents and adults 4.8 (95% CI 3.2 -6.9)
per million doses of BNT162B2 and 5.1 (95% CI: 3.3 -7.4) per million doses of
mRNA -1273. There were fewer cases of anaphylaxis post dose 2 compared
with dose 1.b
a. Serious concern for indirectness, as the body of evidence for myocarditis was only among children aged 5 -11 receiving a monovale nt booster and the body of evidence for anaphylaxis was among
adults and adolescents aged 12 years and older receiving a primary series
b. Among children ages 5 -11, the Vaccine Adverse Events Reporting System (VAERS) had 6 reports of anaphylaxis (reporting rate of 0. 4 per million doses administered) from November 3rd 2021 –
February 7th 2022. Among children ages 6 mo – 5 years, VAERS had 1 report of anaphylaxis from June 18 – August 21, 2022. 129

  Harms: Certainty assessment for specified serious
adverse events
▪Observational Studies (n=2)
▪Two specific, rare SAE has been associated with vaccination through safety
surveillance
▪Serious concern for indirectness, as the body of evidence for myocarditis was for
an original monovalent booster and the body of evidence for anaphylaxis was
among adults and adolescents aged 12 years and older receiving a primary
series
▪Final certainty assessment: Very low certainty
CI: Confidence interval; RR: Risk ratio 130

        -Harms: Evidence table for serious adverse events
(myocarditis and anaphylaxis)
Certainty assessment № of patients Effect
Certainty Importance № of
studies Study
design Risk of
bias Inconsistency Indirectness Imprecision Other
considerati
ons Updated COVID 19 vaccine Comparison Relative
(95% CI)
1 Obs not
serious not serious not seriousa not serious None • An analysis from Vaccine Safety Datalink (VSD) evaluated chart -reviewed cases of myocarditis occurring
among persons aged 12 –39 years following an original monovalent booster dose and a bivalent dose. Based
on events occurring in a 7 -day risk interval after vaccination vs. a comparison interval in vaccinated
individuals. Among adolescents aged 12 --17 years who received a bivalent booster dose of Pfizer -
BioNTech, there 0 cases of myocarditis among 55,549 males and 0 cases among 57,776 females (rate per
million doses in men was 0 [95% CI: 0 -5] and women was 0 [95% CI: 0 -52]). Among adults aged 18 – 49 years
there were 2 myocarditis cases in 221,576 males, and 0 in 319,676 females. Among Pfizer -BioNTech
recipients, rates per million doses were: 17 (95% CI: 1 –92) in males ages 18 –29 years; 0 (95% CI: 0 –32) in
females ages 18 –29 years; 0 (95% CI: 0 –31) in males ages 30 –39 years and 0 (95% CI: 0 –23) in females ages
30–39 years. Among Moderna recipients, rates per million doses were: 0 (95% CI: 0 –135) in males ages 18 –
29 years; 0 (95% CI: 0 –85) in females ages 18 –29 years; 24 (95% CI: 1 –133) in males ages 30 –39 years and 0
(95% CI: 0 –54) in females ages 30 –39 years. Among adolescents ages 12 -15 years who received an original
monovalent booster dose of Pfizer -BioNTech, there were 5 cases of myocarditis among 81,613 males and 0
cases among 84,114 females (rate per million doses in males was 61 [95% CI: 20 – 143] and in females was 0
[95% CI: 0 --36]). Among adolescents ages 16 -17 years, there were 9 cases of myocarditis among 47,874
males and 2 cases among 55,004 females (rate per million doses in males was 188 [95% CI: 86 – 357] and in
females was 36 [95% CI: 4 -131]) Among adults ages 18 -29 years, there were 7 cases of myocarditis among
166,973 males and 1 case among 240,226 females (rate per million doses in males was 42 [95% CI: 17 – 86]
and in females was 4 [95% CI: 0 -23). Among adults ages 30 -39 years, there were 3 case of myocarditis
among 197,554 males and 1 case among 268,412 females (rate per million doses in males was 15 [95% CI: 3
– 44] and in females was 4 [95% CI: 0 -23). Among adults ages 18 -29 years who received an original
monovalent booster dose of Moderna, there were 7 cases of myocarditis among 109,337 males and 1 case
among 156,707 females (rate per million doses in males was 64 [95% CI: 26 – 132] and in females was 6
[95% CI: 0 – 36]). Among adults ages 30 -39 years, there was 1 case of myocarditis among 149,468 males and
2 cases among 191,765 females (rate per million doses in males was 7 [95% CI: 0 – 37] and in females was
10 [95% CI: 1 -38).
• An analysis of data from VSD evaluated chart -reviewed cases of anaphylaxis among all vaccinated persons
aged 12 and older. Based on events occurring in a 0 -1 day risk interval after vaccination, the estimated
incidence of confirmed anaphylaxis among adolescents and adults 4.8 (95% CI 3.2 -6.9) per million doses of
BNT162B2 and 5.1 (95% CI: 3.3 -7.4) per million doses of mRNA -1273. There were fewer cases of anaphylaxis
post dose 2 compared with dose 1. Low CRITICAL
a. Indirectness was noted for anaphylaxis, as rates were from the primary series. Primary series rates of anaphylaxis are likely an overestimate of the rate in the current phase of COVID -19
after an updated vaccine, and this was deemed not serious. 131

Summary: National Center  for Immunization and Respiratory Diseases  Evidence to Recommendations Framework:  2024 -2025 COVID -19 Vaccines in Persons ≥6 Months of Age  Lakshmi Panagiotakopoulos, MD, MPH  ACIP Meeting  June 27, 2024             Evidence to Recommendations (EtR) Framework  Policy Question  • Should 2024 – 2025 COVID -19 vaccines be recommended for use in persons  ≥6 months of age?  • Products and ages under review for authorization or approval by FDA  include:  -Moderna COVID -19 vaccine…