02 su hep b 508

A Review of the Safety of Hepatitis B Birth Dose
Vaccination
John Su
Acting Director
Immunization Safety Office
Centers for Disease Control and Prevention
September 18, 2025National Center for Emerging and Zoonotic Infectious Diseases
Request to CDC from ACIP Chair
Safety data for HepB administration within 24 hours of birth from CDC’s
Vaccine Safety Datalink and from FDA’s Biologics Effectiveness and Safety
System. Include (i) mild and serious adverse events; (ii) all cause morbidity and mortality; (iii) short term and long -term safety; (iv) both
specific outcomes of pre- determined concern as well as results from data
mining where large numbers of potential adverse events are evaluated; and (v) both combined results and results stratified by sex. If some of these types of safety studies are unavailable, please mention that.
2
Rapid systematic review of hepatitis B post- licensure
safety data
•Key question:
-What is the safety of the hepatitis B
vaccine administered within the first 30 days of life?
•Conducted a new rapid systematic review of published literature
-Search conducted July 31, 2025 with no
date restrictions for publications
•Electronic databases searched:
-MEDLINE
-EMBASE
-CINAHL
-Cochrane
* Population, Intervention, Comparator, and Outcome, Setting, Time frameworkPI/ECO(ST)
ELEMENT*Description for this Review
Population Neonates, Newborns, Infants
Intervention or ExposureHepatitis B vaccine administration within the
first 30 days of birth:
HepB, HepB -BD, HBV, Engerix -B, Recombivax
HB
Comparator (if
applicable)Any or none
Outcome(s) Adverse events
Adverse outcomesSafety outcomesSide effects
Reaction
Adverse reactionAdverse effectSerious adverse event
Setting Any
Time Frame Any publication years
Any duration of follow up  Search Strategy
3
Rapid systematic review:
Inclusion/exclusion criteria
Inclusion Criteria Exclusion Criteria
•Newborn infants receiving a hepatitis B vaccine
at birth (i.e., ≤30 days old at dose 1)•Non -English language articles
•Animal studies
•Randomized control trial (RCT)
•Observational studies
•Case series ≥ 10
•Data from surveillance systems•Any population that did not receive hepatitis B vaccine at ≤30 days old at dose 1
•N < 10
Outcomes include any of the following:•Safety
•Adverse events
•Serious adverse events
•Side effects•Clinical trial protocols
•(e.g., clinicaltrials.gov, trialsearch.gov identified in the citation)
•Conference abstracts/ posters
•Conference proceedings in title or journal title
•Title starts with a number
•Poster
4
Results
Results of rapid systematic review of hepatitis B safety
administered in the first 30 days of life
Identification Screening IncludedStudies from databases/registers (n = 1916)
MEDLINE (n = 1916)Studies  removed (n = 9)
Duplicates identified manually (n = 9)
Duplicates identified by Covidence (n = 0)
Marked as ineligible by automation tools (n = 0)
Other reasons (n = 0)
Studies screened  at title & abstract (n = 1907) Studies excluded  at title & abstract (n = 1678)
Did not meet inclusion criteria (n = 1678)
Studies assessed for eligibility  at full text
review          (n = 229)    Studies excluded  at full text review (n = 158)
No intervention of interest (n = 48)
No outcome of interest (n = 30)
Not relevant to key question (n = 7)No population of interest (n = 51)Not available in English (n = 5)
Insufficient methodologic reporting (i.e., poster, abstract, letter to editor) (n = 8)
No primary data collection or secondary data not systematically collected (n = 8)No full text available (n = 0)
Studies assessed for  outcomes stratified by hepatitis
B birth dose  (n = 71)    Studies excluded (n = 51)
Outcome or population not stratified by h epatitis B birth dose (n = 47)
Systematic reviews/meta -analyses (n = 4)
Studies extracted for h epatitis B birth dose (n = 20)
6
Summary of publications meeting search criteria
•Total of 20 studies of hepatitis B
vaccine administration within 30 days of life included in review
-Five studies defined birth dose as hepatitis
B vaccine administered within 24 hours of
birth
•VSD: 1 study
-Four studies used other terms to define
hepatitis B vaccine birth dose
•Terms used:  Given at birth, Birth dose,
within 120 hours of birth
•One study stated that 85% received hepatitis B on date of birth, none received the vaccine beyond 8 days of life
•VSD: 1 studyCharacteristic # of Studies
Study design RCT 5
Cohort 7
Surveillance report 2
Case control 4
Case series 1
Cross -sectional 1
Vaccine
administeredEngerix -B 5
Recombivax 1
Hepatitis B product not -
specified14
Timing of administration as noted in the paper≤ 24 hours 5
Within 8 days of birth 4
Within first month of life 11Study characteristics (N = 20)
7
Studies evaluating local reactions: Pain
Hepatitis B vaccination within 24 hours of birth (n = 1 study)
In one RCT, pain was reported for 7.7% of infants in the 5 days after Engerix -B vaccination.
Study Study Type Outcome Outcome Window Comparison groupsLocal reactions
Intervention Results %
(N)Comparison Results %
(N)
Yerushalmi 1997 RCT Pain with movement Within 5 days of vaccination Engerix -B vs BioHepB* 7.7 (4) 2.6 (4)
Yerushalmi 1997 RCT Pain with pressure Within 5 days of vaccination Engerix -B vs BioHepB* 7.7 (4) 1.3 (2)
Study Study Type Outcome Outcome Window Comparison groupsLocal reactions
Intervention Results %
(N) Comparison Results %
(N)
Greenberg 2002 RCT Pain or soreness Within 3 days of vaccinationEngerix -B vs DTaP -HepB, OPV,
and Hib at 2 months of age8.1 (NR);
0 (0) severe**35.7 (NR);
1.6 (NR) severe**,†
Lopez 2002 Cohort Pain or soreness Within 4 days of vaccinationEngerix -B only
(no comparison group)6.0 (7);
4.3 (5) severe§NA
Wood 2018 RCT Pain or soreness Within 2 days of vaccinationEngerix -B alone vs Engerix -B+
investigational acellular Pertussis
vaccine9.3 (14);
0 (0) severe¶19.7 (41);
0.5 (1) severe¶Hepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^
Pain or soreness within the 4 days after Engerix -B was reported for <10% of newborns; few were severe.
NA = not applicable; NR = not reported
*The hepatitis B vaccine BioHepB  is not approved for use in the United States
^Studies indicated hepatitis B administration at birth, within 120 hours of birth**Severe: soreness that caused crying when limb moved;
†Severe reported for any injection site; §Severe: not defined; ¶Severe: crying when limb moved/spontaneously painful or prevents daily activities8
Studies evaluating local reactions: Redness or erythema
Hepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^
Redness or erythema within 4 days after Engerix -B was reported for 8 -20% of newborns; none were severe.
StudyStudy
TypeOutcome Outcome Window Comparison groupsLocal reactions
Intervention Results % (N) Comparison Results % (N)
Greenberg 2002 RCTRedness or
erythemaWithin 3 days of vaccinationEngerix -B within 4 days of
birth  vs DTaP -HepB, OPV, and
Hib at 2 months of age8.8 (NR);
0 (0) severe**11.6 (NR);
0 (0) severe**,†
Lopez 2002 CohortRedness or
erythema Within 4 days of vaccinationEngerix -B only
(no comparison group)11.1 (13);
0 (0) severe**NA
Wood 2018 RCTRedness or
erythema Within 2 days of vaccinationEngerix -B alone vs Engerix -
Bwith an investigational
acellular Pertussis vaccine20.0 (30);
0 (0) severe§27.4 (57);
0 (0) severe§
NA = not applicable; NR = not reported
*The hepatitis B vaccine BioHepB  is not approved for use in the United States
^Studies indicated hepatitis B administration at birth, within 120 hours of birth
**Severe: diameter  >20 mm; †Severe reported for any injection site; §Severe: diameter ≥30 mmStudyStudy
TypeOutcome Outcome Window Comparison groupsLocal reactions
Intervention Results % (N) Comparison Results % (N)
Yerushalmi 1997 RCTRedness or
erythemaWithin 5 days of
vaccinationEngerix -B vs BioHepB* 0 (0) 0 (0)Hepatitis B vaccination within 24 hours of birth (n = 1 study)
In one RCT, redness or erythema was not reported in either comparison arm.
9
Studies evaluating local reactions: Swelling
Hepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^
Swelling within 4 days was reported in 0-4% for newborns who received Engerix -B; there were no severe
reports.
StudyStudy
TypeOutcome Outcome Window Comparison groupsLocal reactions
Intervention Results % (N) Comparison Results % (N)
Greenberg
2002RCT Swelling Within 3 days of
vaccinationEngerix -B vs DTaP -HepB, OPV, and
Hib at 2 months of age0 (0);
0 (0) severe**16.3 (NR);
3.1 (NR) severe**,†
Lopez
2002Cohort SwellingWithin 4 days of
vaccinationEngerix -B only
(no comparison group)4.3 (5);
0 (0) severe**NA
Wood 2018 RCT Swelling Within 2 days of
vaccinationEngerix -B alone vs Engerix -B+
investigational acellular Pertussis
vaccine  4.0 (6);
0 (0) severe§12.5 (26);
0 (0) severe§
NA = not applicable; NR = not reported
*The hepatitis B vaccine BioHepB  is not approved for use in the United States
^Studies indicated hepatitis B administration at birth, within 120 hours of birth
**Severe: diameter  >20 mm; †Severe reported for any injection site; §Severe: diameter ≥30 mmStudyStudy
TypeOutcome Outcome Window Comparison groupsLocal reactions
Intervention Results % (N) Comparison Results % (N)
Yerushalmi
1997RCT SwellingWithin 5 days of
vaccinationEngerix -B vs BioHepB* 7.7 (4) 2.0 (3)Hepatitis B vaccination within 24 hours of birth (n = 1 study)
In one RCT, swelling was reported for 7.7% of newborns in the days after they received Engerix -B.
10
Studies evaluating any local reactions
StudyStudy
TypeOutcome Outcome Window Comparison groupsLocal reactions
Intervention Results %
(N)Comparison Results % (N)
Bassily 1995 RCT Local side effects Within 1 week of vaccinationRecombivax at birth vs
Recombivax at 18 months 2.8 (5) 1.6 (3)
11Hepatitis B vaccination within 0-5 days  of birth (n = 1 study)
In one RCT, any local reaction* during the week of Recombivax was reported for 2.8% of newborns
*Local reaction: local soreness, temporary redness/induration at the injection site
Studies evaluating systemic reactions: Fever
StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactionsMeasure of
Association Intervention Results % (N)Comparison Results
% (N)
Bassily  1995 RCT FeverWithin 1 week of
vaccinationRecombivax at birth vs
Recombivax at 18 months5.6 (10) 2.1 (4) NR
Linder 1999 Cohort Fever, >37.5 °CWithin birth
hospitalizationHepatitis B vaccine vs No
Hepatitis B vaccine 1.2 (68) 0.5 (27) p = 0.001
0.9 (50) >38° C 0.5 (27) >38° C p = 0.05
Lewis 2001 Cohort FeverWithin first 21 days
of lifeHepatitis B vaccine  vs. No
Hepatitis B Vaccine0.8 (21) 1.1 (25)aRR§: 0.85 (95%CI:
0.6-1.1); p=0.28
Yerushalmi
1997RCT Fever, ≥38 °CWithin 5 days of
vaccinationEngerix -B vs BioHepB* 0 (0) 1.3 (2) NRHepatitis B vaccination within 24 hours of birth (n = 4 studies)
Fever in the days to weeks after hepatitis B vaccination was reported for 0 -5.6% of newborns
StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactionsMeasure of
Association
Intervention Results %
(N)Comparison Results %
(N)
Greenberg
2002RCT Fever, ≥38.0oCWithin 3 days of
vaccinationEngerix -B vs DTaP -HepB,
OPV, and Hib at 2 months
ofage5.9 (NR);
0 (NR) >39.5oC14.7 (NR);
0.8 (NR) >39.5oCNR
Wood 2018 RCT Fever, ≥38.0oCWithin 2 days of
vaccinationEngerix -B alone vs Engerix -B+
investigational
acellular Pertussis vaccine0.7 (1);
0 (0) ≥39.0oC0 (0);
0 (0) ≥39.0oCNR
Lopez 2002 Cohort Fever, ≥38.0oCWithin 4 days of
vaccinationEngerix -B only
(no comparison group)0.9 (1);
0.9 (1) >39.0oC axillary
or >39.5° C rectalNA NAHepatitis B vaccination within 0-5 days  of birth (n  =  3 studies)^
Fever within 4 days after Engerix -B vaccination was reported for 0 -5.9% of newborns; few were severe.
NA = not applicable; NR = not reported. * The hepatitis B vaccine BioHepB  is not approved for use in the United States.; ^Studies indicated hepatitis B administration at birth, within 120 hours of birth
§ Adjusted relative risk; Adjusted for maternal age, low Apgar at 1 minute, low Apgar at 5 minutes, maternal smoking, gestation  period and congenital heart disease status 12
Studies evaluating systemic reactions: anorexia or decreased appetite
StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactions
Intervention Results % (N) Comparison Results % (N)
Greenberg 2002 RCTAnorexia/Decreased
appetite Within 3 days of
vaccinationEngerix -B vs DTaP -HepB, OPV, and
Hib at 2 months of age14.0 (NR);
1.5 (NR) severe**25.6 (NR);
0.8 (NR) severe**
Lopez 2002 CohortAnorexia/Decreased
appetite Within 4 days of
vaccinationEngerix -B only
(no comparison group)2.6 (3);
1.7 (2) severe†NA
Wood 2018 RCTFeeding
issues/Decreased
appetite Within 2 days of
vaccinationEngerix -B alone vs Engerix -B+
investigational acellular Pertussis
vaccine16.5 (17);
1.0 (1) severe§12.7 (28);
0 (0) severe§
**Severe: prevents normal daily activities; †Severe: not defined; §Severe: prevents normal daily activities or requires significant medical interventionHepatitis B vaccination within 0-5 days  of birth ( n= 3 studies)^
Anorexia or decreased appetite was reported for 2.6 -16.5% of newborns after Engerix -B vaccination; there
were few severe reports.StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactions
Intervention Results %
(N)Comparison Results %
(N)
Yerushalmi 1997 RCT Anorexia/ decreased appetite Within 5 days of vaccination Engerix -B vs BioHepB* 0 (0) 2.0 (3)
NA = not applicable; NR = not reported
*The hepatitis B vaccine BioHepB  is not approved for use in the United States
^Studies indicated hepatitis B administration at birth, within 120 hours of birthHepatitis B vaccination within 24 hours of birth (n = 1 study)
In one RCT, anorexia or decreased appetite was not reported for newborns who received Engerix -B.
13
Studies evaluating systemics reactions:  Gastrointestinal (GI) symptoms
StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactions
Intervention Results % (N)Comparison
Results % (N)
Greenberg 2002 RCT DiarrheaWithin 3 days
ofvaccinationEngerix -B vs DTaP -HepB, OPV, and Hib
at 2 months ofage8.1 (NR);
0.7 (NR) severe**10.1 (NR);
0 (0) severe**
Wood 2018 RCT DiarrheaWithin 2 days
ofvaccinationEngerix -Balone vs Engerix -B+
investigational acellular Pertussis
vaccine11.7 (12);
0 (0) severe†17.2 (38);
0 (0) severe†
Greenberg 2002 RCT VomitingWithin 3 days of
vaccinationEngerix -B vs DTaP -HepB, OPV, and Hib
at 2 months ofage4.4 (NR);
0 (0) severe**7.8 (NR);
0 (0) severe**
Wood 2018 RCT VomitingWithin 2 days of
vaccinationEngerix -Balone vs Engerix -B+
investigational acellular Pertussis
vaccine22.3 (23);
0 (0) severe†20.4 (45);
0 (0) severe†
NR = not reported
*The hepatitis B vaccine BioHepB  is not approved for use in the United States
^Studies indicated hepatitis B administration at birth, within 120 hours of birth**Severe: prevents normal daily activities;
†Severe: prevents normal daily activities or requires significant medical interventionHepatitis B vaccination within 0-5 days  of birth (n = 2 studies)^
GI symptoms were reported for 0 -22% of newborns who received Engerix -B; there were no reports.StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactions
Intervention Results %
(N)Comparison Results %
(N)
Yerushalmi 1997 RCT Diarrhea or vomitingWithin 5 days of
vaccinationEngerix -B vs BioHepB* 0 (0) 0.6 (1)Hepatitis B vaccination within 24 hours of birth (n = 1 study)
In one RCT, diarrhea or vomiting was not reported for newborns who received Engerix -B
14
Hepatitis B vaccination within 24 hours of birth (n = 1 study)
In one RCT, irritability or fussiness was reported for 11.5% of infants in the days after Engerix -B vaccination.
StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactions
Intervention Results %
(N)Comparison Results %
(N)
Greenberg 2002 RCT Irritability or fussinessWithin 3 days of
vaccinationEngerix -B vs DTaP -HepB, OPV, and Hib
at 2 months of age22.1 (NR)
0.7 (NR) severe**54.3 (NR);
3.9 (NR) severe**
Wood 2018 RCT Irritability or fussinessWithin 2 days of
vaccinationEngerix -B alone vs Engerix -B+
investigational acellular Pertussis
vaccine20.4 (21);
1.0 (1) severe†24.4 (54);
0.9 (2) severe†
Lopez 2002 Cohort Irritability or fussinessWithin 4 days of
vaccinationEngerix -B only
(no comparison group)2.6 (3);
1.7 (2) severe§NA
Greenberg 2002 RCT Unusual cryingWithin 3 days of
vaccinationEngerix -B vs DTaP -HepB, OPV, and Hib
at 2 months ofage1.5 (NR);
0 (0) severe**3.1 (NR);
0.8 (NR) severe**
NA = not applicable; NR = not reported
*The hepatitis B vaccine BioHepB  is not approved for use in the United States
^Studies indicated hepatitis B administration at birth, within 120 hours of birth
**Severe: prevents normal daily activities; †Severe: prevents normal daily activities or requires significant medical intervention ; §Severe: not definedHepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^
Irritability, fussiness, or crying was reported for 1.5 -22.1% of newborns who received Engerix -B; there were
few severe reports.StudyStudy
TypeOutcome Outcome Window Comparison groupsSystemic reactions
Intervention Results %
(N)Comparison Results %
(N)
Yerushalmi 1997 RCT Irritability or fussinessWithin 5 days of
vaccinationEngerix -B vs BioHepB* 11.5 (6) 3.3 (5)
15Studies evaluating systemic reactions:  Irritability or fussiness or crying
Studies evaluating systemic reactions: Sleep disturbance
StudyStudy
TypeOutcomeOutcome
WindowComparison groupsSystemic reactions
Intervention Results % (N) Comparison Results % (N)
Greenberg
2002RCTDrowsiness or
sleeping moreWithin 3 days
of vaccinationEngerix -Bvs DTaP -HepB, OPV, and Hib at 2
months of age 32.4 (NR);
2.9 (NR) severe*40.3 (NR);
0.8 (NR) severe*
Wood
2018RCTDrowsiness or
sleeping moreWithin 2 days
of vaccinationEngerix -B alone vs Engerix -B+
investigational acellular Pertussis vaccine 27.2 (28);
1.0 (1) severe§17.6 (39);
0.5 (1) severe§
Lopez
2002CohortDrowsiness or
sleeping moreWithin 4 days
of vaccinationEngerix -B only
(no comparison group)5.1 (6);
0.9 (1) severe†NA
Greenberg RCTRestlessness or
sleeping lessWithin 3 days
of vaccinationEngerix -B vs DTaP -HepB, OPV, and Hib at 2
months ofage16.9 (NR);
1.5 (NR) severe*26.4 (NR);
0.8 (NR) severe*
Wood
2018RCTRestlessness or
sleeping lessWithin 2 days
of vaccinationEngerix -B alone vs Engerix -
B+investigational acellular Pertussis vaccine31.1 (32);
2.9 (3) severe§22.2 (49);
0.9 (2) severe§
NA = not applicable; NR = not reported
^Studies indicated hepatitis B administration at birth, within 120 hours of birth
*Severe: prevents normal daily activities; †Severe: not defined; §Severe: prevents normal daily activities or requires significant medical interventionThere were no studies evaluating sleep disturbance for children who received hepatitis B vaccine within
24 hours of birth
Hepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^
Sleep disturbances were reported for 5.1 -32.4% of newborns who received Engerix -B; there were few severe
reports .
16
Studies evaluating allergic reaction or atopy
StudyStudy
TypeOutcome Outcome Window Comparison groupsAllergic Reaction
Measure of
Association Intervention
Results % (N)Comparison
Results % (N)
Lewis 2001 Cohort Allergic reaction Within 3 weeks of life Hepatitis B vaccine vs No hepatitis B vaccine <0.1 (1) <0.1 (1)RR†: 0.87
(95% CI: 0.05- 13.8);
p=0.99Hepatitis B vaccination within 24 hours of birth (n = 1)
There were no differences between vaccinated and unvaccinated newborns in the proportion of those
who received care for an allergic reaction in the first 21 days of life.
†Relative risk 17There were no studies evaluating allergic reaction or atopy for newborns who received hepatitis B vaccine within
0-5 days  of birth
Studies evaluating infections
StudyStudy
TypeOutcome Outcome Window Comparison groupsNumber of cultures
Measure of
Association Intervention
Results % (N)Comparison Results %
(N)
Lewis 2001 CohortBlood or CSF culture
performedWithin 3 weeks of lifeHepatitis B vaccine vs no
hepatitis B vaccine4.6 (126) 8.6 (203)RR: 0.71 (95% CI: 0.63-
0.80); p<0.001
Lewis 2001 CohortBlood or CSF culture
positiveWithin 3 weeks of lifeHepatitis B vaccine vs no
hepatitis B vaccine 0.3 (7) 0.7 (16)RR: 0.57 (95% CI: 0.35-
0.94); p=0.027Hepatitis B vaccination within 24 hours of birth (n = 1 )
Newborns vaccinated against hepatitis B were less likely to be evaluated for possible sepsis and less
likely to have a positive blood or cerebrospinal fluid (CSF) culture.
†Relative risk 18There were no studies evaluating infection for newborns who received hepatitis B vaccine within 0-5
days  of birth
Studies evaluating other adverse events
StudyStudy
TypeOutcome Outcome Window Comparison groupsAdverse Event
Measure of
Association Intervention
Results % (N)Comparison Results %
(N)
Lewis 2001 Cohort Seizures Within 3 weeks of lifeHepatitis B vaccine vs no
hepatitis B vaccine0.04 (1) 0.17 (4)RR†: 0.22 (95% CI:
0.02- 1.9), p=0.19
Lewis 2001 CohortNeurological
disorders other than
seizuresWithin 3 weeks of lifeHepatitis B vaccine vs no
hepatitis B vaccine0.15 (4) 0.08 (2)RR†: 1.7 (95% CI: 0.3-
9.4), p=0.69
Morgan
2025*CohortBPD in preterm
infants born at <29
gestational weeks36 weeks postmenstrual
age**Hepatitis B vaccine vs no
Hepatitis B vaccine50.7 (155) 61.9 (317)aRR§: 0.83 (95% CI:
0.68- 1.0)Hepatitis B vaccination within 24 hours of birth (n = 3)
Hepatitis B vaccination does not appear to affect risk of seizures or neurological disorders. It may have a
slight protective effect on bronchopulmonary dysplasia (BPD) among preterm infants.
StudyStudy
TypeOutcome Outcome Window Comparison groupsAdverse Event
Measure of
Association Intervention
Results % (N)Comparison Results %
(N)
Lopez 2002 Cohort Serious adverse eventWithin 30 days of
vaccinationEngerix -B only
(no comparison)0.9 (1) NA NAHepatitis B vaccination within 0-5 days  of birth (n =1)
There was one report of cough requiring hospitalization 37 days after Engerix -B birth dose vaccination.
19NA = not applicable; *Extremely preterm infants <29 weeks gestation; †Relative risk
§ Adjusted relative risk; Adjusted for maternal age, low Apgar at 1 minute, low Apgar at 5 minutes, maternal smoking, gestation  period and congenital heart disease status (unadjusted RR: 0.81; 95% CI:
0.67- 0.98); ** A diagnosis of BPD was evaluated for all infants once they reached 36 weeks postmenstrual age
Studies evaluating all cause mortality
Study Study Type OutcomeOutcome
WindowComparison groupsDeathsMeasure of
AssociationIntervention
Results % (N)Comparison Results
% (N)
Morgan
2025*CohortAll-cause mortality in
preterm infants born at
<29 gestational weeksWithin 3
months of lifeHepatitis B Vaccine vs No Hepatitis
BVaccine2.3 (7) † 2.7 (14)aRR§: 1.13
(95%CI: 0.42-
2.81)Hepatitis B vaccination within 24 hours of birth (n = 1 )
There were no differences in all cause-mortality within 3 months of life among preterm infants who
received hepatitis B vaccine within 24 hours of birth and those who did not.
StudyStudy
TypeOutcomeOutcome
WindowComparison groupsNeonatal deathsMeasure of
AssociationIntervention Results
% (N)Comparison Results
% (N)
Eriksen 2004 CohortExpected neonatal
deathWithin 29 days of
vaccinationHepatitis B Vaccine vs No Hepatitis
BVaccine69 (50) 65 (128) p=0.6
Eriksen 2004 CohortUnexpected neonatal
deathWithin 29 days of
vaccinationHepatitis B Vaccine vs No Hepatitis
BVaccine31 (22) 35 (68) p=0.6
Eriksen 2004 CohortUnexpected neonatal
death from SIDSWithin 29 days of
vaccinationHepatitis B Vaccine vs No Hepatitis
BVaccine3.3 per 100,000
births3.3 per 100,000
birthsp=0.99
Greenberg  2
002RCT All-cause mortalityWithin 7 months
ofvaccinationEngerix -B vs DTaP -HepB , OPV, and Hib 0 (0) 0 (0) NAHepatitis B vaccination within 0-8 days  of birth (n = 2 studies)^
One cohort suggested no difference in expected or unexpected deaths, deaths due to SIDS, among newborns who received hepatitis B vaccine and those who did not. There were no deaths reported in one RCT.
NA = not applicable.
^ Greenberg indicated hepatitis B administration occurred within 4 days (median 1 day) of birth. Eriksen stated that 85% receive d HBV on date of birth, none received the vaccine beyond 8 days of life
*Extremely preterm infants <29 weeks gestation. † Infants may have received other vaccines within the 3 -month period. The cause of death for most of these infants appeared to be unrelated to the disease
and multifactorial in nature, with most deaths probably a result of prematurity or congenital abnormalities (i.e. preceding t he HBV vaccination). § Adjusted relative risk; Adjusted for maternal age, low Apgar
at 1 minute, low Apgar at 5 minutes, maternal smoking, gestation period and congenital heart disease status (unadjusted RR: 0 .83; 95% CI: 0.32– 2.00)20
Lack of association between hepatitis B birth immunization and
neonatal death: A population- based study from the Vaccine Safety
Datalink Project
•Methods:
•Birth cohort was defined from Southern and Northern California Kaiser Permanente Health Plans of more than
350,000 live births from 1993 –  1998
•All deaths were ascertained occurring under 29 days of age
•Expected deaths:
•Deaths among extremely low birth weight (ELBW) neonates (defined as birth weight 600 g or extremely preterm 24
weeks of gestation)
•Death because of lethal congenital anomalies or other genetic conditions
•Deaths from multiple cardiac or multiple (individually) nonlethal conditions
•Potentially fatal conditions present at or within several hours of birth, such as neonatal sepsis or severe respiratory distress syndrome
.
•Unexpected deaths: No apparent preexisting medical conditions
•The proportion of deaths among birth hepatitis b vaccinated and unvaccinated were compared
•Medical record review conducted
•Results:
•1,363 neonatal deaths identified during the study period
•66% of the entire birth cohort received hepatitis B vaccine at birth
•Among all deaths, only 5% (72) neonates who died received hepatitis vaccine at birth
•No significant difference in the proportion of hepatitis B vaccinated to unvaccinated dying of unexpected causes
•Conclusion: A relationship between hepatitis B and neonatal death was not identified
Eriksen EM, Perlman JA, Miller A, et al. Lack of association between hepatitis B birth immunization and neonatal death: A pop ulation -based study from the Vaccine Safety Datalink Project. Pediatr  Infect Dis J .
July 2004;23(7):656- 661. doi:10.1097/01.inf.0000130953.08946.d0
Limitation of rapid systematic review
22•Not all papers specified the exact timing of hepatitis B administration
•There were variable approaches to data collection, data analysis, and
reporting in the studies
•Primary end points included short -term outcomes (e.g., <30 days) such as
reactogenicity and mortality
•Studies that met the inclusion criteria of hepatitis B administration within 24 hours or at birth did not include long -term outcomes
•Studies that did not meet the inclusion criteria of hepatitis b administration within 24
hours or at birth do include long -term safety outcomes (e.g., > 30 days)
Summary of evidence
•The safety data available for hepatitis B vaccine administered at birth did not
identify an increased risk:
-Allergic reaction
-All-cause mortality
-Expected, or unexpected deaths or deaths due to sudden infant death syndrome (SIDS)
-Seizures or neurologic disease other than seizures
•Compared to those who did not receive a hepatitis B vaccine administered at birth, there was a reduction in risk among those who received hepatitis B vaccine for:
-An invasive diagnostic procedure (blood and CSF cultures) and a reduction in positive
cultures
-Bronchopulmonary dysplasia
•Reactogenicity within 1 week of vaccination varied by study.
23
References (1 of 2)
24Studies that defined birth dose as hepatitis B vaccine administered within 24 hours of birth
• Bassily  S, Kotkat A, Gray G, et al. Comparative study of the immunogenicity and safety of two dosing schedules of hepatitis B vaccine in neonat es. Am J Trop Med Hyg . Oct
1995;53(4):419- 22. doi:10.4269/ajtmh.1995.53.419
• Lewis E, Shinefield  HR, Woodruff BA, et al. Safety of neonatal hepatitis B vaccine administration. Pediatr Infect Dis J . Nov 2001;20(11):1049- 54. doi:10.1097/00006454-
200111000- 00009
• Linder N, Raz M, Reichman B, et al. Unexplained fever in neonates may be associated with hepatitis B vaccine. Archives of Disease in Childhood: Fetal and Neonatal Edition .
1999;81(3):F206- F207. doi:10.1136/fn.81.3.F206
• Morgan HJ, Nold MF, Kattan GS, et al. Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a co hort study, Australia. Vaccination contre  l'hepatite
B de prematures  et risque  de dysplasie  bronchopulmonaire : etude de cohorte  en Australie , Vacunacion  contra la hepatitis B en neonatos  prematuros  y riesgo  de displasia
broncopulmonar : estudio  de cohortes  en Australia. Bull World Health Organ . 2025;103(3):187- 193. doi:10.2471/BLT.24.291683
• Yerushalmi B, Raz R, Blondheim O, Shumov  E, Koren R, Dagan R. Safety and immunogenicity of a novel mammalian cell -derived recombinant hepatitis B vaccine containing Pre-
S1 and Pre -S2 antigens in neonates. Pediatr  Infect Dis J . Jun 1997;16(6):587- 92. doi:10.1097/00006454- 199706000- 00009
Studies that indicated hepatitis B vaccine administered within 0 -8 days of birth
• Eriksen EM, Perlman JA, Miller A, et al. Lack of association between hepatitis B birth immunization and neonatal death: A popula tion -based study from the Vaccine Safety
Datalink Project. Pediatr  Infect Dis J . July 2004;23(7):656- 661. doi:10.1097/01.inf.0000130953.08946.d0
• Greenberg DP, Wong VK, Partridge S, Howe BJ, Ward JI. Safety and immunogenicity of a combination diphtheria -tetanus toxoids -acel lular pertussis -hepatitis B vaccine
administered at two, four and six months of age compared with monovalent hepatitis B vaccine administered at birth, one month  and six months of age. Pediatr  Infect Dis J . Aug
2002;21(8):769- 77. doi:10.1097/00006454- 200208000- 00014
• Lopez P, Rubiano L, del Pilar Rubio M, David MP, Safary A. Immunogenicity and reactogenicity of DTPw -HB/Hib vaccine administered to colombian  infants after a birth dose of
hepatitis B vaccine. Clinical Trial. Expert Rev Vaccines. Oct 2002;1(3):277- 83. doi:10.1586/14760584.1.3.277
• Wood N, Nolan T, Marshall H, et al. Immunogenicity and Safety of Monovalent Acellular Pertussis Vaccine at Birth: A Randomize d Clinical Trial. Jama, Pediatr . 11 01
2018;172(11):1045- 1052. doi:10.1001/jamapediatrics.2018.2349
References (2 of 2)
25Studies that indicated hepatitis B vaccine administered within >8 days of birth and within first month of life
•Gallagher CM, Goodman MS. Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997 -2002. Journal of Toxicology and Environmental Health -  Part A: Current Issues .
January 2010;73(24):1665- 1677. doi:10.1080/15287394.2010.519317
•Geier DA, Hooker BS, Kern JK, King PG, Sykes LK, Geier MR. A two -phase study evaluating the relationship between Thimerosal -cont aining vaccine administration and the risk for an autism
spectrum disorder diagnosis in the United States. Transl  Neurodegener . Dec 19 2013;2(1):25. doi:10.1186/2047 -9158- 2-25
•Geier DA, Kern JK, Hooker BS, et al. Thimerosal exposure and increased risk for diagnosed tic disorder in the United States: A case-control study. Interdisciplinary Toxicology . 01 Jun
2015;8(2):68- 76. doi:10.1515/intox -2015- 0011
•Geier DA, Kern JK, Hooker BS, King PG, Sykes LK, Geier MR. A longitudinal cohort study of the relationship between Thimerosal -containing hepatitis B vaccination and specific delays
indevelopment in the United States: Assessment of attributable risk and lifetime care costs. Journal of Epidemiology and Global Health. 01 Jun 2016;6(2):105-
118. doi:10.1016/j.jegh.2015.06.002
•Geier DA, Kern JK, Homme KG, Geier MR. Thimerosal exposure and disturbance of emotions specific to childhood and adolescence:  A case -control study in the Vaccine Safety Datalink
(VSD) database. Brain Injury. 28 Jan 2017;31(2):272- 278. doi:10.1080/02699052.2016.1250950
•Geier DA, Kern JK, Geier MR. Premature puberty and thimerosal -containing Hepatitis B vaccination: A case -control study in the va ccine safety datalink. Toxics. 15 Nov 2018;6(4) (no
pagination)67. doi:10.3390/toxics6040067
•Haber P, Moro PL, Ng C, et al. Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccin e Adverse Event Reporting System (VAERS), 2005 -2015. Historical
Article. Vaccine. 01 25 2018;36(4):559- 564. doi:10.1016/j.vaccine.2017.11.079
•Niu MT, Davis DM, Ellenberg S. Recombinant hepatitis B vaccination of neonates and infants: emerging safety data from the Vac cine Adverse Event Reporting System. Pediatr Infect Dis J.
Sep 1996;15(9):771- 6. doi:10.1097/00006454- 199609000- 00007
•Niu MT, Salive  ME, Ellenberg SS. Neonatal deaths after hepatitis B vaccine: the vaccine adverse event reporting system, 1991 -1998. Arch Pediatr  Adolesc  Med . Dec 1999;153(12):1279- 82.
doi:10.1001/archpedi.153.12.1279
•Sapru A, Kulkarni PS, Bhave S, Bavdekar A, Naik SS, Pandit AN. Immunogenicity and reactogenicity of two recombinant hepatitis B vaccines in small infants: a randomiz ed, double -blind
comparative study. J Trop Pediatr. Oct 2007;53(5):303- 7. doi:10.1093/ tropej /fmm016
•Verstraeten  T, Davis RL, DeStefano F, et al. Safety of Thimerosal- Containing Vaccines: A Two -Phased Study of Computerized Health Maintenanc e Organization Databases. Pediatrics.
November 2003;112(5):1039- 1048. doi:10.1542/peds.112.5.1039
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.
Questions?

Summary: A Review of the Safety of Hepatitis B Birth Dose  Vaccination John Su Acting Director Immunization Safety Office Centers for Disease Control and Prevention September 18, 2025National Center for Emerging and Zoonotic Infectious Diseases Request to CDC from ACIP Chair Safety data for HepB administration within 24 hours of birth from CDC’s  Vaccine Safety Datalink and from FDA’s Biologics Effectiveness and Safety  System. Include (i) mild and serious adverse events; (ii) all cause morbidity and…


03 su hep b 508

Non -specific effects following hepatitis B
vaccinationNational Center for Emerging and Zoonotic Infectious Diseases
John Su
Acting DirectorImmunization Safety OfficeCenters for Disease Control and Prevention
September 18, 2025
1
Request to CDC from ACIP chair
Present the results for the HepB  vaccine from the study by Garly ML,
Jensen H, Martins CL, Balé  C, Baldé MA, Lisse IM, Aaby P . Hepatitis B
vaccination associated with higher female than male mortality in Guinea -
Bissau: an observational study. The Pediatric infectious disease journal.
2004 Dec 1;23(12):1086 -92.
2
Outline
•Review non -specific effects following vaccination
•Summarize Garly, et al. 2004 paper
•Through a rapid systematic review of non- specific effects following hepatitis
B vaccination, provide available evidence related to mortality following
hepatitis B vaccination
3
Non-specific effects following vaccination
Pittet L, Netea MG, Curtis N. Chapter 3 -  Non-specific Effects of Vaccines. In: Stanley A. Plotkin WAO, Paul A. Offit, and Kathryn M. Edwards, ed.Plotkin's Vaccines. 8 ed. Elsevier; 2023:37 -44.e7:chap 3.•In addition to protecting against their target disease, vaccines may
induce changes in the immune system that have broader effects
•Non -specific effects (NSE) are distinct from adverse events, cross -
protective, and downstream indirect effects
•Clinical manifestations of NSE
-All-cause mortality
-Unrelated infections
-Risk of allergic and autoimmune disease
•Live -attenuated and non-live vaccines may have differential NSE
4
Summary of Garly, et al. 2004 article
5
Background
•Several studies have examined the non- specific effects of
vaccines on all -cause mortality
•Few studies had examined a potential impact of hepatitis B
vaccination and mortality
•Objective of Garly, et al. 2004 paper:
-Is hepatitis B vaccine associated with sex -specific differences in
mortality?
6
Methods
•Study setting:
-Guinea -Bissau Bandim Health Project surveillance system
-Enrolled  inmeasles vaccine trial1
•Study population:
-Birth cohorts, March 1994 – February 2000
-Children born March 1996 –February 1997, eligible for hepatitis B vaccine
•Study design: prospective cohort
•Exposure:
-3 doses of hepatitis B vaccine given at 7.5, 9, and 10.5 months of age
-Human plasma- derived hepatitis B vaccine, Hepaccine  (not a U.S. licensed vaccine)2
1. Garly ML, Martins CL, Balé  C, da Costa F, Dias F, Whittle H, Aaby P. Early two -dose measles vaccination schedule in Guinea -Bissau: good protection and cov erage in infancy. Int J
Epidemiol. 1999 Apr;28(2):347 -52. doi: 10.1093/ ije/28.2.347. PMID: 10342702.
2. Heppacine  is not approved for use in the United States; HEPACCINE -B INJECTION - 27/30.1/0128; HEPACCINE -B MULTIDOSE INJECTION - 27/30.1/0129; HEPACCINE -B PAEDIATRIC
INJECTION - 27/30.1/0127; HEPACCINE -B PAEDIATRIC 2 DOSE INJECTION -  27/30.1/0422; HEPACCINE -B PAEDIATRIC MULTIDOSE INJECTION - 27/30.1/0423 7
Methods
•Three mortality comparisons:
1.Children aged 7.5 - 12 vs 1.5 - 7.5 months, all birth cohorts
2.Hepatitis B -vaccinated vs hepatitis B -unvaccinated (subset in 2-dose
measles vaccine (MV) trial)
3.Female -to-male , hepatitis B -vaccinated vs hepatitis B -unvaccinated
(among those who received MV; HBV+MV vs MV alone)
8
Results
•Comparison 1 (N = 8,906)
-Mortality  rate ratio (MRR) was 0.97 (95% CI, 0.77- 1.23) for the HBV -unvaccinated cohorts comparing
7.5- 12-month  to 1.5- 7.5 month age groups
-Among the birth cohorts when most children received HBV (7.5 months of age ),children had
increased mortality [MRR 1.62 (95% CI 1.09, 2.41)] comparing 7.5- 12-month to 1.5- 7.5 month age
groups
•Comparison 2 (N= 5,441)
-Among children enrolled in the MV trial, compared with HBV -unvaccinated children, the MRR for
children 7.5- 12 months of age from the HBV -vaccinated cohort was 1.81 (95% CI 1.19, 2.75)
•Comparison 3 (N=5,061)
-The female -to-male  MRR was 1.66 (95% CI 0.80- 3.45) in the cohort  who received both HBV and MV
through 12 months of age
-The female -to-male MRR was 2.20 (95% CI 1.07, 4.54) in cohort who received both HBV and MV and
0.96 (95% CI 0.70, 1.32) in the MV only cohort through 24 months of age
9
Conclusions
•Garly, et al. concludes, using 3 different tests of the same intervention:
-Changes in the mortality pattern after the introduction of hepatitis B vaccine in a
high mortality setting
-Higher mortality between 7.5 and 12 months of age among children who
received hepatitis B vaccine compared to those who did not, within a 2 -dose
measles vaccine trial
-The effect was found to be stronger for females than for males
-Hepatitis B vaccine may have sex -differential non -specific effects
10
Limitations and Implications
•Analyses were not planned when the trial was designed
•The study was not randomized, so an unbiased comparison of hepatitis B -
vaccinated and unvaccinated children from the same period could not
bemade
•Effects may differ when hepatitis B vaccine is given at birth and with BCG
•An increase in the female -to-male mortality ratio could also represent a
reduction in male mortality
11
Rapid systematic review of non- specific
effects of hepatitis B vaccine
12
Rapid systematic review of non- specific effects after
hepatitis B vaccination
•To inform the Garly et al. 2004 paper, we conducted a rapid systematic
review on the non -specific effects (e.g., mortality) after hepatitis B
vaccination in children
•The key question used to guide the review: What are the non-
specific effects of hepatitis B -containing vaccines administered in
childhood?
13
Rapid systematic review of data on non- specific effects
•Key question: What are the non -
specific effects of hepatitis B -
containing vaccines administered in
childhood?
•Conducted a new rapid systematic
review of published literature through August 20, 2025
•Electronic databases
searched: MEDLINE, EMBASE,
CINAHL, and Cochrane LibraryPI/ECO(ST)
ELEMENTDescription for this Review
PopulationInfants and children through 6 years of age
Intervention or
Exposure*Hepatitis B (HBV) – Recombivax HB,Engerix -B
Combination vaccines –
Pediarix, Kinrix, Quadracel, Vaxelis, Pentacel, ProQuad
Comparator (if applicable)Any or none
Outcome(s)Non- specific effects
All-cause morbidity
All-cause mortality (death)
Non- targeted infection (sepsis, respiratory tract)
Allergic and atopic disease (asthma, eczema, atopic dermatitis, food allergy)
Autoimmune and immune- mediated disease (type 1 diabetes mellitus,
inflammatory bowel disease – ulcerative colitis and Crohn’s disease,
juvenile idiopathic arthritis, systemic lupus erythematosus, Hashimoto’s
thyroiditis, alopecia)Malignancy (cancer, leukemia)
SettingAny
Time Frame Any publication years
Any duration of follow up
14
Results
15
Systematic review inclusion and exclusion criteria
Inclusion Criteria Exclusion Criteria
• Clinical trials
• Observational studies
• Surveillance reports
• Systematic reviews• Case reports
• Case series
• Narrative reviews
• Animal studies
• Infants
•Children ≤ 6 years of age•Older children ≥7 years of age
• Adults
• Hepatitis B vaccines (Hepatitis B,
H BV, HepB, Engerix -
B,Recombivax HB, Pediarix, Vaxelis)• Other vaccines
• Outcomes include any of the following: non-specific effects, all -cause morbidity, all -
cause mortality, non- targeted infection,
allergic and atopic disease, autoimmune and
immune -mediated disease, malignancy• Any other outcome
16
Results of systematic reviewIdentification Screening IncludedStudies from databases/registers (n = 2068)
Embase (n = 1105)
MEDLINE (n = 811)
Cochrane Library (n = 119)
CINAHL (n = 33)References removed (n = 0)
Duplicates identified manually (n = 0)
Key word screening for “hepatitis B,” “HBV,” “Hep B,”
“Engerix -B,” “Recombivax HB,” “ Pediarix ,” “Vaxelis ”(n
= 2068)Studies excluded (n = 1831)
Studies sought for retrieval (n = 16)Studies excluded (n = 221)
Studies assessed for eligibility (n = 16)    Studies excluded (n = 8)
Wrong study design (case report, case series, etc.) (n=3)
Wrong patient population (children>/=7, adolescents, adults) (n=1)
Wrong intervention (does not evaluate hepatitis B -containing vaccines) (n=4)
Studies included in review (n = 8)
Studies screened (n = 237)
Studies not retrieved (n = 0)
17
Summary of publications meeting search criteria
•Total of 8 studies included in review
-4 studies evaluated pentavalent, hepatitis B -
containing vaccines* and non -specific effects
-4 studies evaluated monovalent hepatitis B
vaccines and non- specific effects
•Study characteristics (N=8)
•Presenting results of studies
(N=4) evaluating monovalent hepatitis B
vaccination
*Pentavalent vaccine: Diphtheria- Tetanus -whole cell Pertussis- Hemophilus influenzae type B- Hepatitis BCharacteristic # of Studies
Study design Cohort 7
Nested case series 1
Vaccine adm inistered Pentavalent vaccine 4
M onovalent hepatitis B  vaccine4
C ountry of study High income country 2
Lo w- and mi ddl e -
income country6
Non-specific effects Mortality 4
Fem ale -to-m ale
m ortality5
Other non- specific
effects1
18
StudyStudy
TypeCountryOutcome and
WindowComparison armsNon -Specific Effects
Measure of
AssociationIntervention
Results
% (n/N or PT)Comparison
Results
% (n/N or PT)
He 2022 Cohort United StatesAll-cause mortality;
median follow -up of 8
yearsHepatitis B vaccine*
vs no hepatitis B
vaccine(390/10,785)2.6
(4,185/26,006)aHR 0.78 (95%CI: 0.
68-0.90)
Morgan
2025Cohort
(extrem
elypret
erm inf
ants)AustraliaAll-cause mortality;
within 3 months of lifeHepatitis B vaccine vs
no hepatitis B vaccine2.3 (7/306) 2.7 (14/512)aRR :
1.13 (95%CI: 0.42-
2.81)
Garly 2004 Cohort Guinea -BissauAll-cause mortality;
7.5 months –
12months of ageHepatitis B
vaccine [Hepaccine ]
+measles vaccine
vsmeasles vaccineNR/876 NR/4,565MRR
1.81 (95%CI: 1.19-
2.75)Studies evaluating mortality
Two cohort studies in high- income countries (HIC) showed no association between all -cause
mortality and hepatitis B vaccination, and one cohort study in a low -and middle -income
country (LMIC) suggested an increase in risk of all -cause mortality after hepatitis B vaccination.
PT = person -time; aHR = adjust hazard ratio; aRR = adjusted rate ratio; NR = not reported; MRR = mortality rate ratio
•*Unspecified manufacturer, thimerosal -free 19
StudyStudy
TypeCountryOutcome and
WindowComparison armsNon -Specific Effects
Measure of
AssociationIntervention
Results
% (n/N or PT)Comparison
Results
% (n/N or PT)
Garly 2004 Cohort Guinea -BissauFemale -to-
male mortality; 7.5
months – 12months
of ageHepatitis B vaccine
[Hepaccine] +
measles vaccine vs
measles vaccine12.5 (18/143.8
female person-
years)7.5 (12159.1
male person-
years)MRR 1.66 (95%CI: 0
.80- 3.45)
Garly 2004 Cohort Guinea -BissauFemale -to-
male mortality; 9 -24
monthsHepatitis B
vaccine [Hepaccine]
+ measles vaccine vs
measles vaccine6.1 (22/358
female person-
years)2.8 (11/394.3
male person-
years)MRR
2.20 (95%CI: 1.07-
4.54)
Aaby 2004Nested
case
seriesThe GambiaFemale -to-
male mortality; 18
months of ageHepatitis B as last
vaccine vs no
hepatitis B as last
vaccine7 (4/60) 0 (0/53) NRStudies evaluating female- to-male mortality
Evidence is inconsistent about sex -specific mortality after receipt of hepatitis B vaccines in
LMIC; one study suggests both no difference and an increase in the female -to-male mortality
ratio and one study suggests no difference in mortality by sex.
PT = person -time; MRR = mortality rate ratio; NR = not reported 20
StudyStudy
TypeCountryOutcome
and WindowComparison armsNon -Specific Effects
Measure of
AssociationIntervention
Results
% (n/N or PT)Comparison
Results
% (n/N or PT)
He 2022 Cohort United StatesCancer- related
mortality;
median follow -
up of 8 yearsHepatitis B
vaccine* vs no
hepatitis B vaccine0.7 (97/10,785)2.6
(881/26,006)aHR 0.76 (95%CI:
0.58 -1.00)
He 2022 Cohort United StatesCardiovascular
-related
mortality;
median follow -
up of 8 yearsHepatitis B vaccine*
vs no hepatitis B
vaccine0.4 (53/10,785)1.9
(732/26,006)aHR 0.83 (95%CI:
0.60 -1.15]Studies evaluating other mortality outcomes
One cohort study in a HIC suggests no effect of hepatitis B vaccines on
cancer -related mortality and cardiovascular -related mortality.
PT = person -time; aHR = adjusted hazard ratio
*Unspecified manufacturer, thimerosal -free 21
Conclusions
•Few studies exist to inform the non-specific effects of hepatitis B vaccination
•Two cohort studies in HIC showed no association between all -cause mortality
and hepatitis B vaccination
•One cohort study in an LMIC showed an increase in risk of all -cause mortality
after hepatitis B vaccination
•Evidence is inconsistent about sex -specific mortality after receipt of hepatitis B
vaccines
22
CDC’s interpretation on limitations and implications
•Non -specific effects (NSE) may vary in settings with different background
mortality rates and infectious diseases burden
•NSE may not be generalizable across immunization programs
-Heppacine  is not licensed for use in the United States
-In the United States , hepatitis B vaccine is given earlier  and often in combination with
other routine vaccines
•Biologic molecular and immunological mechanisms for non-specific effects are
not fully understood
-The interval between vaccination and the onset of NSE, as well as the persistence
ofeffects are uncertain
-The duration of a vaccine's NSE is complicated by a subsequent vaccination with adifferent vaccine
23
References
1.Pittet L, Netea  MG, Curtis N. Chapter 3 -  Non -specific Effects of Vaccines. In: Stanley A. Plotkin WAO, Paul A. Offit, and Kathryn M. Edwards,
ed. Plotkin's Vaccines . 8 ed. Elsevier; 2023:37- 44.e7:chap 3.
2.Aaby P, Jensen H, Walraven G. Age -specific changes in the female -male mortality ratio related to the pattern of vaccinations: An observational
study from rural Gambia. Vaccine . 29 May 2006;24(22):4701 -4708. doi:10.1016/j.vaccine.2006.03.038
3.Aamand T, Fisker AB, Correia C, Fernandes M, Clipet -Jensen C, Thysen  SM. Do Pentavalent ( DTwP -Hib-HBV) vaccines have sex -differential
nonspecific effects? An observational study. Observational Study Research Support, Non -U.S. Gov't. Hum Vaccin  Immunother . 12 15
2023;19(3):2288297. doi:10.1080/21645515.2023.2288297
4.Fisker AB, Biering -Sorensen S, Lund N, et al. Contrasting female -male mortality ratios after routine vaccinations with pentavale nt vaccine versus
measles and yellow fever vaccine. A cohort study from urban Guinea -Bissau. Research Support, Non -U.S. Gov't. Vaccine . 08 31 2016;34(38):4551 -
4557. doi:10.1016/j.vaccine.2016.07.034
5.Fisker AB, Thysen  SM. Non -live pentavalent vaccines after live measles vaccine may increase mortality. Research Support, Non- U.S. Gov't. Vaccine .
10 01 2018;36(41):6039 -6042. doi:10.1016/j.vaccine.2018.08.083
6.Garly ML, Jensen H, Martins CL, et al. Hepatitis B vaccination associated with higher female than male mortality in Guinea- Bissa u: An observational
study. Pediatr  Infect Dis J . December 2004;23(12):1086 -1092. doi:10.1097/01.inf.0000145700.77286.94
7.Hanifi SMA, Biering -Sorensen S, Jensen AKG, Aaby P, Bhuiya A. Penta is associated with an increased female -male mortality ratio:  cohort study
from Bangladesh. Research Support, Non -U.S. Gov't. Hum Vaccin  Immunother . 01 02 2021;17(1):197 -204. doi:10.1080/21645515.2020.1763084
8.He WQ, Guo GN, Li C. The impact of hepatitis B vaccination in the United States, 1999 -2018. Hepatology . 06 2022;75(6):1566 -1578.
doi:10.1002/hep.32265
9.Morgan HJ, Nold MF, Kattan GS, et al. Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a co hort study, Australia.
Vaccination contre  l'hepatite  B de prematures  et risque  de dysplasie  bronchopulmonaire : etude de cohorte  en Australie , Vacunacion contra la
hepatitis B en neonatos prematuros  y riesgo  de displasia broncopulmonar : estudio  de cohortes en Australia. Bull World Health Organ .
2025;103(3):187 -193. doi:10.2471/BLT.24.291683
24
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.
Questions?

Summary: Non -specific effects following hepatitis B  vaccinationNational Center for Emerging and Zoonotic Infectious Diseases John Su Acting DirectorImmunization Safety OfficeCenters for Disease Control and Prevention September 18, 2025 1 Request to CDC from ACIP chair Present the results for the HepB  vaccine from the study by Garly ML,  Jensen H, Martins CL, Balé  C, Baldé MA, Lisse IM, Aaby P . Hepatitis B  vaccination associated with higher female than male mortality in Guinea - Bissau: an…


01 levi covid 508

ACIP Meeting, Atlanta
September 19, 2025ACIP COVID -19 IMMUNIZATION WG:
INTRODUCTION
Professor Retsef Levi, PhD, MIT
ACIP Meeting, Atlanta
September 19, 2025Immediate Goals
1)Formulate possible recommendations regarding the recent FDA authorized
products with respect to sub- populations for discussion and vote during the ACIP
meeting on Sep 18- 19 (with supporting data/analyses):
-What are the appropriate subgroups (age, risk factors, prior infection, others)?
-Options: Recommend, not recommend, Individual -based decision
2)Formulate a list of risks and uncertainties the WG suggests should be communicated to patients and medical providers as part of inform consent (changes to the Vaccine Information Statement)
ACIP Meeting, Atlanta
September 19, 2025Medium -Term Goals
1)Expansive Terms of Reference
2)Three focus clusters assigned to WG members based on expertise
3)The goal for each cluster is to summarize ALL available knowledge for
discussion in the WG and highlight important issues and knowledge gaps
4)Formulate policy options on broad vaccination- related issues for consideration
by ACIP
ACIP Meeting, Atlanta
September 19, 2025Values & Conduct
1)Leverage all relevant published and unpublished scientific, clinical and public
health data, information and knowledge, including experiences from the field
2)Personalized risk -benefit analyses vs. ‘safe & effective’ (broad set of questions)
3)Debate with respect
4)Communicate the WG members’ diverse positions and opinions with maximum
transparency
ACIP Meeting, Atlanta
September 19, 2025Today’s WG Member Presentations
1)Professors Wafik El-Deiry (Brown University) and Charlote Kuperwasser (Tuffs
University):
Safety Uncertainties of COVID -19 Vaccines
2)Professor Bruce Carleton (University of British Columbia):Genomics of Vaccine-Induced Myocarditis
3)Professors Hennery Bernstein (Hofstra/Northwell in New York), Mitchell Miglis (Stanford)
and Stanely Perlman (University of Iowa)WG Minority Opinion
ACIP Meeting, Atlanta
September 19, 2025Other ACIP Members on WG
1.James Pagano, MD, FACEP, Emergency Medicine Physician
with More than 40 Years Clinical Experience, ACIP Committee
Member
2.Robert Malone, MD, MS, Vaccinologist, Scientist, Biochemist, Contributor to mRNA Vaccine Technology, ACIP Committee
Member
ACIP Meeting, Atlanta
September 19, 2025WG External Subject Matter Experts
1. Henry H. Bernstein, DO, MHCM, FAAP , Professor of
Pediatrics, Zucker School of Medicine at Hofstra/Northwell
2. Christine Stabell Benn, PhD, DMSc , Bandim Health
Project, OPEN, Department of Clinical Research, University of Southern Denmark
3. Bruce Carleton, Pharm.D , Professor, University of
British Columbia
4. Wafik El-Deiry , MD, PhD, FACP , Director, Legorreta
Cancer Center at Brown University
5. Joseph Fraiman, MD, Emergency Medicine Physician, Baton Rouge, LA
6. Suzanne Gazda, MD, Medical Director, Neurology institute of San Antonia (NISA)
7. Douglas H. Jones, MD, FAAAAI, FACAAI, Board certified American Board of Allergy and Immunology; CEO Global Allergy Immune Network7. Charlotte Kuperwasser, PhD, Professor,
Developmental, Molecular & Chemical Biology,
Director, Tufts Convergence Laboratory of Biomedical, Physical, and Engineering Sciences, Tufts University
8. Mitchell Miglis , MD, Clinical Associate Professor,
Department of Neurology and Neurological Sciences, Secondary in Department of Psychiatry and Behavioral Sciences, Stanford University
9. Stanley Perlman, MD, PhD, Professor, Department of
Microbiology and Immunology, University of Iowa
10. Erle Robertson, PhD., Harry P . Schenk Endowed Chair
Professor, Vice -Chair, Department of
Otorhinolaryngology, Head and Neck Surgery
11. Jordan Vaughn, MD, CEO of MedHelp Clinics
ACIP Meeting, Atlanta
September 19, 2025ACIP Ex Officio
1.Tracy Beth Hoeg, MD, PHD, Senior Advisor for Clinical
Sciences, Food and Drug Administration Ex Officio
2.Andrew Johnson, Centers for Medicare & Medicaid Services
Ex Officio

Summary: ACIP Meeting, Atlanta September 19, 2025ACIP COVID -19 IMMUNIZATION WG: INTRODUCTION Professor Retsef Levi, PhD, MIT ACIP Meeting, Atlanta September 19, 2025Immediate Goals 1)Formulate possible recommendations regarding the recent FDA authorized  products with respect to sub- populations for discussion and vote during the ACIP  meeting on Sep 18- 19 (with supporting data/analyses): -What are the appropriate subgroups (age, risk factors, prior infection, others)? -Options: Recommend, not…


02 Srinivasan covid 508

Updates to COVID -19 epidemiology
Advisory Committee on Immunization Practices
September 19, 2025
1U.S. Centers for Disease Control and Prevention

COVID -NET monitors COVID -19 hospitalizations across
parts of the U.S.
•RESP -NET includes COVID -NET, RSV -NET, FluSurv -NET
•Collaboration between state and local health
departments and CDC
•Includes data from >300 hospitals in 185 counties
across 13 states, covering about 10% of the U.S.
population
COVID -NET: https://www.cdc.gov/covid/php/covid -net/index.html . 2
Types of COVID -NET data
1.Population -based rates of COVID -19–
associated hospitalizations
-Counts every laboratory -confirmed COVID -
19–associated hospitalization among
people living in COVID -NET counties
-Includes all hospitalizations that meet the
COVID -NET case definition:
•Laboratory -confirmed SARS -CoV-2-
positive test result
•Resident of COVID -NET catchment area
-Collects some data (age, sex, race/ethnicity,
site, test/admission dates) for all cases
32.Clinical data (including outcomes,
underlying medical conditions,
treatment, discharge diagnoses)
-Obtained via detailed medical chart
reviews from anonymous, random sample
of hospitalizations (since reviewing every
case is not possible)
•Monthly random sample from each of six
age groups at each site designed to
represent the broader population
-Clinical analyses limited to hospitalizations
due to COVID -19
Purpose of COVID -NET data
1.Population -based rates of
COVID -19–associated hospitalizations
42.Clinical data (including outcomes,
underlying medical conditions,
treatment, discharge diagnoses)
•Monitor laboratory -confirmed COVID -19-
associated hospitalizations among children
and adults
•Provide decision -makers and public with
broad and timely (weekly) understanding of
general trends
‒Rates published weekly on public
dashboard since 2020
•Estimate and compare disease burden over
time
•Respond to rising rates•Categorize hospitalizations that are due to
COVID -19
•Better understand hospitalization trends
and who is most at risk
•Track severity of illness
•Examine how many people hospitalized due
to COVID -19 have underlying medical
conditions
•Provide insight into treatments used
Defining Hospitalizations in COVID -NET
5
1. Definition of COVID -NET hospitalizations for
population -based rates
How does COVID -NET define a COVID -19–associated hospitalization?
•A hospitalization (case) is counted if:
-The person lives in a defined COVID -NET surveillance catchment area AND
-Tests positive for SARS -CoV-2 (using a laboratory -based molecular, antigen
or serology test) within 14 days before or during hospitalization
6
1. Definition of COVID -NET hospitalizations for
population -based rates (cont’d)
Why use this definition?
•Designed to monitor overall trends in hospitalizations
-Simple approach works across hundreds of hospitals
-Available in near real -time
-Same definition used to monitor hospitalizations for
other pathogens (RSV, influenza) in the U.S. and
worldwide
•Developed by infectious disease experts
•Balances accuracy, speed, and broad coverage
7This approach is used
internationally* to conduct
COVID -19 hospitalization
surveillance, including in
Australia, Canada,
Denmark, France,
Germany, India, Ireland,
Italy, Netherlands,
New Zealand, South
Africa, Spain, Sweden, the
United Kingdom, and the
European Union.
*Australia: PAEDS, Denmark; SSI national registers, France: SI -VIC, Germany: SurvNet, India: NCRC, Ireland: HPSC, Italy: Sorvegl ianza Integrata COVID -19,Netherlands: NICE/RIVM, South
Africa: DATCOV, Spain: RENAVE, Sweden: FoHM national reporting, the United Kingdom: NHS COVID -19 Hospital Activity data, and the  European Union: ERVISS.
2. Definition of hospitalizations due to COVID -19 used
for clinical analyses
How does COVID -NET define hospitalizations “due to COVID -19”?
•“With” vs. “for” (due to) debate related to COVID -19 hospitalizations
•Early in the pandemic, hospitals screened every patient when they arrived
at the hospital
•This captured hospitalizations among patients who tested positive for SARS -
CoV-2 admitted for other reasons (e.g., surgery, labor and delivery)
•To address this, COVID -NET developed an algorithm to identify cases for
which COVID -19 was the likely primary reason for admission, hereafter
referred to as “hospitalizations due to COVID -19”
-Algorithm uses chief complaint and history of present illness
-Data for all current and previous surveillance periods back to March 2020 are
posted monthly on public dashboard
COVID -NET Interactive Data Dashboard: https://www.cdc.gov/covid/php/covid -net/index.html  8
Why classifying hospitalizations as “with” or “due to”
COVID -19 is not simple
•It can be difficult to identify a single cause for hospitalization
•A positive SARS -CoV-2 test can influence the decision to admit someone
with medical conditions/comorbidities
•Additionally, presence of medical conditions/comorbidities can influence
the decision to admit someone who tests positive
•SARS -CoV-2 testing, treatment, discharge diagnosis codes, and other
clinical data elements can all misclassify hospitalizations with respect to
whether or not they are due to COVID -19
-ICD-10-CM codes in the U.S. are designed for administrative and billing purposes, not
surveillance, and may overcount or undercount
‒COVID -19 code may be used just to indicate positive SARS -CoV-2 test*
9ICD-10-CM: International Classification of Disease, Tenth Revision, Clinical Modification
*ICD -10-CM Official Guidelines for Coding and Reporting FY 2025 -- UPDATED October 1, 2024 (October 1, 2024 - September 30, 2025 ): https://stacks.cdc.gov/view/cdc/158747 . Inpatient
guidance: If the diagnosis documented at the time of discharge is qualified as “probable,” “suspected,” “likely,” “questionable,” “poss ible,” “still to be ruled out,” “compatible with,”
“consistent with,” or other similar terms indicating uncertainty, code the condition as if it existed or was established.
How COVID -NET defines hospitalizations due to COVID -
19 using likely primary reason for admission
*Complaints with any attribution to specific/known etiology (i.e. appendicitis, imaging -
identified, substance abuse/overdose/withdrawal) or related to: trauma; biliary or
cirrhosis; cancer/mass/leukemia/tumor; cellulitis/abscess/localized infection; foreign body,
genitourinary, back/extremity/joint pain, surgical complication, medication reaction,
preeclampsia or gestational hypertension, ingestion/poisoning, medical device, scheduled
treatment/chemotherapy 10Is chief complaint/history of present
illness (HPI) related to:
•Obstetrics/labor and delivery
•Inpatient surgery or procedure (e.g.,
joint or heart valve replacement)
•Psychiatric admission needing acute
medical care
•Trauma (e.g., car crash, fracture), or
•Hospitalized at birth (newborn)?All laboratory -confirmed COVID -19–
associated hospitalizations Is chief complaint/ HPI reason for admission noted as:
•Fever or respiratory illness
•COVID -19–like illness, or
•Suspicion for COVID -19?
NO
Reason for admission reviewed by 2 physicians;
3rd physician resolves disagreements
YES
EXCLUDENO
Indicates SARS -CoV -2 was
incidental finding or
hospitalization unlikely
related to COVID -19*Indicates
hospitalization
likely related
to COVID -19YES
Hospitalization due to
COVID -19
87% of all recent hospitalizations among SARS -CoV-2-positive patients were
due to COVID -19 based on reason for admission
Data are posted publicly: https://www.cdc.gov/covid/php/covid -net/index.html . Likely reason for admission due to COVID -19 is defined as SARS -CoV-2-positive test ≤14 days before/during
hospitalization AND chief complaint or history of present illness in medical record indicates fever, respiratory illness, COV ID-19-like illness, or suspicion for COVID -19-like illness. 1189
69839187
0102030405060708090100
0–17 years 18–49 years 50–64 years ≥65 years OverallWeighted percent of COVID -NET hospitalizations
Age groupPercent of COVID -19-associated hospitalizations due to COVID -19 based on reason
for admission, by age group and surveillance season —
COVID -NET, October 2022 –May 2025
2022 –2023 2023 –2024 2024 –2025•Percent of COVID -19–associated
hospitalizations due to COVID -19
have increased over time
•No longer widespread screening
of asymptomatic patients
•Percent of COVID -NET
hospitalizations due to COVID -19
increases with age among adults
•Adults ages ≥65 years account for
70% of COVID -19–associated
hospitalizations, of which 91% are
considered due to COVID -19 based
on reason for admission.70% of COVID -19–
associated hospitalizations
How COVID -NET goes beyond billing codes
•Not all partner hospitals are able to provide final ICD -10-CM codes
-Coding may be delayed or limited
-Coding may be stored only in inaccessible billing systems
•COVID -NET surveillance officers also review the discharge summary for each patient
-Capture conditions that were not present at admission but developed during the hospital stay
-Gives fuller picture of patient’s hospitalization and reduces some of the bias that comes from
relying only on billing codes
12
COVID -NET hospitalizations classified as due to COVID -19 or
with COVID -19 using two different approaches
1366,125 COVID -19 hospitalizations among patients of
all ages during October 2023 –September 2024
7,279 (11%) random sample of
hospitalizations with chart review
81% 52%
88%
*Respiratory -related defined as acute respiratory distress syndrome (ARDS), acute respiratory failure, asthma exacerbation, bron chiolitis, bronchitis, chronic obstructive pulmonary disorder (COPD) exacerbation, or
pneumonia as indicated by the abstracted condition from discharge summary or the presence of an ICD -10-CM discharge diagnosis co de.COVID -19
ICD-10-CM
code
COVID -19 ICD -10-CM
code or sepsis or
respiratory -related*
discharge diagnosisSepsis or respiratory -
related* discharge
diagnosis
Neither COVID -19 ICD -
10-CM code nor sepsis
or respiratory -related*
discharge diagnosis12%ICD -10 codes and discharge diagnoses approach
66,125 COVID -19 hospitalizations among patients of
all ages during October 2023 –September 2024
7,279 (11%) random sample of
hospitalizations with chart review
85%
COVID -19 likely
reason for admission
Non -COVID -19 reason
for admission15%COVID -NET reason for admission approach
84%
COVID -19
ICD-10-CM
code
57%
Pulmonary
or sepsis
discharge
diagnosis91%
Either
COVID -19
ICD-10-CM
code OR
pulmonary
or sepsis
discharge
diagnosis64%
COVID -19
ICD-10-CM
code
Key Takeaways
•Two approaches for defining hospitalizations due to COVID -19
-COVID -19 identified as reason for admission
-COVID -19-related discharge diagnoses
•Similar proportions of patients classified using both methods:
-88% had COVID -19 ICD -10-CM code or sepsis or respiratory diagnosis
-85% identified by COVID -NET as COVID -19 being likely primary reason for admission
•91% of hospitalizations using COVID -NET’s reason for admission approach had a COVID -19 ICD -10-CM
code or sepsis or respiratory diagnosis
•COVID -NET’s reason for admission approach is more conservative than examining
discharge diagnoses
•COVID -NET’s methods for identifying hospitalizations due to COVID -19 balances
timeliness, accuracy, and representativeness
14
Population -based rates of COVID -19–
associated hospitalizations
15
Rates of COVID -19–associated hospitalization are
highest among the youngest and oldest age groups
A COVID -19–associated hospitalization is defined as laboratory -confirmed SARS -CoV-2 in a person who (a) lives in a defined COVID -NET surveillance catchment area AND (b) tests positive
for SARS -CoV-2 (using a laboratory -based molecular, antigen or serology test) within 14 days before or during hospitalization. 16223
117
298 82774195653
0100200300400500600700
<6 months 6–11 months 1–4 years 5–11 years 12–17 years 18–49 years 50–64 years 65–74 years ≥75 yearsHospitalizations per 100,000 population
Age groupPopulation -based COVID -19–associated hospitalization rates (per 100,000 population), by age group —
COVID -NET, October 2024 –September 2025
Rates are presented per 100,000 population and indicate the cumulative
12-month age group -based risk of COVID -19–associated hospitalization.
Among adults hospitalized due to COVID -19, 15% were
admitted to the intensive care unit (ICU)
1725
1917
14
145
051015202530
0–17 years 18–49 years 50–64 years ≥65 yearsWeighted percent of hospitalizations
Age groupWeighted percent (with 95% confidence intervals) of patients hospitalized due to COVID -19 with interventions
and outcomes, by age group — COVID -NET, June 2024 –May 2025
ICU admission In-hospital death<1
The figure displays the proportion of adults hospitalized due to COVID -19 based on reason for admission with interventions and o utcomes, by age group — COVID -NET, June 2024 –May
2025. Error bars denote 95% confidence intervals (95% CI).  Data are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Deaths do not include other COVID -
19-related deaths that might occur after a patient is discharged to hospice or deaths that occur soon after hospital discharge t hat could be attributable to COVID -19-related illness.During this period, 84% of all adults hospitalized due to COVID -19 who died in -hospital were ages ≥50 years.
Burden of COVID -19-Associated
Hospitalizations among Infants
18
Rates of respiratory virus -associated hospitalizations vary
by age group and pathogen.
1902004006008001000120014001600
<1 1–4 5–11 12–17 18–49 50–64 65–74 ≥75Hospitalizations per 100,000 population
Age group, in yearsCumulative rates of COVID -19–, influenza -, and respiratory syncytial virus
(RSV) -associated hospitalizations — RESP -NET, October 2024 –September 2025
COVID-19 Influenza RSV
Rates for all three pathogens (COVID -19, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. Data source : https://www.cdc.gov/resp -net/dashboard/
Note that rates are not adjusted for testing or limited to admissions where the respiratory infection is the reason for admis sion.  Influenza surveillance was conducted October 2024 –April
2025.
Cumulative COVID -19-associated hospitalization rates are highest
among adults aged ≥75 years, followed by infants aged <6 months
and adults ages 65 –74 years.
Weekly rates of COVID -19–associated hospitalizations per 100,000 population by age group —COVID -NET, October 2024 –September 2025
Note that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 20050100150200250
Oct 2024 Nov 2024 Dec 2024 Jan 2025 Feb 2025 Mar 2025 Apr 2025 May 2025 Jun 2025 Jul 2025 Aug 2025 Sep 2025Hospitalizations per 100,000 population
Surveillance week end date
<6 months 6–11 months 1–4 years 5–11 years
12–17 years 18–49 years 50–64 years 65–74 years50–64 years:
1011–4 years:  29
18–49 years: 27
12–17 years: 8
5–11 years: 8<6 months: 223
65–74 years: 195
6–11 months: 117
50–64 years:  740200400600800Hospitalizations per
100,000 population≥75 years: 653
Relative risks of hospitalization due to
COVID -19 among adults by chronic
condition
21
Background
•Update to peer -reviewed manuscript by Ko, et al. published in Clinical
Infectious Diseases  in 2021*
* Ko J, Danielson ML, Town M, et al. Risk Factors for COVID -19-Associated Hospitalization: COVID -NET and BRFSS. https://doi.org/10.1093/cid/ciaa1419 . 22

Data Sources
•COVID -NET (number of hospitalizations due to COVID -19)
-October 2022 –September 2023
-98 counties across 13 states
•Behavioral Risk Factor Surveillance System (BRFSS) (chronic conditions)
-Largest continuously conducted health survey system in the world (hundreds of
thousands of interviews among community -dwelling U.S. adults each year)
-2022 survey
•National Center for Health Statistics (population data)
-2020 U.S. Census data
23
Overview of the Analysis
•Obtain weighted counts of persons hospitalized due to COVID -19 with and
without underlying conditions (COVID -NET)
-Limited to hospitalizations with COVID -19 as likely primary reason for admission
-Limited to community -dwelling adults to match BRFSS parameters
•Calculate weighted counts of community -dwelling adults with and
without chronic diseases of interest in participating states (BRFSS)
•Generate proportion of state population residing in the COVID -NET county
catchment area (Census)
•Calculate adjusted rate ratios of hospitalization rates with vs. without
chronic conditions
24
Chronic conditions examined
•Coronary artery disease
•History of stroke
•Diabetes mellitus
•Chronic kidney disease
•Chronic obstructive pulmonary disease (COPD)
•Asthma
•Obesity (body mass index [BMI] 30 –<40 kg/m²)
•Severe obesity (BMI ≥40 kg/m²)
•Current smoker
25
The prevalence of most chronic conditions among adults
hospitalized due to COVID -19 was generally higher than the
prevalence observed in the general population.
Error bars denote 95% uncertainty intervals (95% CI). Obesity is defined as BMI 30 –<40 kg/m². Severe obesity is BMI ≥40 kg/m². 26
Weighted prevalence (with 95% uncertainty intervals) of chronic medical conditions among adults
hospitalized due to COVID -19 compared to community -dwelling adults in COVID -NET states, 2022 –2023Weighted prevalence (%)
Among adults, most chronic conditions examined
increased the risk of being hospitalized due to COVID -19
COPD: chronic obstructive pulmonary disease. Obesity is defined as BMI 30 –39 kg/m². Severe obesity is BMI ≥40 kg/m². Note that v ertical axis is presented in logarithmic scale. 27Rate ratio (with 95% uncertainty intervals) comparing rates of COVID -19 hospitalization among
community -dwelling adults with a chronic medical condition to those without, by age group —
COVID -NET states, October 2022 –September 2023
•Risk conferred by
several conditions
appear to decline
with age (CAD,
diabetes, obesity).
This might be a
consequence of:
•Inability to
adjust for
comorbidities in
the models
•Low population
prevalence of
some conditions
in some age
groups
Risk for hospitalization due to COVID -19 increases
with the number of chronic conditions and age.
§ Model includes number of conditions, age group, sex, and race or ethnicity group.
¶ Number of conditions is a sum of chronic conditions (asthma, COPD, chronic kidney disease, coronary artery disease, diabete s, history of stroke, severe obesity, and current smoking).
Note that vertical axis is presented in logarithmic scale. 28•Multiple chronic medical
conditions and older age
were the strongest risk
factors for COVID -19
hospitalization among
adults.
•Hospitalization rates were
18.5 -times as high among
adults ages ≥75 years
compared to 18 –49 years.
•The greatest risk factor
examined in this analysis
Strengths and Limitations
•Data are gathered from robust COVID -19 hospitalization public health
surveillance system
•Ability to compare underlying conditions using state -level prevalence
•Capability to examine and compare specific underlying conditions,
prevalence of multiple conditions and age group as risk factors
•Limitations
-Results are preliminary and under review
-Analysis is limited to community -dwelling adults
-Adjustments for some comorbidities could not be made due to sparse data,
especially in younger groups.
-Unable to look at differences in rate ratios across outcomes (e.g., ICU admission)
or race and ethnicity categories due to sparse data in some categories.
29

Summary: Updates to COVID -19 epidemiology Advisory Committee on Immunization Practices September 19, 2025 1U.S. Centers for Disease Control and Prevention  COVID -NET monitors COVID -19 hospitalizations across  parts of the U.S. •RESP -NET includes COVID -NET, RSV -NET, FluSurv -NET •Collaboration between state and local health  departments and CDC •Includes data from >300 hospitals in 185 counties  across 13 states, covering about 10% of the U.S.  population COVID -NET:…


03 srinivasan covid 508

COVID-19 Vaccination Implementation National Center for Immunization and Respiratory Di seases
September 19, 2025 Immunization Services Division Centers for Disease Control and Prevention
•National Immunization Survey (NIS):
-Random-digit-dial cellular telephone survey of adul ts age ≥18 years in the U.S. (all
50 states, 5 local jurisdictions, and territories);  all responses are self reported.
-Sample size: ~15,000 adult respondents weekly, ~60, 000 adult respondents monthly
-Data are weighted to represent the non-institutiona lized U.S. population Data sources used to estimate U.S. immunization coverage
COVID-19 Vaccination Coverage
National Immunization Survey-Fall Respiratory Virus Module
0.0 20.0 40.0 60.0 80.0
9/7/2024
9/14/2024 9/21/2024 9/28/2024 10/5/2024
10/12/2024 10/19/2024 10/26/2024
11/2/2024 11/9/2024
11/16/2024 11/23/2024 11/30/2024
12/7/2024
12/14/2024 12/21/2024 12/28/2024
1/4/2025
1/11/2025 1/18/2025 1/25/2025
2/1/2025 2/8/2025
2/15/2025 2/22/2025
3/1/2025 3/8/2025
3/15/2025 3/22/2025 3/29/2025
4/5/2025
4/12/2025 4/19/2025 4/26/2025
Vaccination coverage (%)
Week ending date ≥65 years
50-64 years
18-49 years COVID-19 Vaccination Coverage (≥1 Dose) Among Adults 1 8-49 Years, 50-64
Years, and 65 Years and Older, 2024-2025
National Immunization Survey National Immunization Survey National Immunization Survey National Immunization Survey- - --Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module
44.1 24.6
14.1
025 50 75 100
Sep 7
Sep 14 Sep 21 Sep 28
Oct 5
Oct 12 Oct 19 Oct 26
Nov 2 Nov 9
Nov 16 Nov 23 Nov 30
Dec 7
Dec 14 Dec 21 Dec 28
Jan 4
Jan 11 Jan 18 Jan 25
Feb 1 Feb 8
Feb 15 Feb 22
Mar 1 Mar 8
Mar 15 Mar 22 Mar 29
Apr 5
Apr 12 Apr 19 Apr 26
Sep 7
Sep 14 Sep 21 Sep 28
Oct 5
Oct 12 Oct 19 Oct 26
Nov 2 Nov 9
Nov 16 Nov 23 Nov 30
Dec 7
Dec 14 Dec 21 Dec 28
Jan 4
Jan 11 Jan 18 Jan 25
Feb 1 Feb 8
Feb 15 Feb 22
Mar 1 Mar 8
Mar 15 Mar 22 Mar 29
Apr 5
Apr 12 Apr 19 Apr 26
Sep 7
Sep 14 Sep 21 Sep 28
Oct 5
Oct 12 Oct 19 Oct 26
Nov 2 Nov 9
Nov 16 Nov 23 Nov 30
Dec 7
Dec 14 Dec 21 Dec 28
Jan 4
Jan 11 Jan 18 Jan 25
Feb 1 Feb 8
Feb 15 Feb 22
Mar 1 Mar 8
Mar 15 Mar 22 Mar 29
Apr 5
Apr 12 Apr 19 Apr 26
Sep 7
Sep 14 Sep 21 Sep 28
Oct 5
Oct 12 Oct 19 Oct 26
Nov 2 Nov 9
Nov 16 Nov 23 Nov 30
Dec 7
Dec 14 Dec 21 Dec 28
Jan 4
Jan 11 Jan 18 Jan 25
Feb 1 Feb 8
Feb 15 Feb 22
Mar 1 Mar 8
Mar 15 Mar 22 Mar 29
Apr 5
Apr 12Apr 19Apr 26
18-49 years 50-64 years 65-74 years ≥75 years Vaccination coverage (%)
2024-25 season week ending date Vaccination coverage (2024-25) Vaccination coverage (2023-24) COVID-19 Vaccination Coverage (≥1 Dose) Among Adults  ≥18 Years, 65-
74 Years, and ≥75 Years, 2023-24 and 2024-25
National Immunization Survey-Fall Respiratory Virus  Module
24.6 24.1 42.7 37.9 46.5
38.3
14.1 14.1
025 50 75 100 Vaccination coverage (%)
Week ending date Overall (6 months-17 years) 6 months-4 years 5-11 years 12-17 years COVID-19 Vaccination Coverage* Among Children 6 Mont hs–17 Years of
Age, October 2024–April 2025, NIS-Flu
* Up-to-date with the updated 2024–25 COVID-19 vacc ine is defined as receipt of at least one vaccinati on since August 22, 2024, for children ≥5 years; fo r children <5 years, up-to-
date status was defined based on the current recomm endations that also take into account number of dose s and brand of vaccine. Up-to-date status was deter mined by survey
questions on month and year of most recent COVID-19  vaccine, and for children <5 years, total number o f COVID-19 vaccinations received and brand of most recent COVID-19
vaccine. /uni2009
2.4 16.6 10.5 0.8 1.4 9.9 8.1
0.0 10.0 20.0 30.0 40.0 50.0 60.0 18-49 (n=85) 50-64 (n=98) 18-64 (n=183) 65+ (n=172) Male (n=95) Female (n=257) Overall 18+ immunocompromised (n=355)
Weighted % (95% CI) COVID-19 Vaccination Coverage (≥2 Doses) Among Adults 18 Years and Older
Who Are Immunocompromised Who Received First Dose in August/September
2024, as of End of March 2025
National Immunization Survey National Immunization Survey National Immunization Survey National Immunization Survey- - --Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module
*Immunocompromised a dults were recommended to receive a second dose of 2 024-2025 COVID-19 vaccine
six months after their first dose .
•COVID-19 vaccination coverage for older adults impro ved in 2024-2025
compared to the previous season, but vaccination cover age for adults 18-
64 years was similar between the 2023-2024 and 2024-20 25 seasons.
•Approximately 13% of children between 6 months and 1 7 years of age
were up to date with COVID vaccination at the end o f April 2025. Summary
Place of COVID-19 Vaccination Among Adults 18 Years an d Older, 2024-2025
National Immunization Survey National Immunization Survey National Immunization Survey National Immunization Survey- - --Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module
*Among persons who reported receiving a 2024-2025 CO VID-19 vaccination since August 22, 2024 (n=9,359).  Data collected April 1-27, 2025. 67.3
12.5 8.5 5.9 1.7 1.5 1.3 0.7 0.6 0.2
020 40 60 80 100 Weighted % (95% CI) Reported place of 2024-2025 COVID-19 vaccination, a dults age ≥18 years*, United States
COVID-19 Vaccination Coverage among Health Care Personnel
National Healthcare Safety Network
•CDC’s National Healthcare Safety Network (NHSN) is the most widely used
healthcare associated infection tracking system and  provides important
quality measures like healthcare personnel (HCP) va ccination status
•CMS-certified healthcare facilities are required to  report monthly COVID-
19 vaccination data and annual influenza vaccinatio n data for HCP
•Across all healthcare facility types, the largest g roups of submitters are
Acute Care Hospitals and Nursing Homes Estimating vaccination coverage through NHSN
COVID-19 and influenza vaccine coverage among healthcare personnel (HCP) 2022-2025*
17 15
10 23
11
881 81
78
47 45
42
010 20 30 40 50 60 70 80 90
2 0 2 2 - 2 0 2 3 2 0 2 3 - 2 0 2 4 2 0 2 4 - 2 0 2 5 Vaccination Coverage (%)
COVID-19 vaccine coverage: Acute care hospital HCP COVID-19 vaccine coverage: Long term care HCP
Influenza vaccine coverage: Acute care hospital HCP Influenza vaccine coverage: Long term care HCP
References: 1. Influenza and Up-to-Date COVID-19 Vaccination Co verage Among Health Care Personnel — National Healthc are Safety Network, United States, 2022–23 Influenz a Season | MMWR
2. Influenza and COVID-19 Vaccination Coverage Among  Health Care Personnel — National Healthcare Safety Network, United States, 2023–24 Respiratory Virus S eason | MMWR
*2024-2025 Data were collected from acute care hosp itals and nursing homes on HCP influenza and up-to-d ate COVID-19 vaccination coverage for the week ending  March 30, 2025. NHSN defined up-to-date COVID-19 vac cination during that
time as the receipt of ≥1 dose of a 2024–2025 COVID -19 vaccination.
For more information, contact CDC/ATSDR 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov           www.a tsdr.cdc.gov
The findings and conclusions in this report are tho se of the authors and do not necessarily represent the official position
of the Centers for Disease Control and Prevention a nd the Agency for Toxic Substances and Disease Regi stry.
Thank you

Summary: COVID-19 Vaccination Implementation National Center for Immunization and Respiratory Di seases  September 19, 2025 Immunization Services Division Centers for Disease Control and Prevention  •National Immunization Survey (NIS):  -Random-digit-dial cellular telephone survey of adul ts age ≥18 years in the U.S. (all  50 states, 5 local jurisdictions, and territories);  all responses are self reported.  -Sample size: ~15,000 adult respondents weekly, ~60, 000 adult respondents monthly  -Data are…