COVID 04 Talbot 508

COVID-19 Vaccine Safety Technical (VaST)
Work Group
VaST assessment
H. Keipp Talbot, MD MPH (VaST Chair)
Robert H. Hopkins, Jr., MD (NVAC Chair )
Advisory Committee on Immunization Practices
February 24, 2023
COVID -19 Vaccine Safety Technical (VaST) Work Group
Objectives
Review, evaluate, and interpret post -a uthorization/approval COVID -19
vaccination safety data
Serve as the central hub for technical subject matter expertise from
fe
deral agencies conducting post-authorization/approval safety
monitoring
Advise on analyses, interpretation, and presentation of vaccine safety data
Provide updates to the ACIP COVID -19 Vaccines Work Group and the
entire ACIP on COVID -19 vaccine safety
2
Activities
From December 21, 2020 through February 24, 2023
–
––71 independent meetings to review vaccine safety data17 joint meetings with ACIP COVID-19 Vaccines Work Group22 ACIP meeting presentations or reports with VaST assessments
3COVID -19 Vaccine Safety Technical (VaST) Work Group
VaST assessment
Statistical signal for ischemic stroke in the Vaccine Safety Datalink
fo
llowing bivalent COVID -19 booster vaccination
Myocarditis/pericarditis following mRNA COVID-19 vaccination
4
The statistical signal among persons aged ≥ 65 years for ischemic stroke/transient
is
chemic attack (TIA) following bivalent Pfizer-BioNTech COVID -19 booster vaccination
in VSD is based on limited data and has been attenuating over time.
A signal has not been observed in two other U.S. active vaccine safety monitoring sy
stems1, nor in data from other countries2.
–The U.S. systems differ from each other; the VSD and VA analyses included TIA w
ith ischemic stroke, while FDA CMS analysis did not.
–VSD is the only U.S. system that uses concurrent comparator groups .
–The VA and FDA CMS analyses have not evaluated simultaneous administration w
ith influenza vaccination.
5VaST assessment –statistical signal for ischemic
stroke/TIA in the Vaccine Safety Datalink (VSD)
1FDA analysis of Centers for Medicare and Medicaid Services (CMS) data, and Department of Veterans Affairs (VA) rapid cycle an alyses
2Israel and European countries
No increased rate ratio for ischemic stroke/TIA following bivalent Moderna COVID -19
booster vaccination .
Previous surveillance in VSD and other U.S. systems found no evidence of increased
risk of ischemic stroke/TIA after the primary series or monovalent COVID -19 booster
vaccination for either Pfizer- BioNTech or Moderna products.
6VaST assessment –statistical signal for ischemic
stroke/TIA in the Vaccine Safety Datalink (VSD)
The cause of the increased rate ratio is unclear; potential contributing factors include
s
imultaneous administration of bivalent COVID -19 booster and influenza vaccines* or
unmeasured confounding or bias.
VaST would like to review additional data on simultaneous administration of bivalent C
OVID -19 booster and influenza vaccination.
VaST highlighted several areas for further exploration:
–
–Assess the impact of recent respiratory viral illness (e.g., COVID -1 9, influenza) on
risk of ischemic stroke/TIA.
Analyses in VSD h ighlighted potential reasons for the lower rate of ischemic
stroke/TIA in the vaccinated comparator group, which could be contributing to the
increased rate ratio. These should be explored further.
7VaST assessment –statistical signal for ischemic
stroke/TIA in the Vaccine Safety Datalink (VSD)
*Most VSD participants aged≥ 65 years received high- dose influenza vaccine in 2022 -23 season
VaST has reviewed data on myocarditis/pericarditis following COVID -1 9 vaccination
since April 2021 and provided several assessments at ACIP meetings.
–
–
–
–Rates a fter the monovalent primary series, monovalent booster doses and
bivalent booster doses have been assessed.
Rates h ighest in adolescent and young adult males following primary series
dose 2 and first monovalent booster dose.
Outcomes after the monovalent primary series and monovalent booster doses
h
ave also been assessed.
Data on rates after bivalent COVID- 1 9 booster vaccination are limited.
Current data in VSD do not raise additional concerns about myocarditis f
ollowing bivalent COVID -19 booster vaccination.
8VaST assessment –myocarditis/pericarditis following
mRNA COVID-19 vaccination
The ACIP COVID -19 Vaccines Work Group will continue to review safety data
VaST is preparing to transition review of vaccine safety data to the ACIP COVID -19
Vaccines Work Group
9VaST –future plans
VaST Members
VaST Members
Keipp Talbot (ACIP)
Robert Hopkins (NVAC)
Matt Daley
Grace Lee
Veronica McNallyKathy EdwardsLisa JacksonJennifer NelsonLaura Riley
Robert Schechte r
Patricia Whitley -Williams
CDC Co -Leads
Lauri Markowitz
Melinda WhartonEx Officio and Liaison Representatives
Tatiana Beresnev (NIH)Karen Farizo; Hui Lee Wong (FDA)
Valerie Marshall (OIDP)
Jeffrey Kelman (CMS)Matthew Clark (IHS)Timothy Styles (HRSA)Fran Cunningham (VA)
Margaret Ryan (DoD)
Administrative Support
Jared Woo
1010

Summary: COVID-19 Vaccine Safety Technical (VaST)  Work Group  VaST assessment H. Keipp Talbot, MD MPH (VaST Chair) Robert H. Hopkins, Jr., MD (NVAC Chair ) Advisory Committee on Immunization Practices February 24, 2023 COVID -19 Vaccine Safety Technical (VaST) Work Group Objectives Review, evaluate, and interpret post -a uthorization/approval COVID -19  vaccination safety data Serve as the central hub for technical subject matter expertise from  fe deral agencies conducting…


COVID 05 Twentyman 508

cdc.gov/coronavirus
Ischemic Stroke, COVID -19 and Influenza in
Adults Ages ≥65 Years:
Interpretation & Next Steps
Evelyn Twentyman, MD, MPH
ACIP MeetingFebruary 24, 2023
Statistical signal for
ischemic stroke identified in Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) monitoringIschemic stroke, COVID -19, and influenza in review
New and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps
Statistical signal for
ischemic stroke identified in VSD RCA monitoringIschemic stroke, COVID -19, and influenza in review
New and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps
Statistical signal identified for ischemic
s
troke after Pfizer -BioNTech COVID -19
mRNA bivalent booster dose vaccination in age group 65+ years in VSD RCA
–Rate ratio has attenuated over timeReview of statistical signal
:
Supplemental analysis comparing b
oosted to un -boosted concurrent
comparators did not show an elevated rate ratio:
Comparing rates in an early (“risk”) interval with rates in a later (“comparison”) intervalComparing rates in the early (“risk”) interval among boosted people vs booster eligible un-boosted people
Stratified analysis evaluating people
w
ith coadministration of high -dose or
adjuvanted flu vaccination show a rate ratio of 1.65 (1.02—2.72; p=0.04)In the stratified analysis, rate ratio w
as not elevated in people who
received Pfizer- BioNTech bivalent
mRNA booster without simultaneous
flu vaccine
Separate analysis did no t detect an
elevated rate ratio for ischemic stroke after flu vaccine aloneReview of statistical signal: coadministration
*Coadministration refers to administration of >1 vaccine in the same day.Pfizer bivalent mRNA Coadministration*High -do se/ adjuvanted flu vaccine
No other VSD RCA pre -s pecified surveillance outcomes have signaled:
–
––
–
–––
–in any age groups,
fore ither of the mRNA COVID -19 bivalent booster vaccines, or
when data for the two mRNA vaccine types are combined.
No evidence of a safety signal for ischemic stroke in other safety monitoring
s
ystems, though analyses in these systems generally did not have the ability to
investigate coadministration with flu vaccine
Vaccine Adverse Events Reporting System (VAERS)
FDA Rapid Cycle Analysis (RCA) data in Centers for Medicare & Medicaid Services (CMS)Veterans Administration (VA) RCA in the VA Electronic Health Record (VA EHR)
Pfizer global monitoring
Other global public health and regulatory systems
•Canada
•European Union
•IsraelReview of statistical signal: not identified in any other
vaccine safety monitoring system
Statistical signal for
ischemic stroke identified in VSD RCAIschemic stroke, COVID -19, and influenza in review
New and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps
Incidence of AIS hospitalizations was 10 times higher during
the 3 days post COVID diagnosis (IRR 10.3, [9.9 –10.8])
compared with control periods, among Medicare beneficiaries
ages ≥65 years1
COVID cohort estimated incidence of AIS is 2.10% (1. 97—2.23)
within 6 months after COVID diagnosis2, though stroke and
COVID symptoms present concomitantly in >80% of cases3
COVID -1 9 patients who develop stroke are more likely to be of older age, have more severe COVID- 19 disease , and more
likely to have hypertension, diabetes, and coronary artery disease than those who do not
3
COVID -19v accination is associated with reduced risk of AIS
after COVID -19 (aHR 0.40 [0.26-0.63]; aHR 0.41 [0.26- 0.66] for
ages ≥65)4Percentage Hospitalized
COVID Patients Aged 65+
with Stroke:
COVID -NET, March
2020—October 2022COVID -19 disease and acute ischemic stroke (AIS)
1) Yang Q et al. Neurology 2022; 98(8): e778- 789. 2) Taquet M et al. Lancet Psychiatry 2021; 8(5): 416- 427. 3) Nannoni S et al.  International Journal of Stroke 2021; 16(2):
137-149. 4) Kim Y et al. JAMA 2022; 328(9): 887- 889.1%2%3%
Alpha Delta Omicron
(early)Omicron
(late)2.2%
overall
Association between recent respiratory infection and increased stroke risk noted in
so
me observational studies 1,2
Two randomized studies assessing stroke as a specific outcome did not note a s
ignificant effect of influenza vaccination on stroke risk 3, 4
Stroke has been evaluated as an outcome in several observational studies, some of w
hich have reported decreased risk with vaccination 5-8
Benefit of influenza vaccination has been noted in some studies examining major c
ardiovascular outcomes (some including stroke within a composite outcome) 4,8
Limitations:
––––Potential reduction in stroke risk varies and is not seen in all studiesPopulations, study designs, outcome definitions, and analytic methods vary across studiesObservational data are more subject to biasOverall limited data concerning specific influenza vaccines and stroke -s
 pecific riskInfluenza, Influenza Vaccination, and Stroke
1. Smeeth L et al, N Engl J  Med 2004; 351: 2611 -8
2. Zurrú M C et al, Stroke 2009; 40: 1986 -90
3. Loeb M et al, Lancet Global Health 12 2022; 10: e1835 -e 1844
4. Phrommintikul A et al, Eur Heart J 2011; 32: 1730 –17355. Holodinsky JK  et al, Lancet Resp Health 2022; 7:  e914 -e922
6. Rodriguez -M artin S et al, Neurology 2022; 00: e2199 -e2160
7. Asghar Z et al, Vaccine 2015; 33: 5458 -5463
8. Chiang MH et al, Am Heart J 2017; 193: 1 -7
PCORnet©The National Patient -
Centered Clinical Research Network
Data includes el ectronic health records
associated with ambulatory, ED, and
inpatient settings
Covers a ll patients in participating
health systems, or ~ 10% of the US
population ages ≥65 years
Used to rapidly assess incidence of s
troke across diverse US population over
the late Omicron period within 2022, with recent COVID-19 or influenza and incidence overallHealthVerity
Data includes m edical claims from closed
payor systems related to ambulatory, ED, and inpatient settings
Data is l
inked to vaccination data from
the Federal Retail Pharmacy Program
Covers patients i nsured through
Medicare Advantage, or ~25% of the US population ages ≥65 years
Used to rapidly assess incidence of stroke a
cross insured US population, with
recent COVID-19 or influenza vaccination and incidence overallHealthcare data sources used to describe current
incidence of stroke
PCORnet©The National Patient -Centered
Clinical Research Network
Cohort definitions designed to capture
i
ncident stroke
––
–
–
–
–
–
––––
–
–
–
–ICD10 diagnosis (I63.X)Exclusion of
 patients with history of stroke
Cohort definitions designed to capture p
atients with recent COVID -19 and influenza
Positive laboratory tests (COVID -19 and influenza)
ICD10 diagnoses (B97.29, U07.1, J10.1, J10.2, J11.1, J 11.2,
J09.X, J10.8X, J11.8X)COVID -19 m
edicationsNo COVID -19 i
 n the 30 days prior
Description of incidence of stroke across:
Entire cohort, using average incidence over 32 days
Recent COVID or flu diagnosis: 3 days prior to 28 days p ostHealthVerity
Cohort definitions designed to capture i
ncident stroke
ICD10 diagnosis (I63.X)Inpatient place of serviceExclusion of
 patients with history of stroke
Cohort definitions designed to capture r
ecent bivalent mRNA and influenza
vaccination
All applicable CVX, CPT/HCPCS, and NDC codesNo evidence of prior s
 troke/TIA during observation
period or COVID -19 in the 30 days prior
Description of incidence of stroke across:
Entire cohort, using average incidence over 29 daysRecent vaccination: within 28 days following bivalent m
RNA vaccination, flu vaccination, or
coadministration of both vaccinesMethods used to describe current incidence of stroke
010002000300040005000600070008000900010000
*Average stroke incidence among adults aged 65+ in Sep -Dec 2022 in the full PCORnet cohort per million over 32 days.Stroke incidence among all adults ages ≥65 years, with COVID -19, and with
influenza during late Omicron: PCORnet , Sep- Dec 2022Stroke incidence per million
All adults ≥65 ,
over 32 days*All adults ages ≥65
(N=1,953,391)
Adults ages ≥65 with COVID-19 (N=77,981)
Adults ages ≥65 with influenza (N=11,396)
Adults ≥65 with
influenza ,
-3 to 28 daysAdults ≥65 with
COVID -19,
-3 to 28 daysGroups presented are of the
same agecategory and
adjusted time at risk. Crude
incidence within groups is not
otherwise adjusted.
010002000300040005000600070008000900010000
*Average stroke incidence among adults aged 65+ in Sep -Dec 2022 in the full PCORnet cohort per million over 32 days.Early stroke incidence among adults ages 65+ years with COVID -19, and with
influenza during late Omicron: PCORnet , Sep- Dec 2022Stroke incidence per million
All adults ≥ 65,
over 32 days*All adults ages ≥65
(N=1,953,391)
Adults ages ≥65 with COVID-19 (N=77,981)
Adults ages ≥65 with influenza (N=11,396)
Adults ≥65 with
influenza ,
-3 to 28 daysAdults ≥65 with
COVID -19,
-3 to 28 daysIncidence within -3
to 7 days of
COVID-19 disease
(93.5%)Incidence within -3
to 7 days of
influenza infection
(90.9%)
Groups presented are of the
same agecategory and
adjusted time at risk. Crude
incidence within groups is not
otherwise adjusted.
02004006008001000120014001600Stroke incidence among all adults ages ≥65 years and recently vaccinated
adults ages 65+ years during late Omicron: HealthVerity, Sep -Oct 2022
*Average stroke incidence among adults aged 65+ in Sep -Oct 2022 in the full HealthVerity cohort per million over 29 days.Stroke incidence per millionAll adults ages ≥65
(N=3,651,579)
Adults ages ≥65 with
recent bivalent mRNA
vaccination(N=593,766)
Adults ages ≥65 with
recent influenza
vaccination(N=875,170)
Adults ages ≥65 with
recent coadministration
of bivalent mRNA + influenza vaccines (N=164,836)
Adults ≥65 with
flu vaccine ,
0 to 28 daysAdults ≥ 65 with
bivalent mRNA ,
0 to 28 daysAdults ≥65 with
coadministration,
0 to 28 daysAll adults ≥65 ,
over 29 days*Groups presented are of the same
agecategory and adjusted time at
risk. Crude incidence within groups
is not otherwise adjusted.
Statistical signal for
ischemic stroke identified in VSD RCA monitoringIschemic stroke, COVID -19, and influenza in review
New and published data regarding relationships of ischemic stroke, COVID -19 disease, and
influenza Work group interpretation and next steps
Review of safety data is reassuring, and must continue. Priorities include:
–
–
–
–Continuing to closely follow the intermittently statistically significant signal in VSD,
w
ith continued review by VaST and colleagues
Continuing supplementary analyses to clarify the relationship between this signal an
d:
•any specific vaccine
•coadministration of vaccines
•confounding
Continuing the most intensive vaccine safety surveillance in US history
Review of healthcare data demonstrates high incidence of stroke at time of diagnosis w
ith COVID -19 or influenza. Priorities include:
Increasing awareness of the risk of stroke with COVID -1 9 disease and influenza
–Continuing to encourage uptake of the bivalent COVID -1 9 boostersWork group interpretation and next steps
The COVID -1 9 ACIP Work Group remains confident in current COVID -
19 vaccine recommendations.
–No changes to current recommendations regarding
coadministration of vaccines
CDC and partners anticipate the opportunity to review and consider
upc
oming analyses prior to the 2023 -2024 flu season.Work group interpretation and next steps
Tegan Boehmer
Matt Ritchey
Julia Raykin
Sharon Saydah
Stacey Adjei
Jennifer Wiltz
Jason Block
PCORnet Sites
Sara Baca
Lisa Groskopf
Jill Ferdinands
Janet Wright
Fátima Coronado
Sandra JacksonAcknowledgements
VaST Working Group
Lauri Markowitz
Robert Merritt
Xin (Cindy) Tong
Hilda Razzaghi
Catherin Bozio
Morgan Najdowski
Shikha Garg
Carrie Reed
Aaron Kite -Powell
Kathleen Hartnett
Fiona Havers
Chris Taylor
COVIDNetAdi Gundlappali
Aaron Harris
Emily Koumans
Pragna Patel
Jennifer Giovanni
Mark Swancutt
Karl Soetebier
Tom Shimabukuro
Eric Weintraub
Karen Broder
Immunization Safety
Office
Erika Edding
Aron HallSara Oliver
Katherine Fleming -
Dutra
Ruth Link -Gelles
Danielle Moulia
Megan Wallace
Monica Godfrey
Julianne Gee
Kelcie Landon
Ben Silk
Sarah Meyer
Elisha Hall
Melinda Wharton
Barbara Mahon
For more information, contact CDC
1-800-CDC- INFO (232- 4636)
TTY:  1 -888- 232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or
any use by other CDC CIOs or any external audiences.

Summary: cdc.gov/coronavirus Ischemic Stroke, COVID -19 and Influenza in  Adults Ages ≥65 Years: Interpretation & Next Steps Evelyn Twentyman, MD, MPH ACIP MeetingFebruary 24, 2023 Statistical signal for  ischemic stroke identified in Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) monitoringIschemic stroke, COVID -19, and influenza in review New and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps Statistical signal…


COVID 06 Taylor 508

National Center for Immunization & Respiratory Diseases
Trends in COVID -19-Associated Hospitalizations —COVID -19-Associated
Hospitalization Surveillance Network (COVID -NET), March 2020–February 2023
Christopher A. Taylor, PhD
Epidemiologist, COVID -NET
Coronaviruses and Other Respiratory Viruses Division
National Center for Immunizations and Respiratory DiseasesCenters for Disease Control and Prevention
Advisory Committee on Immunization Practices
February 24, 2023

Weekly Population-Based Rates of COVID -19-Associated Hospitalizations
among All Ages —COVID -NET, March 2020 –February 2023
020406080100120140
3/7/2020
4/7/2020
5/7/2020
6/7/2020
7/7/2020
8/7/20209/7/2020
10/7/202011/7/2020
12/7/2020
1/7/2021
2/7/2021
3/7/2021
4/7/2021
5/7/2021
6/7/2021
7/7/2021
8/7/20219/7/2021
10/7/202111/7/2021
12/7/2021
1/7/2022
2/7/2022
3/7/2022
4/7/2022
5/7/2022
6/7/2022
7/7/2022
8/7/20229/7/2022
10/7/202211/7/2022
12/7/2022
1/7/2023Rate per 100,000 population
Week Ending Date
≤17 years 18–49 years 50–64 years 65–74 years ≥75 years
Gray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 2
Weekly Population-Based Rates of COVID -19-Associated Hospitalizations
among Adults Ages ≥18 Years — COVID -NET, March 2020 –February 2023
020406080100120140Rate per 100,000 population
Week Ending DateMarch 2020 –February 2023 (entire pandemic period)
18–49 years 50–64 years 65–74 years ≥75 years020406080100120140Rate per 100,000 population
Week Ending DateAugust 2022– February 2023
Gray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 3
Weekly Population -Based Rates of COVID -19-Associated Hospitalizations among
Children and Adolescents Ages ≤17 Years —COVID- NET, March 2020 –February 2023
0102030405060708090Rate per 100,000 population
Week Ending DateAugust 2022– February 2023
0102030405060708090Rate per 100,000 population
Week Ending DateMarch 2020 –February 2023 (entire pandemic period)
<6 months 6 months–<2 years 2–4 years 5–11 years 12–17 years
Gray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 4
Weekly Proportions of COVID-19-Associated Hospitalizations by
Adult Age Group — COVID-NET, March 2020 –February 2023
0%10%20%30%40%50%60%70%80%90%100%
3/7/2020
4/11/2020
5/16/2020
6/20/2020
7/25/2020
8/29/202010/3/202011/7/2020
12/12/2020
1/16/20212/20/20213/27/2021
5/1/20216/5/2021
7/10/20218/14/20219/18/2021
10/23/2021
11/27/2021
1/1/20222/5/2022
3/12/20224/16/20225/21/20226/25/20227/30/2022
9/3/2022
10/8/2022
11/12/2022
12/17/2022
1/21/2023March 2020 –February 2023 (entire pandemic period)
18–49 years 50–64 years 65–74 years ≥75 years0%10%20%30%40%50%60%70%80%90%100%
8/6/2022
8/20/2022
9/3/2022
9/17/2022
10/1/2022
10/15/2022
10/29/2022
11/12/2022
11/26/2022
12/10/2022
12/24/2022
1/7/2023
1/21/2023
2/4/2023August 2022– February 2023
40% of hospitalizations are
in adults ages ≥75 years .
5
Weekly Proportions of COVID-19-Associated Hospitalizations by
Pediatric Age Group — COVID-NET, March 2020 –February 2023
0%10%20%30%40%50%60%70%80%90%100%
3/7/2020
4/11/2020
5/16/2020
6/20/2020
7/25/2020
8/29/2020
10/3/2020
11/7/2020
12/12/2020
1/16/2021
2/20/2021
3/27/2021
5/1/2021
6/5/2021
7/10/2021
8/14/2021
9/18/2021
10/23/2021
11/27/2021
1/1/20222/5/2022
3/12/2022
4/16/2022
5/21/2022
6/25/2022
7/30/2022
9/3/2022
10/8/2022
11/12/2022
12/17/2022
1/21/2023March 2020 –February 2023 (entire pandemic period)
<6 months 6 months –<2 years 2–4 years 5–11 years 12–17 years0%10%20%30%40%50%60%70%80%90%100%
8/6/2022
8/20/2022
9/3/2022
9/17/2022
10/1/2022
10/15/2022
10/29/2022
11/12/2022
11/26/2022
12/10/2022
12/24/2022
1/7/2023
1/21/2023
2/4/2023August 2022– February 2023
6
Proportions of COVID- 19-Associated Hospitalizations with COVID -19 as a Likely Reason for
Admission by Age and Variant Predominance Period —COVID -NET, June 2020– November 2022
0102030405060708090100
Total 0–4 years 5–11 years 12–17 years 18–49 years 50–64 years ≥65 yearsWeight % of hospitalizations
Period of variant predominance
Pre-Delta (6/1/20–6/19/21)
Delta (6/20–12/18/21)
Omicron BA.1 (12/19/21–3/19/22)
Omicron BA.2 (3/20–6/18/22)
Omicron BA.5 and later (6/19 –11/30/2022)•Many children ages
≤4 years and adults
ages ≥50 years are
still admitted for
COVID.
•Adolescents and younger adults ( ages
12–49 years ) are
less likely to be
admitted for COVID .
7
Underlying Medical Conditions among Non -Pregnant Adults
Ages ≥18 Years — COVID-NET, June–November 2022
68.6
54.6
35.032.5 30.7
24.6
17.514.9
9.75.3
01020304050607080Weighted % of hospitalizations
Data are limited to hospitalizations where COVID -19 is a likely primary reason for admission.96% of hospitalized adults have
≥1 underlying medical condition .
8
Underlying Medical Conditions among Children and Adolescents
Ages ≤17 Years — COVID-NET, June– November 2022
13.1
11.2
8.8 8.8
7.9
6.7 6.6 6.4
5.3
3.5 3.4
2.62.2
02468101214Weighted % of hospitalizations
Data are limited to hospitalizations where COVID -19 is a likely primary reason for admission.49% of hospitalized children and
adolescents have no underlying
medical conditions .
9
Underlying Medical Conditions among Children and
Adolescents by Age Group —COVID-NET, June– November 2022
051015202530
<2 years 2–4 years 5–11 years 12–17 yearsWeighted % of hospitalizations
Asthma Prematurity Feeding tube dependence
Obesity Chronic lung disease, not including asthma Immunocompromising condition
Gastrointenstinal/liver Disease Blood disorders Chronic lung disease of prematurity
Autoimmune/inflammatory disease Abnormality of airway Diabetes
Data are limited to hospitalizations where COVID -19 is a likely primary reason for admission.10
Vaccination Status by Age Group among Non -Pregnant Adults
Ages ≥18 Years —COVID-NET, October– November 2022
Data are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Unvaccinated: No recorded doses of COVID -19 vaccine. Vaccinated, but no bivalent booster:
Completed a primary series with or without ≥1 booster dose but did not receive an updated bivalent booster dose. Updated bivalent booster : Received updated bivalent booster dose. Partially
vaccinated : Received at least one dose of COVID -19 but was not considered fully vaccinated at the time of a positive SARS -CoV-2 test. Pers ons with unknown vaccination status are excluded. 58.250.4
34.1
23.115.0 12.540.3
42.4
58.0
66.9 79.676.55.42.73.42.78.0
0%10%20%30%40%50%60%70%80%90%100%
5–11 years 12–17 years 18–49 years 50–64 years 65–74 years ≥75 yearsPercent of hospitalizations
Unvaccinated Vaccinated, but no bivalent booster Updated bivalent booster Partially vaccinated
11
Monthly Age-Adjusted Rates of Lab- Confirmed Hospitalizations by Vaccination Status
among Adults Ages ≥18 Years —COVID- NET, January 2021–December 2022
0100200300400500600700Rate per 100,000 population
Month of Admission
Unvaccinated Primary series Primary series & ≥1 booster
Primary series & ≥2 boosters Vaccinated, no bivalent booster Updated bivalent booster
Data are based on all hospitalizations regardless of reason for admission. Unvaccinated : No recorded doses of COVID -19 vaccine. Primary series ± ≥1 booster: Completed a primary series with or without ≥1
booster dose but did not receive an updated bivalent booster dose. Vaccinated, but no bivalent booster : Completed a primary series with or without ≥1 booster dose but did not receive an updated bivalent
booster dose. Updated bivalent booster : Received updated bivalent booster dose. Persons with partial or unknown vaccination status are excluded. See https://covid.cdc.gov/covid-data-tracker/#covidnet -
hospitalizations-vaccination for complete definitions of vaccination categories. In December 2022, compared to adults
who received an updated bivalent booster dose, the monthly rates of hospitalization were-16x higher among unvaccinated and
-2.6x higher in vaccinated adults without an updated booster dose.
12
Acknowledgments
Coronaviruses and Other Respiratory
Viruses Division (CORVD) (proposed):
RESP-NET Team (COVID -NET/RSV -NET):
•Fiona Havers
•Huong Pham
•Michael Whitaker
•Kadam Patel
•Jenny M ilucky
•Onika Anglin
•Bhoomija C hatwani
Many others in CORVD….State, Local, and Territorial h
ealth Department partners
RESP- N ET partners
Thank you.

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

Summary: National Center for Immunization & Respiratory Diseases Trends in COVID -19-Associated Hospitalizations —COVID -19-Associated  Hospitalization Surveillance Network (COVID -NET), March 2020–February 2023 Christopher A. Taylor, PhD Epidemiologist, COVID -NET Coronaviruses and Other Respiratory Viruses Division National Center for Immunizations and Respiratory DiseasesCenters for Disease Control and Prevention Advisory Committee on Immunization Practices February 24, 2023  Weekly Population-Based…


COVID 07 Britton 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.COVID -19 vaccine effectiveness updates
24 February 2023
Amadea Britton, MD, SM
Medical Officer, Vaccine Effectiveness and Policy Team
Centers for Disease Control and Prevention
Preliminary vaccine effectiveness (VE) of monovalent vaccines against
symptomatic infection in children aged 6 months –4 years (Pfizer -BioNTech)
and 6 months –5 years (Moderna)
Update on VE of bivalent vaccines against symptomatic infection in children
and adolescents aged 5 -17 years and adults aged ≥18 years
Update on VE of bivalent vaccines against severe disease in adults with a
focus on adults aged ≥ 65 yearsOrganization of presentation
2
Preliminary Estimates of Effectiveness of mRNA Vaccines in
Preventing Symptomatic SARS -CoV -2 Infection Among Children Aged 3 –5
Years —Increasing Community Access to Testing Program, United States, July
2022 –February 2023
Fleming -Dutra KE, Ciesla AA, Roper, LE et al. Preliminary Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing Symptomatic SARS- CoV-2 Infection
Among Children Aged 3 –5 Years — Increasing Community Access to Testing Program, United States, July 2022 –February 2023. MMWR Morb Mortal Wkly Rep
2023;72:177– 182. DOI: http://dx.doi.org/10.15585/mmwr.mm7207a3
3
Ages 6 months –
4 years
(Primary Series:
Pfizer -BioNTech)Primary Primary3–8 weeks
Primary
***At least
8 weeksAges 6 months –
5 years
(Primary Series: Moderna )PrimaryPrimary
**4–8 weeksPediatric COVID-19 Vaccine Primary Series Schedule*:
Ages 6 months –5 years (Moderna) and 6 months–4 years (Pfizer -BioNTech)
*On June 18, 2022, ACIP issued interim recommendations for the use of the Moderna COVID -19 vaccine for children aged 6 months –5 years and for the Pfizer -BioNTech COVID- 19 vaccine for children aged 6
months –4 years.
** As of December 9, 2022, children who received 2 doses of monovalent Moderna vaccine are recommended to receive a single bi valent booster dose at least 2 months after their last primary series dose.
***As of December 9, 2022, children who received 2 doses of monovalent Pfizer -BioNTech vaccine primary series are recommended to receive a bivalent dose as their third dose.Earliest date for a child to
have a “complete series”=
August 1, 2022
Earliest date for a child
to have a “complete
series”=
September 19, 2022
4
Percent of people receiving COVID-19 vaccine by age and date administered
–United States, December 14, 2020 – February 15, 2023
https://covid.cdc.gov/covid -data- tracker/#vaccination -demographics -trends 5

Nationwide community -b ased drive -through SARS-CoV -2 testing via pharmacies
Self- r eported vaccine history at time of registration for COVID -19 testing
Design : T est -negative, case -control analysis*
Population: Immunocompetent children 3 –4 /5** years with ≥1 COVID -like symptom
and nucleic acid amplification testing (NAAT)
Period for analysis:
•Tested: July 4, 2022*** –F ebruary 5, 2023, BA.4/BA.5 predominant period, but
includes XBBIncreasing Community Access to Testing (ICATT) Program: VE of monovalent
COVID -19 vaccines against symptomatic infection in children aged 3-5 years
*Models adjusted for: age, gender, race, ethnicity, social vulnerability index and HHS region of the testing location, underlyin g conditions (presence versus absence), pharmacy
chain conducting the test, local incidence (cases per 100,000 by individual county and state in the 7 days before test date), and date of testing.
** ICATT testing is generally limited to children ages 3 and up.
***Analysis start date depended on vaccine/dose number being analyzed: Pfizer and Moderna 1stdoses started 7/4/2022; Pfizer 2nddose started 7/25/2022; Moderna 2nddose
started 8/1/2022; Pfizer 3rddose started 9/19/2022.6
ICATT: Preliminary estimates of VE for primary series monovalent Moderna vaccine
(children aged 3– 5 years) against symptomatic infection , July 4, 2022 –February 5, 2023
7Fleming -Dutra, Ciesla, Roper, et al. MMWR February 16, 2023.
*Test registrants who report receiving COVID -19 vaccines are asked to report the total number of doses and manufacturer(s) of va ccines
received and for the most recent dose, month and year of receipt; therefore, the number of months between a vaccine dose and tes ting is a
whole number calculated as the difference between the month and year of testing and the month and year of the vaccine dose. F or doses
received in the same month or the month before SARS -CoV- 2 testing, an additional question was asked to specify whether the dose was
received ≥2 weeks before testing, and only doses received ≥2 weeks before testing were included. 17% and 21% of children who received 1
and 2 doses of Moderna, respectively, reported a prior infection >90 days before the current test.Vaccination status (months since last dose)Total
testsSARS-CoV -2
positive, N (%)Adjusted
VE (95% CI)
Moderna, 1 dose (partial series; ages 3-5 years)
July 4, 2022 –February 5, 2023
Unvaccinated 34,982 9,523 (27) Ref
1monovalent dose (2 weeks– 1 month)* 509 107 (21) 40 (26 to 52)
Moderna, 2 doses (complete series; ages 3-5 years)
August 1, 2022 –February 5, 2023
Unvaccinated 25,049 5,690 (23) Ref
2 monovalent doses (2 weeks– 2 months)* 816 81 (10) 60 (49 to 68)
2 monovalent doses (3 –4 months)* 495 58 (12) 36 (15 to 52)
-20 0 20 40 60 80 100
V accine E ffectiveness (%)
ICATT: Preliminary estimates of VE for primary series monovalent Pfizer -BioNTech vaccine
(children aged 3– 4 years) against symptomatic infection , July 4, 2022 –February 5, 2023
8Fleming -Dutra, Ciesla, Roper, et al. MMWR February 16, 2023.
*Test registrants who report receiving COVID -19 vaccines are asked to report the total number of doses and manufacturer(s) of va ccines
received and for the most recent dose, month and year of receipt; therefore, the number of months between a vaccine dose and tes ting is a
whole number calculated as the difference between the month and year of testing and the month and year of the vaccine dose. F or doses
received in the same month or the month before SARS -CoV- 2 testing, an additional question was asked to specify whether the dose was
received ≥2 weeks before testing, and only doses received ≥2 weeks before testing were included. 18%, 19% and 21% of children who
received 1, 2, and 3 doses of Pfizer, respectively, reported a prior infection >90 days before the current test.
**There was insufficient power to stratify Pfizer -BioNTech 3 -dose VE estimates by time since vaccination.Vaccination status (months since last dose)Total
testsSARS- CoV-2
positive, N (%)Adjusted
VE (95% CI)
Pfizer, 1 dose ( partial series; ages 3 –4 years)
July 4, 2022 –February 5, 2023
Unvaccinated 22,323 6,212 (28) Ref
1 monovalent dose (2 weeks –1 month)* 443 114 (26) 19 (-1 to 35)
Pfizer, 2 doses ( partial series; ages 3 –4 years)
July 25, 2022 –February 5, 2023
Unvaccinated 17,434 4,298 (25) Ref
2 monovalent doses (2 weeks– 3 months)* 933 137 (15) 40 (28 to 50)
Pfizer, 3 doses ( complete series; ages 3 –4 years)**
September 19, 2022 –February 5, 2023
Unvaccinated 7,548 1,273 (17) Ref
3 monovalent doses (2 weeks– 4 months)* 395 53 (13) 31 (7 to 49)
-20 0 20 40 60 80 100
V accine E ffectiveness (%)
Vaccine coverage is low in children ≤5 years. VE estimates may
be
 less stable when vaccine coverage is low.
Prevalence of prior infection in children is hig h* ; consequently,
vaccine effectiveness in this analysis reflects the current situation among young children in the United States.
Low vaccination coverage in this age group may impact future a
bility to estimate VE, including against more severe outcomes.Limitations
*https://covid.cdc.gov/covid-data-tracker/#pediatric-seroprevalence.9
Complete mo novalent primary vaccination series helped provide protection for
children aged 3 –5 years against symptomatic SARS -CoV-2 infection for at least the
first 4 months after vaccination.
Waning of monovalent M oderna primary series might occur by 3 –4 months after the
second dose based on point estimates (although confidence intervals overlapped).
This is similar to patterns observed in older children and adults in the first months
after vaccination.
–Waning of monovalent Pfizer -B ioNTech VE against symptomatic infection could not be assessed but is also
likely based on analyses in older children and adults.
Children should stay up to date with COVID -1 9 vaccines, including completing the
primary series; those who are eligible should receive a bivalent vaccine dose.
CDC will continue to monitor VE in this age group, including against severe disease an
d for bivalent doses.Conclusions
10
Updated estimates of VE against
symptomatic infection among children and
adolescents aged 5– 17 and adults aged ≥18
years
11
Absolute VE: c omparing the frequency of health outcomes in vaccinated and
unvaccinated people
–
–E.g., comparing outcomes in people vaccinated with an updated bivalent booster versus no
vaccine at all
Relative VE: c omparing the frequency of health outcomes in people who received
one type of vaccine to people who received a different vaccine or by comparing
people who received more vaccine doses to those who received fewer doses
E.g., comparing outcomes in people vaccinated with an updated bivalent booster versus
monovalent vaccine only
In the analyses presented today, relative vaccine effectiveness can be interpreted as th
e additional protection provided by an updated bivalent booster among people
who already received monovalent COVID -19 vaccinesInterpreting absolute and relative vaccine effectiveness
12
Nationwide community- bas ed drive -through SARS-CoV -2 testing via pharmacies
Self-repo rted vaccine history at time of registration for COVID -19 testing
Design:  Test -negative, case -control analysis*
Population :  Children and adolescents aged 5–17 years and adults aged ≥18 years with ≥1 COVID -like
symptom and nucleic acid amplification testing (NAAT)
Exclusion criteria: E xcluded individuals <4 months from last monovalent dose and individuals with
immunocompromising conditions
Periods for analysis:
•Tested: December 1, 2022 –F ebruary 13, 2023**
•Includes periods of both BA.5-rel ated sublineage and XBB/XBB.1.5 sublineage predominanceICATT: Relative VE of bivalent booster against symptomatic infection in
children and adolescents aged 5 –17 years and adults aged ≥18 years
*Models adjusted for: age, gender, race, ethnicity, social vulnerability index and HHS region of the testing location, underlyin g conditions (presence versus absence), local incidence (cases per 100,000 by individual county and
state in the 7 days before test date), and date of testing
**Analysis is an update of data published in Link -Gelles R, Ciesla AA, Roper LE, et al. Early estimates of bivalent mRNA booster dose vaccine effectiveness in preventing symptomatic SARS -CoV- 2 infection attributable to SARS -
CoV- 2 Omicron BA.5 -related and XBB/XBB.1.5 -related sublineages among immunocompetent adults —Increasing Community Access to Testing Program, United States, December 2022 –January 2023. MMWR Morb Mortal Wkly
Rep 2023;72.  https://www.cdc.gov/mmwr/volumes/72/wr/mm7205e2.htm13
ICATT: Relative VE of bivalent booster against symptomatic infection in children and
adolescents aged 5– 17 years, December 1, 2022 –February 13, 2023*
*Unpublished CDC data. 14Age group, years/mRNA Dosage PatternTotal
testsSARS-CoV -2
positive tests, Adjusted VE
N (row %) (95% CI)
5-11 years (authorized for bivalent booster
on October 12, 2022)
Received 2 -3monovalent doses only (Ref) 4,855 1,433 (30) Ref
2 weeks -1 month since bivalent booster 600 73 (12) 65 (55 to 73)
2-3 months since bivalent booster 881 139 (16) 54 (43 to 62)
4-5 months since bivalent booster 58 10 (17) ----
12-17 years (authorized for bivalent booster
on September 1, 2022)
Received 2 -3 monovalent doses only (Ref) 8,243 3,194 (39) Ref
2 weeks -1 month since bivalent booster 443 73 (16) 68 (58 to 75)
2-3 months since bivalent booster 1,122 230 (20) 56 (49 to 62)
4-5 months since bivalent booster 283 68 (24) 53 (37 to 64)
0 20 40 60 80 100
Vaccine Effectiveness %
ICATT: Relative VE of bivalent booster against symptomatic infection in adults aged
≥18 years, December 1, 2022 –February 13, 2023*
*Unpublished CDC data. 15Age group, years/mRNA Dosage PatternTotal
testsSARS- CoV-2
positive tests, Adjusted VE
N (row %) (95% CI)
18-49 years
Received 2 -3 monovalent doses only (Ref) 182,741 82,043 (45) Ref
2 weeks -1 month since bivalent booster 10,758 3,127 (29) 51 (49 to 53)
2-3 months since bivalent booster 32,577 10,206 (31) 45 (43 to 46)
4-5 months since bivalent booster 9,197 2,882 (31) 41 (38 to 44)
50-64 years
Received 2 -4 monovalen t doses only (Ref) 60,822 31,878 (52) Ref
2 weeks -1 month since bivalent booster 6,223 2,331 (37) 46 (43 to 49)
2-3 months since bivalent booster 18,399 7,898 (43) 32 (29 to 34)
4-5 months since bivalent booster 4,837 2,030 (42) 28 (23 to 32)
≥65 years
Received 2 -4 monovalent doses only (Ref) 28,307 14,246 (50) Ref
2 weeks -1 month since bivalent booster 4,579 1,788 (39) 38 (34 to 42)
2-3 months since bivalent booster 19,071 8,080 (42) 27 (25 to 30)
4-5 months since bivalent booster 5,796 2,431 (42) 21 (16 to 26)
0 20 40 60 80 100
Vaccine Effectiveness %
Updated estimates of VE against
emergency department/urgent care encounters
and hospitalizations among adults aged ≥18 years, VISION Network
VISION Multi -State Network of Electronic Health Records
Variant periods designated for
analysis based on time when novel sublineage became predominant at
study site
VE a djusted for age, sex, race,
ethnicity, geographic region, calendar time, and local rates of SARS -CoV -2 circulation
Vaccination documented by electronic health records and state and city registriesCases : COVID -like illness (CLI) with
positive PCR for SARS- CoV-2 within 14
days before or 72 hours after the
admission or encounter
Controls : CLI with negative PCR for SARS-
CoV-2
 17
mRNA Dosage PatternTotal
testsSARS- CoV-2-
test-positive,
N (%)Median interval
since last dose,
days (IQR)Adjusted VE
(95% CI)
Emergency department/urgent care encounters
Aged 18 -64 years
Unvaccinated (Ref) 56,560 6,632 (12) — Ref
Monovalent doses only, last dose ≥2 months earlier 79,203 8,848 (11) 370 (300- 508) 2 (-2 to 5)
Aged ≥65 years
Unvaccinated (Ref) 11,277 2,026 (18) — Ref
Monovalent doses only, last doses ≥2 months earlier 37,505 5,588 (15) 335 (196- 424) 12 (6 to 17)
Hospitalizations
Aged 18 -64 years
Unvaccinated (Ref) 6,213 475 (8) — Ref
Monovalent doses only, last doses ≥2 months earlier 7,250 501 (7) 360 (281- 502) 19 (7 to 30)
Aged ≥65 years
Unvaccinated (Ref) 4,795 819 (17) — Ref
Monovalent doses only, last doses ≥2 months earlier 14,462 1924 (13) 337 (205- 439) 28 (22 to 34)VISION: Absolute VE of ≥2monovalent doses against ED/UC encounters and
hospitalizations among adults aged ≥18 years –September 2022 –January
2023*
*Unpublished CDC data.-20 0 20 40 60 80 100
Vaccine Effectiveness (%)
18
VISION: Relative VE of bivalent booster against ED/UC encounters and
hospitalizations among adults aged ≥18 years –September 2022 –January
2023*
*Unpublished CDC data. 19mRNA Dosage Pattern Total testsSARS -CoV-2-
test-positive,
N (%)Median
interval
since last
dose,
days (IQR)Adjusted VE
(95% CI)
Emergency department/urgent care encounters
Monovalent doses only, last dose ≥2 months earlier 112,857 13,429 (12) 359 (279- 496) Ref
Bivalent booster, 7 -59 days earlier 12,546 948 (8) 33 (20 -46) 50 (46 to 53)
Bivalent booster, 60 -119 days earlier 5,952 617 (10) 76 (67 -87) 36 (30 to 41)
Hospitalizations
Monovalent doses only, last dose ≥2 months earlier 28,227 3,187 (11) 348 (243- 484) Ref
Bivalent booster, 7 -59 days earlier 2,809 202 (7) 32 (19 -45) 52 (44 to 58)
Bivalent booster, 60 -119 days earlier 1,281 155 (12) 74 (67 -85) 31 (18 to 42)
0 20 40 60 80 100
Vaccine Effectiveness (%)
Preliminary estimates of VE against
hospitalizations among adults aged ≥65 years,
IVY Network
IVY Network —24 hospitals, 19 U.S. States
Design : P rospective test-negative, case -control
Period :  September 8, 2022 –January 30, 2023
Population: Immunocompetent adults
h
ospitalized with COVID -like illness (CLI)
Participants have CLI and SARS-C oV-2 test:
–
–Cases: S ARS -CoV-2-positive by RT -PCR or
antigen
Controls: S ARS -CoV-2-and influenza- negative
by RT -PCR
VE adjustments: Ag e, sex, race/ethnicity,
admission date (biweekly), and HHS region
21
Vaccinated
cases,
N/total cases
(%)Vaccinated
controls,
N/total
controls
(%)Median
interval
since last
dose,
days (IQR)Adjusted
VE,
% (95% CI)
Absolute monovalent VE against hospitalization
Unvaccinated (Ref) -- Ref
≥2 Monovalent doses, last dose ≥2 months earlier 550/707 (78) 645/810 (80) 352 (224- 432) 17 (- 7 to 36)
Relative bivalent VE against hospitalization
≥2 Monovalent doses, last dose ≥2 months earlier (Ref) 352 (224- 432) Ref
Bivalent booster dose, ≥7 days earlier 108/658 (16) 255/900 (28) 56 (30 –84) 52 (37– 64)
Absolute bivalent VE against hospitalization
Unvaccinated (Ref) -- Ref
Bivalent booster dose, ≥ 7 days earlier 108/265 (41) 255/420 (61) 56 (30 –84) 55 (36– 69)IVY: Absolute VE of ≥2 monovalent doses and relative VE of bivalent booster against
COVID -19 hospitalizations among adults aged ≥65 years —IVY Network, September 8,
2022– January 30, 2023*
*Unpublished CDC data.-20 0 20 40 60 80 100
Vaccine Effectiveness (%)
22
Vaccinated
cases,
N/total cases
(%)Vaccinated
controls,
N/total
controls
(%)Median
interval
since last
dose,
days (IQR)Adjusted
VE,
% (95% CI)
Absolute monovalent VE against hospitalization
Unvaccinated (Ref) -- Ref
≥2 Monovalent doses, last dose ≥2 months earlier 550/707 (78) 645/810 (80) 352 (224- 432) 17 (- 7 to 36)
Relative bivalent VE against hospitalization
≥2 Monovalent doses, last dose ≥2 months earlier (Ref) 352 (224- 432) Ref
Bivalent booster dose, ≥7 days earlier 108/658 (16) 255/900 (28) 56 (30 –84) 52 (37– 64)
Absolute bivalent VE against hospitalization
Unvaccinated (Ref) -- Ref
Bivalent booster dose, ≥7 days earlier 108/265 (41) 255/420 (61) 56 (30 –84) 55 (36– 69)IVY: Absolute VE of ≥2 monovalent doses and relative VE of bivalent booster against
COVID -19 hospitalizations among adults aged ≥65 years —IVY Network, September 8,
2022– January 30, 2023*
*Unpublished CDC data.-20 0 20 40 60 80 100
Vaccine Effectiveness (%)
23
IVY: Severity of COVID-19 hospitalizations in bivalent booster VE analysis among
adults aged ≥65 years —IVY Network, September 8, 2022–January 30, 2023*
CharacteristicCase -patients, N (%)
N = 719**
Hypoxemia 427 (59)
High flow nasal cannula (HFNC) 78 (11)
Non -invasive positive pressure ventilation (NIPV) 51 (7)
Invasive mechanical ventilation (IMV) 47 (7)
HFNC, NIPPV, or IMV 138 (19)
ICU admission 116 (16)
In-hospital death on or before Day 28 38 (5)
*Unpublished CDC data.
**Data missing for 12% (96/815) of cases due to reporting lag.•Of all hospitalized cases, 59% had documented hypoxemia
•Approximately 16% of hospitalized cases required an ICU admission
•Some hospitalizations included in the analysis may not represent severe COVID -19 disease
24
Conclusions
For estimates of absolute v accine effectiveness, if unvaccinated or vaccinated
individuals are significantly different than the rest of the population, estimates may
be biased.
For estimates of relative v accine effectiveness, residual protection from prior doses is
an important consideration.
–
–Particularly important for severe disease, for which residual protection from prior doses may be higherCan be challenging to interpret waning of relative VE
Limited information on prior infection, although we know rates of prior infection in
t
he U.S. population are high.
VE against COVID -1 9 associated hospitalization may underestimate protection against
severe COVID -19 disease.Limitations
26
Updates to VE of bivalent C OVID -19 booster against symptomatic infection
among children and adolescents aged 5-17 years and adults aged ≥18 years
–
–Bivalent booster provided added protection, though early evidence of
waning of relative effectiveness
Updates to VE of bivalent C OVID -19 booster against ED/UC encounters and
hospitalizations among adults ≥18 years
Bivalent boosters are helping provide additional protection against e
mergency department/urgent care encounters and hospitalization
–For most people who received monovalent doses and are eligible for a bivalent booster, more than a year has elapsed since their last monovalent dose. Because of waning, they may have limited remaining protection.Conclusions
27
CDC COVID- 19 Vaccine Effectiveness and
Policy Team
Allison Ciesla
Monica Godfrey
Katherine Fleming -Dutr a
Ruth Link- G elles
Morgan Najdowski
Sara Oliver
Amanda Payne
Lauren Roper
Laura Steinhardt
Evelyn Twentyman
Megan Wallace
Ryan WiegandPIs and study staff for VE platforms
Sarah Ball
Jennifer DeCuir
Monica Dickerson
Margaret Dunne
Eric Griggs
Matthew Levy
Patrick Mitchell
Palak PatelAcknowledgements
28Sarah Reese
Heather Scobie
Zach Smith
Diya Surie
Zack Weber
Mark Tenforde
For more information, contact CDC
1-800-CDC- INFO (232- 4636)
TTY:  1 -888- 232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or
any use by other CDC CIOs or any external audiences.

Summary: Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…


COVID 08 Oliver 508

cdc.gov/coronavirus
Considerations for Bivalent Primary Series
Sara Oliver, MD, MSPH
ACIP MeetingFebruary 24, 2023
Does ACIP support h armonizing the vaccine strain composition for mRNA COVID- 19
vaccines across both primary series and booster doses:
Changing the primary series from monovalent (Original) to bivalent (Original plus Omicron
BA.4/5) for all ages?Question for consideration
2Mono-
valent Mono-
valent BivalentPeople ages 6 months and older*
Bivalent Bivalent BivalentPeople ages 6 months and older*Current recommendations
(Simplified representation)Future proposed recommendations
*Ages and vaccines as authorized by FDA and recommended by ACIP/CDC
For children ages 6 months -4 years of age who start a Pfizer -BioNTech
primary series, 3- dose primary series still needed*Ages and vaccines as authorized by FDA and recommended by ACIP/CDC
For children ages 6 months -4 years of age who start a Pfizer -BioNTech
primary series, the third dose in a 3 -dose primary series is a bivalent doseBooster dose
(in most ages) Primary seriesBooster dose
(in most ages) Primary series
Policy considerations for bivalent primary series
3Policy on bivalent primary series will be coordinated with F DAfor
regulatory action, and CDC/ACIP for recommendations for use
Review data
Discuss
considerations FDA
Regulatory
allowanceCDC/ACIP
Recommendations
for use
4Public
Health
ProblemConsiderations for Bivalent Primary Series
Coverage / Age (years) <2 2–4 5–11 12–17 18–24 24–49 50–64 >65
At least 1- dose 7.6 10.3 39.7 71.9 81.9 85.2 95.0 95.0
Completed primary series 3.7 5.5 32.6 61.6 66.5 72.0 83.7 94.2
1st monovalent booster* - - 3.3 16.6 27.2 45.3 64.6
2nd monovalent booster * - - - - - - 10.6 25.3
Bivalent booster** 0.2 0.3 4.0 7.0 6.7 11.2 20.3 40.8
Unvaccinated 92.4 89.7 60.3 28.1 18.1 14.8 —†—†U.S. COVID-19 Vaccination Coverage (%) of Total Population by
Age Group — February 8, 2023
*Monovalent booster dose coverage as of August 26, 2022
** Bivalent booster coverage is independent of 1stand 2nddose monovalent coverage
†Note: Coverage is capped at 95%
Source: https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends Updated February 10, 2023 5
Gray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. Weekly Population -Based Rates of COVID -19-Associated Hospitalizations among
Children and Adolescents Ages ≤17 Years —COVID- NET, March 2020 –February 2023
01020304050607080Rate per 100,000 population
Week Ending DateAugust 2022– February 2023
01020304050607080Rate per 100,000 population
Week Ending DateMarch 2020 –February 2023 (entire pandemic period)
<6 months 6 months–<2 years 2–4 years 5–11 years 12–17 years
Gray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks.
Underlying Medical Conditions among Children and Adolescents Ages ≤17 Years
—COVID -NET, June –November 2022
13.1
11.2
8.8 8.8
7.9
6.7 6.6 6.4
5.3
3.5 3.4
2.62.2
02468101214Weighted % of hospitalizations
Data are limited to hospitalizations where COVID -19 is a likely primary reason for admission.49% of hospitalized children and
adolescents have no underlying
medical conditions .
Age-adjusted rates of COVID -19-associated hospitalization by vaccination status and
receipt of booster dose in children and adolescents
COVID -NET, December 2021 -December 2022
CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalizations -vaccination Accessed February 10, 2023 8
Hospitalization rates by vaccination status
Adolescents ages 12 -17 years
Hospitalization rates by vaccination status
Children ages 5 -11 years
050100150200250300
0-5
months6-11
months1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17COVID -19 deaths
Age in yearsCOVID -19 deaths in children and adolescents by age based on death certificate
data, National Center for Health Statistics
January 1, 2020– February 11, 2023
Source: https://data.cdc.gov/NCHS/Provisional -COVID -19-Deaths-Counts- by-Age-in-Years/3apk -4u4f/data. Accessed February 16 , 2023  Children 6 months –17 years :
1489 COVID -19 deaths
1.4% of all deaths in this age group
Death rates by vaccination status and receipt of bivalent booster doses among
people ages 5 years and older April 3 –December 3, 2022 (23 U.S. Jurisdictions)
*Includes either a booster or additional dose.    Updated booster = Bivalent booster
CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#rates -by-vaccine- status Accessed February 10, 2023In November 2022, people ages
5 years and older with
bivalent booster had
12.7 times lower risk of dying
from COVID -19, compared
to unvaccinated people and
2.4 times lower risk of dying from
COVID-19 than people
vaccinated without
a bivalent booster
10

Children and adolescents can develop severe COVID- 19. Nearly 1500 children and
adolescents have died from COVID- 19 since the beginning of the pandemic
Half of the hospitalized children and adolescents had no underlying medical
conditions
During all periods, COVID- 19 hospitalizations and mortality were consistently higher
among unvaccinated persons than among persons who had completed a primary
series and/or an updated booster
Many children remain unvaccinated for COVID- 19Considerations for Bivalent Primary Series
Public Health Problem
Benefits
and
HarmsConsiderations for Bivalent Primary Series
12
Ongoing, Phase 3, open- l abel study (unpublished, data obtained from sponsor)
Children ages 6 months –5 y ears in United States
–
–Original primary series (historical control):  4,792 participants received 25 ug of
m
RNA- 1273
BA.1 bivalent primary series: 179 participants received 25 ug of mRNA -1 273.214
(12.5 ug original strain and 12.5 ug Omicron BA.1 strain)
Median follow- up f or the original vaccine was 102 days post Dose 1 and for the BA.1
bivalent vaccine was 85 days post Dose 1
Baseline SAR -Co V-2 positive was 8% for the original vaccine and 63% for the BA.1
bivalent vaccineModerna BA.1 bivalent primary series among children
ages 6 months –5 years
13
Immunogenicity of Moderna BA.1 bivalent primary series
among children ages 6 months –5 years
14Bivalent Vaccine Original Vaccine
Outcome Time point NGMTa(95% CI)N GMTa(95% CI)GMRb(95% CI) –
Bivalent vs. Original
BA.1
Neutralizing AntibodyPre Dose 1
5849.2 (30.4, 79.6)
4025.9 (5.5, 6.2)
Day 57 1889.7 (1430.0, 2497.2) 74.3 (67.7, 81.7) 25.42 (20.14, 32.07)
c
Original Strain Neutralizing AntibodyPre Dose 1
6635.6 (24.0, 52.7)
5949.6 (8.9, 10.4)
Day 57 1432.9 (1054.5, 1947.0) 1732.5 (1611.5, 1862.5) 0.83 (0.67, 1.02)
d
GMT = geometric mean titer; GMR = geometric mean ratio; CI=confidence interval
a  GMTs were estimated using an analysis of covariance (ANCOVA) model with neutralizing antibody values at Day 57 as the depend
variable and a group variable (mRNA -1273.214 vs mRNA -1273) as the fixed variable, adjusted by age group and by baseline SARS -CoV- 2
infection status. The GMT value at Day 57 was estimated by the geometric least square mean (GLSM) from the model.
b  GMRs were estimated by the ratio of the GLSMs with a 2- sided 95% CI from the model
c Met the pre -specified superiority success criterion (lower bound of the 95% CI > 1.0)
d Met the pre -specified non- inferiority success criterion (lower bound of the 95% CI > 0.667)
142 patients received two doses of the bivalent vaccine
Percentage of patients reporting solicited local or systemic events was similar to or
less than percentages seen after original vaccine, however this may be a result of the
larger percent of seropositive participants in the bivalent vaccine group
Pain, axillary (or groin) swelling or tenderness, and erythema were the most common local events
Irritability/crying, sleepiness, and fatigue were the most common systemic events
There were no Grade 4 solicited adverse events reported
There was one serious adverse events (SAE) of asthma exacerbation reported after the first dose that was assessed as unrelated to vaccination by the investigatorSafety of Moderna BA.1 bivalent primary series among children ages 6 months –5 years
Safety of Moderna BA.1 bivalent primary series among
children ages 6 months –5 years
From Jan 26, 2022 VRBPAC meeting : https://www.fda.gov/media/164810/download
Safety of Moderna BA.1 bivalent primary series among
children ages 6 months –5 years
From Jan 26, 2022 VRBPAC meeting : https://www.fda.gov/media/164810/download
Systemic reactions   6 –36months
Systemic reactions   37 months –5 years
Concern that initial exposure to one virus strain may primes B -c ell memory and limit the
development of memory B cells and neutralizing antibodies against new strains
Prior infection and/or vaccine history likely has impact on subsequent immune response1-3
Affinity maturation oc curs: the ability of memory B cells to mature over time, especially
when exposed to newer strains4-5
–Variant -s pecific vaccines can also initiate new variant -specific immune responses6-7
Clinical impact of different immune responses by prior exposure, or how it may differ by
i
nfection and vaccine, requires additional research
Vaccines continue to be able to provide a b road boost in antibody responses
Imprinting concerns related to in cremental benefit of updated variant- specific vaccinesConsiderations for Bivalent Primary Series:
Imprinting
1.Immune boosting by B.1.1.529 (Omicron) depends on previous SARS -CoV-2 exposure | Science
2.Imprinted SARS -CoV-2 humoral immunity induces convergent Omicron RBD evolution (nature.com)
3.Protective Effect of Previous SARS -CoV-2 Infection against Omicron BA.4 and BA.5 Subvariants | NEJM
4.Affinity maturation of SARS -CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations – ScienceDirect 185.The germinal centre B cell response to SARS-CoV -2 | Nature Reviews Immunology
6.SARS -CoV-2 Omicron boosting induces de novo B cell response in humans | bioRxiv
7.Molecular fate -mapping of serum antibody responses to repeat immunization (nature.com)
Several studies compared antibody titers with recent Omicron sub- l ineages for both the bivalent
and monovalent vaccines; most studies ranging from ~21 -42 days after bivalent vaccine
Ratio o f antibody titers from bivalent vaccine to monovalent vaccine shownComparing monovalent and bivalent vaccines
Antibody data
1. https://www.biorxiv.org/content/10.1101/2022.10.22.513349v1.full.pdf
2. https://www.nejm.org/doi/full/10.1056/NEJMc2213948
3. https://www.nejm.org/doi/full/10.1056/NEJMc2214314
4. https://www.biorxiv.org/content/10.1101/2022.10.31.514636v1
5. https://www.nature.com/articles/s41591 -022- 02162-x19Wang, et al1Collier, et al2 Davis -Gardner4 Kurhade, et al5 Miller, et al3012345678910
BA.4/5 BA.4/5 XBB.1 BA.4/5 XBB.1Bivalent to Monovalent Ratio of Antibody Titers
Pseudovirus neutralization assays Live virus neutralization assaysOverall, most studies show improvement
i
n neutralizing antibodies for Omicron
sub- lineages with a bivalent vaccine
(ratio >1 )
Clinical impact is unknown for specific r
atios or antibody levels
Neutralizing antibodies at a single time do no
t convey the entire immune response
Unable to directly compare clinical outcomes for monovalent and bivalent vaccines in
the
 U.S. due to timing of authorizations Comparing monovalent and bivalent vaccines
Clinical data
https://www.fda.gov/media/164810/download
A Randomized Trial Comparing Omicron -Containing Boosters with the Original Covid -19 Vaccine mRNA -1273 | medRxiv 20
Study in the UK found ~1 0%
increase in relative VE for COVID- 19
infections
Unable to estimate differential i
mpact for prevention of severe
COVID -19
Considerations for Bivalent Primary Series
Benefits and Harms
21Bivalent COVID-1 9 vaccines are able to induce an immune response when given
either as a primary series or a booster dose
Limited data to directly compare COVID -19  outcomes after receipt of a
monovalent or bivalent vaccine
COVID -1 9 vaccines have a high degree of safety. Initial safety data from bivalent
primary series trial are encouraging but study was not powered to assess rare adverse events
22Feasibility
and
ImplementationConsiderations for Bivalent Primary Series
Number of mRNA COVID-19 vaccine products currently
Moderna: 5 products Pfizer- BioNTech: 6 products
11 TOTAL Products!

Possible number of mRNA COVID-19 vaccine products with a
bivalent primary series
Moderna: 2 products Pfizer- BioNTech: 3 products
Could be reduced to
5 total products
Would eliminates look -alike vials for
Moderna and Pfizer-BioNTech
Transition to bivalent primary series could:
Improve s torage space
–
–
–
–
–Providers have limited storage space
In addition to monovalent and bivalent products, Vaccines for Children (VFC) stock required
t
o be duplicate and separate
Reduce errors
Would eliminate ‘look -alike’ vials
Currently, one of the most common administration errors reported is providers giving a bi
valent vaccine as a primary series
Allow for c ontinued access to primary series
Majority of current monovalent vaccine stock expires within the next few monthsConsiderations for Bivalent Primary Series
Feasibility and Implementation
25
Work is ongoing to evaluate cost effectiveness in preparation for a transition to
commercialization of COVID -19 vaccine
Bivalent COVID- 19 vaccines already purchased and delivered; transition of current
primary series recommendations from monovalent to bivalent vaccines unlikely to have significant impact on resource useConsiderations for Bivalent Primary Series
Resource Use
Summary
Considerations for Bivalent Primary Series
Summary
28Receiving a C OVID- 19 vaccine primary series continues to be important for
prevention of COVID- 19 severe disease, hospitalization, and death
Many children and adolescents remain unvaccinated for COVID- 1 9
COVID -19 vaccines recommendations that are simple to implement may remove
some barriers to uptake
Harmonizing the primary series and booster doses could simplify the presentations,
r
educe administration errors, and allow continued access to primary series for
unvaccinated populations
The Work Group was su pportive of a transition of the mRNA COVID- 19 vaccine
primary series from monovalent (original) to bivalent (original plus Omicron BA.4/5)
Monica Godfrey
Megan Wallace
Danielle Moulia
Evelyn Twentyman
Hannah Rosenblum
Lauren Roper
Katherine Fleming-Dutra
Sarah Meyer
Susan Goldstein
Mary Chamberland
Elisha Hall
Julianne Gee
Valerie Morelli
JoEllen WolickiHeather Scobie
Ruth Link - Gelles
Megan Lindley
Sierra Scarbrough
Jefferson Jones
Aron Hall
Barbara Mahon
Data Analytics and Visualization Task Force
Coronavirus and other Respiratory Viruses Division
National Center for Immunization and Respiratory
D
iseasesAcknowledgments
Question for ACIP
30Transition to bivalent primary series can only occur after FDA regulatory action
an
d updates to CDC recommendations
What are ACIP thoughts on a tr ansition of the mRNA COVID- 19 vaccine primary
series from monovalent (original) to bivalent (original plus Omicron BA.4/5)?
Note : “Monovalent” and “bivalent” designations are based on the currently authorized products.
For future vaccines, focus would be harmonization of products across primary series and booster doses.
For more information, contact CDC
1-800-CDC- INFO (232- 4636)
TTY:  1 -888-232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Thank you
Comparing monovalent and bivalent vaccines
Antibody data
1. https://www.biorxiv.org/content/10.1101/2022.10.22.513349v1.full.pdf
2. https://www.nejm.org/doi/full/10.1056/NEJMc2213948
3. https://www.nejm.org/doi/full/10.1056/NEJMc2214314
4. https://www.biorxiv.org/content/10.1101/2022.10.31.514636v1
5. https://www.nature.com/articles/s41591 -022-02162 -x
32Pseudovirus neutralization assayBivalent BA.4/BA.5
N=19Monovalent
N=21Ratio
Ancestral SARS -CoV -2 antibody titers (ID50) 8488 12054 0.70
BA.4/BA.5 neutralizing antibody titers (ID50) 1649 1366 1.2
Pseudovirus neutralization assayBivalent BA.4/BA.5
N=15Monovalent
N=18Ratio
Ancestral SARS -CoV -2 antibody titers (ID50) 40575 21507 1.89
BA.4/BA.5 neutralizing antibody titers (ID50) 3693 2829 1.31
Live virus neutralization assayBivalent BA.4/BA.5
N=12Monovalent
N=12Ratio
Ancestral SARS -CoV -2 antibody titers (ID50) 2312 1812 1.27
BA.5 neutralizing antibody titers (ID50) 576 142 4.06
Live virus neutralization assayBivalent BA.4/BA.5
WITH infection
N=23Monovalent
N=25Ratio
Ancestral SARS -CoV -2 antibody titers (ID50) 5776 1533 3.77
BA.4/BA.5 neutralizing antibody titers (ID50) 1558 95 16.4
XBB.1 neutralizing antibody titers (ID50) 103 15 8.58Wang, et al1
Collier, et al2
Davis -Gardner, et al4
Kurhade , et al5Pseudovirus neutralization assayBivalent BA.4/BA.5
N=15Monovalent
N=18Ratio
Ancestral SARS -CoV -2 antibody titers (ID50) 40515 21507 1.89
XBB.1 neutralizing antibody titers (ID50) 170 175 0.97Miller, et al3References for data:
Live virus neutralization assayBivalent BA.4/BA.5
Without infection
N=29Monovalent
N=25Ratio
Ancestral SARS -CoV -2 antibody titers (ID50) 3620 1533 2.36
BA.4/BA.5 neutralizing antibody titers (ID50) 298 95 3.14
XBB.1 neutralizing antibody titers (ID50) 35 15 2.33Antibody titers measured 24 -26 days after vaccine
Antibody titers measured ~21 days post- dose for bivalent and ~32 days post- dose for monovalent group
Timing post -vaccine differed (monovalent: 70 -100 days post vaccine; bivalent: 16 -42 days post vaccine) Antibody titers measured ~21 days post- dose for bivalent and ~32 days post- dose for monovalent group
Antibody titers measured at different time points (monovalent: 23 -94 days post vaccine; bivalent: 14 -32 days post vaccine)

Summary: cdc.gov/coronavirus Considerations for Bivalent Primary Series  Sara Oliver, MD, MSPH ACIP MeetingFebruary 24, 2023 Does ACIP support h armonizing the vaccine strain composition for mRNA COVID- 19  vaccines across both primary series and booster doses: Changing the primary series from monovalent (Original) to bivalent (Original plus Omicron  BA.4/5) for all ages?Question for consideration 2Mono- valent Mono- valent BivalentPeople ages 6 months and older* Bivalent Bivalent BivalentPeople ages…


COVID 09 Wallace 508

Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Diseases
Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Benefit and risk assessment for COVID -19 vaccines
Megan Wallace, DrPH, MPH
Benefit -risk assessment
2Benefits of COVID- 19 vaccine by age for primary series
Incremental benefits of COVID- 19 vaccine by age and time since last dose for
bivalent booster dose
–Sensitivity analyses model high and low points in the pandemic
Benefit -risk assessment for bivalent booster dose
–Focused on ages 12 -17 years and 18- 49 years
Methods for benefit assessment
3Benefits –Calculated per 1 million primary series or bivalent booster doses
Hospitalization rates1: December 2022 COVID -19-associated hospitalization rate among persons
aged 5 –11, 12–17, 18– 49, 50– 65, 65+ years, by vaccination status, from COVID-NET
–Sensitivity analyses model high and low points in the pandemic
Time horizon2: 6 months
Vaccine Effectiveness : VE estimates from VISION3with assumption of waning of effectiveness
by 10% each month starting after month 2
–VE of primary series based on absolute VE for bivalent dose4
–VE of bivalent booster dose based on relative VE by interval from last monovalent dose to
bivalent5
1https://covid.cdc.gov/covid -data -tracker/#covidnet- hospitalizations -vaccination. Rates among unvaccinated used for primary serie s assessment. Rates among those vaccinated with
monovalent doses only used for bivalent booster dose assessment.
2Period over which benefits of bivalent vaccination accrue
3https://www.cdc.gov/mmwr/volumes/71/wr/mm715152e1.htm?s_cid=mm715152e1_w.
4Absolute VE of bivalent booster dose (57%) used as the estimated primary series VE. Absolute VE from the bivalent booster was used as an estimate of primary series VE because current VE of
monovalent primary series is unknown.
5Relative VE of bivalent booster dose used in booster dose assessment (5 -7 month interval: 38%; 8- 10 month interval: 42%; 11+ mon th interval 45%). Relative VE for ED/UC visit was used for 2 -4
month interval (31%) because VE against hospitalization was not available
Monthly age-adjusted rates of COVID-19-associated hospitalization
by vaccination status in patients ≥ 18 years, COVID-NET
https://covid.cdc.gov/covid -data -tracker/#covidnet- hospitalizations -vaccination
4Age group Rate per 100,000
persons
5-11 Years 2.13
12-17 Years 2.66
18-49 Years 12.89
50-64 Years 27.48
≥ 65 Years 121.10December 2022 hospitalization rates per
100,000 vaccinated persons with no
bivalent booster by age group, COVID- NET

Estimated COVID -19-associated hospitalizations prevented over 6
months for every million mRNA COVID-19 primary series given
248
944
2465
5033
15978
0 2000 4000 6000 8000 10000 12000 14000 16000 18000COVID -19-associated hospitalizations p revented over 6 months per m illion doses by age group
Based on hospitalization rates from December 2022
12 –17 years
18 –49 years
50 –64 years
≥ 65 years
55 –11 years
Estimated COVID -19 hospitalizations prevented over 6 months for
every million mRNA COVID -19 primary series and bivalent booster doses1
53
257
549
2419944
2465
5033
15978
0 2000 4000 6000 8000 10000 12000 14000 16000 18000COVID -19-associated hospitalizations p revented over 6 months per million
primary series or bivalent booster by age group
Based on hospitalization rates from December 2022
12 –17 years
18 –49 years
50 –64 years
≥ 65 years
1. Calculated assuming booster dose given ≥11 months from last monovalent vaccine dose 6
Estimated COVID -19 hospitalizations prevented over 6 months for
every million bivalent mRNA COVID -19 booster doses, by age group and
dose interval1
0 500 1000 1500 2000 2500 3000COVID -19-associated hospitalizations p revented over 6 months per million doses given in
2 –4 month interval, 5 –7 month interval, 8 –10 month interval, ≥11 month interval
Based on hospitalization rates from December 2022
12 –17 years
18 –49 years
50 –64 years
≥ 65 years
7 1Interval refers to the time between the most recent monovalent dose and a bivalent dose.
Monthly age -adjusted rates of COVID -19-associated hospitalization
by vaccination status in patients 12 – 17 years, COVID -NET
https://covid.cdc.gov/covid -data -tracker/#covidnet- hospitalizations -vaccinationHigh
LowRecent
8

Estimated COVID -19 hospitalizations prevented over 6 months for
every million bivalent mRNA COVID -19 booster doses, 12 –17-year -olds
0 20 40 60 80 100 120 140 160COVID -19-associated hospitalizations p revented over 6 months per million
doses by low, recent , and high incidence1
2-5 month interval2
5-7 month interval2
8-10 month interval2
11+ month interval2
91Low incidence scenario uses hospitalization rate from March 2022, recent incidence scenario uses hospitalization rate from De cem ber 2022, and high incidence
scenario uses hospitalization rate from July 2022
2Interval refers to the time between the most recent monovalent dose and a bivalent dose.
Dosing intervals for monovalent booster and bivalent
booster, by age group
IZ Data Lake: Accessed 2/7/20230% 20% 40% 60% 80% 100%
12-17 year olds
18-49 year olds
2-4 month interval 5-7 month interval
8-10 month interval 11+ month interval0% 20% 40% 60% 80% 100%
12-17 year olds
18-49 year olds
2-4 month interval 5-7 month interval
8-10 month interval 11+ month intervalInterval between completion of the primary series
and monovalent boosterInterval between completion of the most recent
monovalent dose * and bivalent booster
* Primary series or monovalent boosterAmong adolescents who received a monovalent booster, nearly half received the
monovalent booster at an interval <8 months after their primary series
Over 90% of adolescents received a bivalent booster ≥8 months after their previous dose
Limited data to inform myocarditis risk after bivalent COVID- 19 vaccine booster dose
–
–
–Preliminary VSD myocarditis rates following b ivalent booster dose in adolescent and young adult
males lower than first monovalent boosters, but limited by small numbers of doses administered
Myocarditis risk lower wi th longer time between doses
Rates of myocarditis lower with extended interval between dose 1 and dose 2 for primary series1
Longer interval between doses for bivalent boosters, compared to monovalent boosters, may
also impact myocarditis rates
Most individuals with myocarditis/pericarditis have f ully recovered at follow-up2
The risk of adverse cardiac outcomes were 1 .8 –5.6 times higher after SARS -CoV-2
infection than after mRNA COVID-19 vaccination among males ages 12- 17 years3Myocarditis and COVID-19 vaccines
111 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2022-02-04/11-COVID -Moulia-508.pdf2https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/04-COVID -Kracalic-
508.pdf3https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm?s_cid=mm7114e1_w
VSD incidence rates of verified myocarditis or pericarditis in the 0 -7 days
after Pfizer-BioNTech vaccination in people 12 –39 years1
1Primary series and 1stmonovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; Source: Kristin Goddard, Kay laE. Hanson, Ned Lewis,
et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the United States .Ann Intern Med. [Epub 4 October
2022]. doi: 10.7326/M22- 2274Dose 2 Primary Series
Pfizer -BioNTech1stMonovalent Booster Dose
Pfizer -BioNTechBivalent Booster Dose
Pfizer -BioNTech
Age & Sex Cases Dose 2
TotalIncidence rate/ million doses (95% CI)Cases 1
stBooster
TotalIncidence rate/ million doses (95% CI)Cases Bivalent Booster TotalIncidence rate/ million doses(95% CI)
12-17 Years
MalesFemales456308,046311,247146.1 (106.6 – 195.5)
19.3 (7.1 – 42.0)142129,487139,118108.1 (59.1 –181.4)
14.4 (1.7 – 51.9)0048,06649,7250.0 (0.0 – 62.3)0.0 (0.0 – 60.2)
18-29 Years
MalesFemales272331,889400,32181.4 (53.6 –118.4)
5.0 (0.6 – 18.0)71166,973240,22641.9 (16.9 – 86.4)
4.2 (0.1 – 23.2)1050,68780,21119.7 (0.5 – 53.1)
0.0 (0.0 – 37.3)
30-39 Years
MalesFemales53341,527410,71314.6 (4.8 – 34.2)
7.3 (1.5 – 21.3)31197,554268,41215.2 (3.1 – 44.4)
3.7 (0.1 – 20.8)0082,191115,0140.0 (0.0 – 36.4)0.0 (0.0 – 26.0)
12
VSD incidence rates of verified myocarditis or pericarditis in the 0 –7 days
after Moderna vaccination in people ages 18 –39 years1
1Primary series and 1st monovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; sourc e: Goddard K, et al. Incidence of Myocarditis/Pericarditis
Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the United States .Ann Intern Med. 2022;175:1169- 1771.Dose 2 primary series
Moderna1stmonovalent booster dose
ModernaBivalent booster dose
Moderna
Age/sex CasesDose 2
totalIncidence rate/
million doses
(95% CI)Cases1stbooster
totalIncidence rate/
million doses
(95% CI)CasesBivalent
booster
totalIncidence rate/
million doses
(95% CI)
18–29 years
MalesFemales19
0195,809
243,56097.0 (58.4 – 151.5)
0.0 (0.0 – 12.3)71109,337156,70764.0 (25.7 – 131.9)
6.4 (0.2 – 35.6)0
018,49929,5610.0 (0.0 –161.9)
0.0 (0.0 –101.3)
30–39 yearsMalesFemales8
1216,583259,78036.9 (15.9 – 72.8)
3.9 (0.1 – 21.4)12149,468191,7656.7 (0.2 – 37.3)
10.4 (1.3 – 37.7)0
035,31847,6200.0 (0.0 –84.8)
0.0 (0.0 –62.9)
31 –136 hospitalizations prevented
9 –40 ICU admissions prevented
0 –1 death preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis
cases for every million bivalent mRNA COVID -19 booster doses:
12 –17-year -olds
Per million doses in 12 –17-year -olds over 6 months1
140 myocarditis2cases in 48,066 males with a bivalent booster
0 myocarditis2cases in 49,725 females with a bivalent booster
1Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8
2Based on preliminary Pfizer- BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0- 62) in males and 0 (95% CI: 0- 60) in females
17–75 hospitalizations prevented
5 –22 ICU admissions prevented
0 – 1death preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis cases for
every million bivalent mRNA COVID -19 booster doses: 12 –17-year -olds
Accounting for potential incidental SARS-CoV- 2 infections among hospitalized patients1
Per million doses in 12 –17-year -olds over 6 months2
150 myocarditis3cases in 48,066 males with a bivalent booster
0 myocarditis3cases in 49,725 females with a bivalent booster
1 Results were adjusted to account for potential incidental findings of SARS -CoV- 2 infection by multiplying the estimated hospital izations, ICU admissions, and deaths prevented by the estimated
percent of COVID -NET hospitalizations that are likely due to COVID- 19 among 12 –17-year -olds during on Omicron BA.5 predominant period (55%)
2 Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8
3Based on preliminary Pfizer- BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0- 62) in males and 0 (95% CI: 0- 60) in females
117 –376 hospitalizations prevented
21 –69 ICU admissions prevented
4 –11 deaths preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis
cases for every million bivalent mRNA COVID -19 booster doses:
18 –49-year -olds
Per million doses in 18 –49-year -olds over 6 months1
161 myocarditis2case in 186,695 males with a bivalent booster
0 myocarditis2cases in 272,406 females with a bivalent booster
1Ranges presented for benefits are based on the high and low incidence scenarios presented on slide 7
2Based on preliminary bivalent booster safety data from VSD among persons ages 18 -39 years. Among Pfizer -BioNTech recipients, rates per million doses were: 20 (95% CI: 1– 53) in males
ages 18 –29 years; 0 (95% CI: 0– 37) in females ages 18 –29 years; 0 (95% CI: 0– 36) in males ages 30 –39 years and 0 (95% CI: 0– 26) in females ages 30 –39 years. Among Moderna
recipients, rates per million doses were: 0 (95% CI: 0– 162) in males ages 18 –29 years; 0 (95% CI: 0– 101) in females ages 18 –29 years; 0 (95% CI: 0– 85) in males ages 30 –39 years and
0 (95% CI: 0– 63) in females ages 30 –39 years.
81 –259 hospitalizations prevented
15 –48 ICU admissions prevented
3 –8 deaths preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis cases for
every million bivalent mRNA COVID -19 booster doses: 18 –49-year -olds
Accounting for potential incidental SARS-CoV- 2 infections among hospitalized patients1
Per million doses in 18 –49-year -olds over 6 months2
171 myocarditis3case in 186,695 males with a bivalent booster
0 myocarditis3cases in 272,406 females with a bivalent booster
1 Results were adjusted to account for potential incidental findings of SARS -CoV- 2 infection by multiplying the estimated hospital izations, ICU admissions, and deaths prevented by the
estimated percent of COVID- NET hospitalizations that are likely due to COVID- 19 among 18 –49-year -olds during on Omicron BA.5 p redominant period (69%)
2 Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8
3Based on preliminary bivalent booster safety data from VSD among persons ages 18 -39 years. Among Pfizer -BioNTech recipients, rates per million doses were: 20 (95% CI: 1– 53) in males ages
18–29 years; 0 (95% CI: 0– 37) in females ages 18 –29 years; 0 (95% CI: 0– 36) in males ages 30 –39 years and 0 (95% CI: 0– 26) in females ages 30 –39 years. Among Moderna recipients, rates
per million doses were: 0 (95% CI: 0– 162) in males ages 18 –29 years; 0 (95% CI: 0– 101) in females ages 18 –29 years; 0 (95% CI: 0– 85) in males ages 30 –39 years and
0 (95% CI: 0– 63) in females ages 30 –39 years.
18
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Benefits of vaccination may continue to accrue beyond time horizon used
Stable hospitalization rates were assumed for the duration of the time horizon
Unde
rlying complexity of vaccine histories and previous infections could not be
accounted forCOVID -NET hospitalization rates include hospitalizations for which COVID- 19 was not a
primary reason for admission
Current COVID -19 epidemiology, including hospitalization rates used in assessment,
reflects impact of both prior vaccination and prior infection
–Cannot account for possible future increases in COVID -19 hospitalization rates or new variant
My ocarditis rates following bivalent booster dose are uncertain. Studies are underway
to assess the long- term impact of vaccine- associated myocarditisLimitations
Benefits c ontinue to outweigh risks for primary series vaccination in all age groups
Benefits of bivalent booster dose vary by age, time since last dose, and COVID- 1 9 incidence
Risk of myocarditis after COVID- 1 9 vaccines likely reduced by longer interval since last dose
–Additional data can better define risk after bivalent vaccines, but current data encouraging
Changes in COVID-19 hos pitalization rates would impact the benefit assessment
Additional b enefits of COVID-19 vaccines unable to be quantified in benefit- risk assessment
–Likely prevention of post- COVID conditions, possible reduction in transmission, increased confidence
in social interactions
Benefit risk assessment will continue to be monitored as new data are available
Receipt of primary series c ontinues to be important in all ages
Boosters r emain an important option to improve protection against severe COVID- 19,
especially for higher -risk populations
19Summary of benefit-risk balance for bivalent mRNA COVID -19 vaccination
VEaP Team
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–––Da
ni Moulia
Sara OliverEvelyn TwentymanKatherine Fleming -Dutra
R
uth Link-Gelles
C
OVID -NET
–Chris Taylor
ISO––Eric WeintraubTom ShimabukuroAcknowledgements
For more information, contact CDC
1-800-CDC- INFO (232- 4636)
TTY:  1 -888-232-6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.
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any use by other CDC CIOs or any external audiences.
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