04 Meyer COVID 508

CDC ACIP — Vaccine Advisory Committee

Acip

Slides

41

Document text

Update on CDC’s COVID-19 Vaccine Safety Monitoring 
Sarah Meyer, MD MPH 
Director, CDC’s Immunization Safety Office 
June 25, 2025 
1 
 
          
   
         
   
       
            
   
        Key Points 
• CDC and interagency partners launched an extensive vaccine safety monitoring 
program for COVID-19 vaccines 
• Many potential safety outcomes were rigorously assessed through complementary passive and active systems 
• Myocarditis is causally associated with mRNA COVID-19 vaccines 
-Adverse events common to all vaccines were also observed (e.g., local and 
systemic reactions, allergic reactions) 
• CDC continues to monitor the safety of COVID-19 vaccines 
2 
   
  
 
 
Interagency collaboration to 
monitor post-licensure safety 
CDC 
monitoring 
starts 
3 
       
   
 
       
        CDC’s Immunization Safety Office Monitors Vaccine Safety 
Through Strong, Complementary Systems 
VAERS VSD CISA Project V-safe 
1990 1990 2001 2020 
Systems work together to rapidly detect and assess potential 
safety concerns to help inform public health actions 
4 
     
    
       
     
      
      
            
 
        
          
VAERS 
Vaccine Adverse Event Reporting System (VAERS) 
The Nation’s Early Warning System for Vaccine Safety 
• Co-managed by CDC and FDA 
• Nationwide spontaneous reporting system that can rapidly 
detect safety signals, including rare events 
• Mandated reporting by healthcare providers and 
manufacturers, and encouraged from anyone (e.g., patients) 
• A report to VAERS does not mean that a vaccine caused an adverse event 
• Used for signal detection and hypothesis generation, not 
typically for assessing causality 
5 
      
   
       
  
        
   
     
       
      Vaccine Safety Datalink (VSD) 
Collaborative Model for High-Quality Vaccine Safety Data 
VSD • 13 integrated healthcare organizations, covering >15.5 
million people per year 
• Acti
ve monitoring using electronic medical records (EMR) 
and chart reviews 
• Rapid monitoring for pre-specified events as well as 
monitoring for unexpected events 
• Can detect and assess safety signals 
• Develops innovative methods for monitoring safety 
6 
       
     
 
    
        
       
          Clinical Immunization Safety Assessment (CISA) Project 
Network to Guide Vaccine Safety from the Individual to Population Level 
CISA Project • 8 medical research centers with vaccine safety experts 
• Pro
vides expert clinical consultation on complex 
immunization issues 
• Conducts clinical research on vaccine safety 
• Helps to inform CDC public health guidance on clinical 
immunization safety issues 
7 
     
   
         
       
        
     
        
     
      
V-safe: After-Vaccination Health Checker 
CDC’s Tool for Direct-to-Consumer Vaccine Safety Monitoring 
V-safe • Web-based, self-reported active monitoring system 
established during COVID-19 pandemic 
• Can ser
ve as earliest source of information for new 
vaccines and in populations excluded from clinical trials 
-Used to recruit women for COVID-19 Vaccine Pregnancy 
Registry 
• Important tool for emergency preparedness and response 
• Integrated with VAERS to help streamline reporting of 
ser
ious adverse events 
8 
 
  
  
   
   
   
   
   
   
   
  
    
        
  
   
   CDC’s Comprehensive Approach to Studying COVID-19 Vaccine Safety 
Surveillance Epidemiologic studies Clinical Research Pregnancy Registry 
Ana
lyze spontaneously Assess specific safety Safety studies to guide Longitudinal assessment of 
reported events questions clinical practice maternal and infant outcomes 
Rapid cycle analyses Dat a mining Pati ent surveys 
Qui
ckly detect potential Ass
ess >60,000 outcomes Ass
ess symptoms and 
con
cerns for investigation for 
unexpected events hea
lth impacts 
9 
         
    
  
 
 
   
   
  
   
    
  
                   CDC Summary of COVID-19 Vaccine Safety Data Based on 
Comprehensive Body of Evidence Collected 
December 2020 – June 2025 
17 28 29 114 ~9.6M 
VaST work 
group reports Advisory 
meeting 
presentations 
(ACIP, VRBPAC) Morbidity and 
Mortality Weekly 
Report (MMWR) 
publications Published 
manuscripts Participants 
enrolled in V-safe 
Vaccine doses distributed in U.S. ~1B
ACIP: Advisory Committee on Immunization Practices; VRBPAC: Vaccines and Related Biological Products Advisory Committee; VaST: Vaccine Safety Technical Work Group 10 
       
      
 
 mRNA 
Pfizer-BioNTech 
Moderna Three Types of COVID-19 Vaccine Received FDA 
Authorization or Approval in the United States 
Protein-based 
Novavax 
Viral Vector 
Janssen 
11 
   
                      
           
        
   
      
     
    
  
     -Janssen Use Limited After Detection of Safety Concerns in 
April 2021, and No Longer Authorized in U.S. as of June 2023 
Protein-based 
Novavax 
mRNA 
Pfizer-BioNTech 
Moderna 
EUA: Emergency Use Authorization 
Oliver S, et al. Development of COVID-19 vaccine policy — United States, 2020–2023 - ScienceDirect 
Viral Vector 
Janssen 
• By April 2021, VAERS detects 6 reports of 
thrombosis w/ thrombocytopenia 
syndrome (TTS); FDA and CDC issue a 10 
day pause in use before resuming 
• In December 2021, ACIP issues preferential 
recommendation for mRNA vaccines 
• In June 2023, FDA revokes EUA 
12 
          
           
    
   
   
    
  
   
            Janssen Use Limited After Detection of Safety Concerns in 
April 2021, and No Longer Authorized in U.S. as of June 2023 
Protein-based 
Novavax 
mRNA 
Pfizer-BioNTech 
Moderna 
EUA: Emergency Use Authorization 
Oliver S, et al. Dev
elopment of COVID-19 vaccine policy — United States, 2020–2023 - ScienceDirect 
Viral Vector 
Janssen 
Highlights an example of 
federal safety systems 
working to rapidly 
identify and mitigate a 
vaccine safety issue 
13 
      
 
    
    
 
    mRNA
Pfizer-BioNTech
Moderna -Limited Post-Authorization Safety Data Available for Novavax 
Protein-based 
Novavax 
Limited post authorization safety data 
available: 
• Authorized later than other products (July 2022) 
• Limited uptake in the U.S. 
mRNA 
Pfizer-BioNTech 
Moderna 
Viral Vector 
Janssen 
14 
       
 
 mRNA 
Pfizer-BioNTech 
Moderna Focus on mRNA COVID-19 Vaccines For This Presentation 
Protein-based 
Novavax 
Viral Vector 
Janssen 
15 
    
   Monitoring Safety of COVID-19 Vaccines 
What we have learned 
16 
16 
           
         CDC Has Evaluated At Least 65 Specific Outcomes to Assess COVID-19 
Vaccine Safety Using a Variety of Systems and Epidemiologic Methods 
Acute myocardial infarction • ICU admission • Acute disseminated encephalomyelitis • Thrombotic 
thrombocytopenic Purpura • Encephalopathy • Gestational diabetes • Trigeminal neuralgia and 
related disorders • Meningitis • Deep vein thrombosis • Anaphylaxis • Thrombocytopenia • 
Postmenopausal bleeding • Myocarditis • Cataplexy • Myelitis • Chronic inflammatory demyelinating 
polyneuropathy • Non-COVID mortality • Pulmonary embolism • Stillbirth • Major birth defects • 
Encephalitis •Local reactions •Vaccine-Associated Enhanced Disease after COVID-19 Vaccines 
• Hemorrhagic stroke • Administration errors • Acute respiratory distress syndrome • Narcolepsy • 
Perinatal death •Bell's Palsy •Thrombosis with thrombocytopenia syndrome •Multiple sclerosis 
• Systemic reaction
s • Spontaneous abortion • Ataxia • Hospitalization • Acute disseminated 
encephalomyelitis • Menstrual irregularities • Immune thrombocytopenic purpura • All-cause 
mortality • Pericarditis •Early childhood infections in infants of vaccinated mothers •Ischemic stroke 
• Shoulder injuries • Multisystem Inflammatory Syndrome in Children • Multisystem Inflammatory 
Syndrome in Adults • Tinnitus • Disseminated intravascular coagulation • Acute respiratory distress 
syndrome • Venous thromboembolism • Arthritis • Seizure • Kawasaki Disease • Arthralgia • 
Menstrual irregularities •NICU admission •Chronic inflammatory demyelinating polyneuropathy 
•Small-for-gestational age •Post-COVID conditions •Trigeminal neuralgia and related disorders 
17 
    
    
         
          
         
      
      
       
        
        
  
         
    
Weekly, Sequential Monitoring of 
Pre-Specified Outcomes in the VSD 
• Rapid cycle analyses (RCAs) conducted weekly since December 2020 
of up to 23 pre-specified outcomes among over 12 million people 
-Outcomes selected based on clinical trial data, known safety 
findings with other vaccines, or biological plausibility 
• Seq
uential statistical testing using automated ICD-10-CM codes 
-Compare incidence in vaccinated people during post-vaccination 
risk interval vs. vaccinated people in a comparison window 
• If p
otential “statistical signal” detected, additional analyses and/or 
chart reviews conducted 
-System designed to be sensitive; not all detected signals 
represent a true safety concern 
18 
        
      
                  
  
 
   
  
 
   
   
  
  
     Evaluation of Statistical Signals Detected for mRNA COVID-19 
Vaccines through VSD’s Rapid Cycle Analyses – 2020-2025 
8 statistical signals detected 
Acute myocardial infarction 
 Seizure 
Age 18+ years 18-64 years 
Immune Thrombocytopenic Purpura 
Age 65+ years 
Venous thromboembolism 
Age 12+ years Guillain-Barré syndrome 
Age 65+ years 
Bell’s Palsy 
Age 12+ years 
Ischemic stroke 
Age 50+ years 
Myocarditis 
Age 12+ years 
COVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic – ScienceDirect and CDC unpublished data 19 
        
      
                  
  
 
   
  
 
   
   
  
  
      
 
 
  
  
 
  Evaluation of Statistical Signals Detected for mRNA COVID-19 
Vaccines through VSD’s Rapid Cycle Analyses – 2020-2025 
Acute myocardial infarction 
Age 65+ years 
Venous thromboembolism 
Age 12+ years 
Bell’s Palsy 
Age 12+ years 
Ischemic stroke 
Age 50+ years 
Guillain-Barré syndrome 
Age 65+ years 
Seizure 
18-64 years 
Immune Thrombocytopenic Purpura 
Age 65+ years 
Myocarditis 
Age 12+ years 8 statistical signals detected Further investigations 
Chart reviews 
Trend analysis 
Additional studies 
(e.g., self-controlled 
case series) 
Query other 
systems 
COVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic – ScienceDirect and CDC unpublished data 20 
        
      
                  
  
 
   
  
 
   
   
  
  
      
 
 
  
  
 
      
   
      
       Evaluation of Statistical Signals Detected for mRNA COVID-19 
Vaccines through VSD’s Rapid Cycle Analyses – 2020-2025 
Acute myocardial infarction 
Age 65+ years 
Venous thromboembolism 
Age 12+ years 
Bell’s Palsy 
Age 12+ years 
Ischemic stroke 
Age 50+ years 
Guillain-Barré syndrome 
Age 65+ years 
Seizure 
18-64 years 
Immune Thrombocytopenic Purpura 
Age 65+ years 
Myocarditis 
Age 12+ years 8 statistical signals detected Further investigations 
system 
Chart reviews 
Trend analysis 
Additional studies 
(e.g., self-controlled 
case series) 
Query other 
COVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic – ScienceDirect and CDC unpublished data 
Increased risk for myocarditis 
following mRNA COVID-19 vaccines 
No clear or consistent evidence of 
a safety concern for the others 
Safety assessment 
21 
      
        
              
  
    
               
        
  
       
    38
6
22Myocarditis Following mRNA COVID-19 Vaccination Among 
People Ages 12–39 Years in the Vaccine Safety Datalink 
Incidence of myocarditis within 7 days of vaccination per million mRNA vaccine doses administered 
* 
6 38 
25 
2 5 
2 
Dose 1 
Original monovalent Dose 2 
Original monovalent Booster 
Original monovalent Bivalent 
2020-2021 2021-2022 2022-2023 2023-2024 2024-2025 * 
Background 
<2 per million higher in males 
• Myocarditis rare in children aged <12 years 
and adults aged ≥50 years 
* • Rates peak at age 16-17 years and are 
rate 
*St
atistically significant increased rate ratio in vaccinated concurrent comparator analysis. Source: CDC Immunization Safety Office 22 
        
       
                  
                   
                     Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination in 
FDA’s Biologics Effectiveness and Safety System (BEST), 2023—2024 Season 
Incidence (cases per million doses) during days 1—7 following vaccine administration 
FDA issued Safety Labeling Change (SLC) notification letters to the manufacturers 
on April 17, 2025, and initiated the SLC process to include new safety information on myocarditis and pericarditis for 
Comirnaty and Spikevax. Under the labeling negotiations, FDA has notified sponsors of the above data 
2025 Safety and Availability Communications | FDA ; Information courtesy of FDA 23 
      
     
              
             
       
              
 
           
            
            
       
                             
        Follow-up CDC Studies Demonstrate Most Adolescents 
and Young Adults Have Recovered From Myocarditis 
• Surveys of individuals aged 12-29 years with myocarditis after mRNA COVID-19 vaccine, and their 
healthcare providers, for whom a VAERS report was filed during January 12-November 5, 2021 
• Based on cardiologist or other healthcare provider assessment: 
83% >90% 
Fully or probably fully recovered by at Overall, fully or probably fully recovered by 
leas
t 90 days after myocarditis onset at least a 1 year after myocarditis onset 
• Among patients with abnormal cardiac MRI at 1-year evaluation, most common abnormality was late ga
dolinium enhancement 
-clinical significance unclear; majority considered recovered and cleared for all physical activity 
• No k
nown deaths or cardiac transplants 
Outcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study - The Lancet Child & Adolescent 
Health ; Outcomes at ≥1 year based on unpublished data 24 
          
             
        
             
    
            
             
    
         
          
  
                                         
                                     
                                      
                              
                     COVID-19 Vaccine Safety in Children Ages 6 Months to 11 Years 
• Risk of myocarditis following COVID-19 vaccines in children aged <12 years is low, 
par
ticularly for those aged 6 months to 5 years 
-Active, sequential analyses in the Vaccine Safety Datalink have demonstrated no statistical signals 
for 
myocarditis in children 
-No confirmed myocarditis cases in children aged <5 years in VAERS or VSD 
• Rapid cycle analyses in the VSD demonstrate no increased risks for 22 other pre -
specified outcomes following COVID-19 vaccination 
• Evaluations to assess multisystem inflammatory syndrome in children (MIS-C) following COVID-19 vaccination demonstrated that most patients had evidence of preceding SARS-CoV-2 infection 
Safety of COVID-19 Vaccination in United States Children Ages 5 to 11 Years | Pediatrics | American Academy of Pediatrics ; Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months–5 Years — United States, June 17, 2022–May 7, 2023 | 
MMWR ; COVID-19 Vaccine Safety First Year Findings in Adolescents | Pediatrics | American Academy of Pediatrics ; Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Children Aged 5–11 Years — United States, October 12–January 1, 2023 | 
MMWR ; COVID-19 mRNA Vaccine Safety Among Children Aged 6 Months–5 Years — United States, June 18, 2022–August 21, 2022 | MMWR ; Safety of COVID-19 mRNA Vaccination Among Young Children in the Vaccine Safety Datalink | Pediatrics | American Academy of 
Pediatrics ; Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5-11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022 – PubMed ; Reported cases of multisystem inflammatory syndrome in children aged 
12–20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation - The Lancet Child & Adolescent Health 25 
          
        
  
                            
          Majority of COVID-19 Vaccine Reports to VAERS in Children Aged 
<12 Years Include at Least One Vaccine Administration Error 
Approximately 77% of reports in children aged 6 months-4 years and 70% of reports in children aged 5-11 years 
related to administration errors between October 21, 2021 – April 30, 2025 
Data source: https://wonder.cdc.gov 
VAERS reports may include more than one administration error type 26 
        
 
    CDC Is Expanding Its Work to Prevent Vaccine 
Administration Errors 
Vaccine Administration Protocols | CDC 27 
Evaluating Safety of COVID-19 Vaccines in Pregnant Women 
• >23,000 pregnant women CDC COVID-19 Vaccine Pregnancy Registry 
• 7 analyses 
• Ob
servational studies based on survey 
and medical record information 
• >45,000 pregnant women Vaccine Safety Datalink 
• 11 an
alyses to date 
• Cohort
, case-control, and surveillance 
evaluations 
      
 
     
   
    
  
           
28 
    
       
 
  
 
  
 
   
  
  
  
 
 
                                
                               
                                
                              
             COVID-19 Vaccine Safety During Pregnancy 
Across CDC studies, evidence shows NO increased risk of: 
Materna
l outcomes Pregnancy outcomes Infant outcomes 
 25 medically-attended  Miscarriage  Major birth defects 
adverse events  Stillbirth  Neonatal ICU admission 
 Serious adverse events  Preterm birth  Infant death 
 Pregnancy-related  Small-for-gestational age 
condi
tions 
 Maternal ICU admission 
Evaluation of Acute Adverse Events after Covid-19 Vaccination during Pregnancy | New England Journal of Medicine ; Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth — Eight Integrated Health Care 
Organizations, United States, December 15, 2020–July 22, 2021 | MMWR ; Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion | New England Journal of Medicine ; Spontaneous Abortion Following COVID-19 Vaccination During 
Pregnancy | Public Health | JAMA | JAMA Network ; COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion; Coronavirus Disease 2019 (COVID-19) Vaccination and Stillbirth in the Vaccine Safety Datalink ; 
Medically Attended Acute Adverse Events in Pregnant Women ; Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination; COVID-19 Vaccination in the First Trimester and Major Structural Birth 
Defects Among Live Births ; Accumulating Robust Evidence for Reducing Vaccine Hesitancy in Early Pregnancy—Reply 29 
        
   
  
        
  
  
       
      
    
       
  
        
    
            
                   
                     
       
   
       
       
      Address Vaccine Safety 
Tinnitus 
• Conducted data mining to assess tinnitus: 
-VAERS empirical Bayesian data mining did not find 
disproportionate reporting of tinnitus 
-VSD tree-based data mining found no signals for tinnitus 
• Taken together, findings do not support an 
inc
reased risk of tinnitus after COVID-19 vaccine 
Postmenopausal Bleeding After Coronavirus Disease 2019 (COVID-19) Vaccination: Vaccine Adverse Event Reporting System – PubMed 
Menstrual irregularities and vaginal bleeding after COVID-19 vaccination reported to v-safe active surveillance, USA in December, 2020-January, 2022: an observational cohort study – PubMed Tinnitus after COVID-19 vaccination: Findings from the vaccine adverse event reporting system and the vaccine safety datalink - ScienceDirect Examples of CDC Studies to 
Concerns from the Public 
Abnormal uterine bleeding 
• Conducted studies in VAERS, VSD, and v-safe for 
ab
normal uterine bleeding 
• VSD studies demonstrated: 
-Availability of COVID-19 vaccines was not associated 
with a change in incidence of medically-attended 
abnormal uterine or post-menopausal bleeding 
-Receipt of COVID-19 vaccine not associated with 
greater bleeding severity 
Abnormal uterine bleeding diagnoses and care following COVID-19 vaccination – ScienceDirect 
Postmenopausal bleeding after COVID-19 vaccination – PubMed 
30 
       
   
            
  
         
          
           
             
 
         
            
   
            Safety Monitoring of Death Reports Following mRNA COVID -
19 Vaccination in VAERS 
• As of May 30, 2025, there have been 19,417 domestic deaths reported to VAERS 
after COVID-19 vaccination 
• Important considerations related to evaluation of death reports in VAERS 
-FDA Emergency Use Authorizations and CDC COVID-19 Vaccination Provider Enrollment 
Agreements required healthcare provider to report all deaths following COVID-19 vaccination to 
VAERS, regardless of cause or circumstances surrounding death (requirement does not apply to 
oth
er vaccines) 
-VAERS generally cannot assess causality of adverse reports, including deaths 
• We conducted an evaluation of deaths following mRNA COVID-19 vaccination in VAERS 
thr
ough January 31, 2023 
Vaccine Adverse Event Reporting System. VAERS Reporting Information for COVID-19 Vaccines. https://vaers.hhs.gov/reportevent.html 31 
   
    
      
 
  
  
         
   
              
        
   
     
  
     
 
                  
                                
 Safety Monitoring of Death Reports Following mRNA*COVID-19 
Vaccination in VAERS – December 22, 2020 – January 31, 2023 
Deaths reported in VAERS 
CDC requests 
medical records 
Excluded 
12,849 wi
th cause of death : • 1,790 re
ports of vaccine types 17,631 do
mestic VAERS 17,579 re
ports with verified death after • Autopsy: 673 othe
r than mRNA repo
rts of death following review by CDC clinician • Death certification: 8,862 • 2,940 wi
thout cause of death COVI
D-19 vaccine • Medical records: 2,576 (52 de
termined not to be a death) info
rmation available • VAER
S report alone: 738 
* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine 
Reports to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing 32 
   
    
      
 
  
  
         
   
        
 
     
      
          
        
    
      
     
  
     
 
     
                  
                              Safety Monitoring of Death Reports Following mRNA*COVID-19 
Vaccination in VAERS – December 22, 2020 – January 31, 2023 
17,631 domestic VAERS 
reports of death following 
COVID-19 vaccine 
12,849 with cause of death : 
• Autopsy: 673 
• Death certification: 8,862 
• Medical records: 2,576 
• VAERS report alone: 738 17,579 reports with verified death after 
review by CDC clinician 
(52 determined not to be a death) 
CDC requests 
medical records 
National Center for Health Statistics 
Multiple Cause of Death Database 
Death certificates 
from U.S. residents 
Cause of death categorized 
by ICD-10 diagnostic codes Deaths reported in VAERS 
• 1,790 reports of vaccine types 
other than mRNA 
• 2,940 without cause of death information available Ex
cluded 
Deaths reported in general U.S. population 
* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine 
Rep
orts to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing 33 
   
    
      
 
  
  
         
   
      
     
      
         
        
    
      
 
   
  
    
 
   
    
         
  
     
 
     
                  
                              
                                    
 Safety Monitoring of Death Reports Following mRNA*COVID-19 
Vaccination in VAERS – December 22, 2020 – January 31, 2023 
17,631 domestic VAERS 
reports of death following 
COVID-19 vaccine 12,849 with cause of death : 
• Autopsy: 673 
• Death certification: 8,862 
• Medical records: 2,576 
• VAERS report alone: 738 17,579 reports with verified death after 
review by CDC clinician 
(52 determined not to be a death) 
National Center for Health Statistics 
Multiple Cause of Death Database Death certificates 
from U.S. residents Cause of death categorized 
by ICD-10 diagnostic codes Deaths reported in VAERS 
Observed Rate 
Number of deaths (cause-specific) 
100,000 persons vaccinated 
Within 42 days of vaccination 
Expected Rate 
Number of deaths (cause-specific) 
100,000 persons in U.S. population 
Within 42 days of vaccination • 1,790 reports of vaccine types 
other than mRNA 
• 2,940 without cause of death information available Exclud
ed 
Deaths reported in general U.S. population 
* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine 
Reports to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing Abara WE, et al. Expected Rates of Select Adverse Events After Immunization for Coronavirus Disease 2019 Vaccine Safety Monitoring | The Journal of Infectious Diseases ; Mahaux O, et al. Pharmacoepidemiological considerations in observed
‐to‐expected analyses for vaccines 
CDC requests 
medical records 
34 
         
        
                     
         
     
     
    
                 
                             
                              
                                   
                                
          Reporting Rates of Death After mRNA*COVID-19 Vaccination Were Below 
Background Rates of Death in the General U.S. Population 
The most common causes of death reported to VAERS are consistent with the leading causes of death in the U.S. population 
0 0.2 0.4 0.6 0.8 1 Observed/Expected Ratio 6 months-17 years 18-49 years 50-64 years 65+ years Observed / Expected <1: Indicates 
lower observed death rate than 
the expected rate within the post-
vaccination interval of 42 days 
* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine 
Reports to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing 
Hoyert DL, Xu J. Deaths: preliminary data for 2011. Natl Vital Stat Rep. 2012; 61:1–51 ; U.S. Centers for Disease Control and Prevention. CDC WONDER. Available at https://wonder.cdc.gov/controller/datarequest/D157 Accessed March 20, 2025 
Abara WE, et al. Expected Rates of Select Adverse Events After Immunization for Coronavirus Disease 2019 Vaccine Safety Monitoring | The Journal of Infectious Diseases ; Mahaux O, et al. Pharmacoepidemiological considerations in observed ‐to‐expected analyses for vaccines 
National Center for Health Statistics, National Vital Statistics System. Deaths: Leading Causes of Death for 2021. 73:4. Published April 8, 2024. https://www.cdc.gov/nchs/data/nvsr/nvsr73/nvsr73-04.pdf National Center for Health Statistics, National Vital Statistics System. Deaths: Leading 
Causes of Death for 2020. 72:13. Published December 5, 2023. https://www.cdc.gov/nchs/data/databriefs/db492-tables.pdf#4 35 
        
       
  
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
      
     
  
           
       
  
 
 
 
  
     
     
          
              
              
    
          
       Data From CDC’s Vaccine Safety Datalink Shows No 
Increased Risk of Death Following mRNA COVID-19 Vaccines 
36 0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1 
0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1 Dose 1 Dose 2 
Non-COVID-19 mortality 
All-cause mortality Cardiac-related mortality 
Non-COVID-19 cardiac-related mortality 
Non-COVID-19 mortality 
All-cause mortality Cardiac-related mortality 
Non-COVID-19 cardiac-related mortality 
Non-COVID-19 mortality 
All-cause mortality Cardiac-related mortality 
Non-COVID-19 cardiac-related mortality 
Non-COVID-19 mortality 
All-cause mortality Cardiac-related mortality 
Non-COVID-19 cardiac-related mortality Pfizer-BioNTech 
Moderna Ages 12 Years and Older 
Ages 65 Years and Older (Medicare Beneficiaries) 
Dose 1 Dose 2 
X axis: Relative Incidence and 95% Confidence Intervals Pfizer-BioNTech 
Moderna •2 self-controlled case series
evaluations
•No increased risk in the 28 days
after vaccination of:
-Non-COVID mortality
-All-cause mortality
-Cardiac-related mortality
-Non-COVID cardiac-related mortality
•Similar findings in VSD cohort
study of people ages 12+ years
Mortality risk after COVID-19 vaccination: A self-controlled case series study 
https://pubmed.ncbi.nlm.nih.gov/38388239/ 
A Modified Self-Controlled Case Series on Mortality Risk following Primary Series Doses of COVID-19 
Vaccines in U.S. Medicare Beneficiaries Aged 65 Years and Older - Acumen and Vaccine Safety Datalink, 
unpublished pending review at journal A safety study evaluating non-COVID-19 mortality risk following COVID-19 vaccination - PubMed 
Data from December 14, 2020 through August 11, 2021  
       
   
              
               
                       
       
       
 
 
 
       
 
    
    
Tree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink – PubMed 
Safety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink - PubMed 
37 Using Data Mining to Assess for Unexpected 
Events After COVID-19 Vaccination 
• >60,000 possible adverse events assessed in the 
70 day
s after vaccination using tree-based data 
mining of ICD-10 codes in the VSD for: 
-Primary series 
-Initial booster 
-Bivalent booster 
• No new safety concerns identified outside of 
known e
vents 
-E.g., myocarditis/pericarditis, allergic reactions, 
common local and systemic reactions 
A broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink - PubMed 
Summary 
38 
38 
       
 
   
  
 
    
 
    
   
            
        
     CDC Summary: Adverse Events Associated with mRNA 
COVID-19 Vaccines 
Occur with any vaccines: Occur with COVID-19 vaccines: 
• Local reactions • Myocarditis and pericarditis 
• S
ystemic reactions 
• Acute allergic reactions (e.g., anaphylaxis) 
• Syncope (fainting) 
• Shoulder injuries 
CDC evaluated at least 65 specific safety outcomes, conducted data mining of 
>60,000 potential outcomes for unexpected concerns, investigated numerous 
signals, and conducted many epidemiologic studies 
39 
     
    
      
 
        
     
     
      
     
                
   
40 NASEM Consensus Report on Adverse 
Effects of COVID-19 Vaccines – 2024 
• Commissioned by Health Resources and Services 
Administration (HRSA) 
• Reviewed nearly 600 studies on safety of COVID-19 vaccines 
• Concluded evidence supported causal association between mRNA COVID-19 vaccines and myocarditis 
-Evidence favors rejection of causal relationship 
between vaccination and 6 additional outcomes 
Front Matter | Evidence Review of the Adverse Effects of COVID-19 Vaccination and Intramuscular Vaccine Administration | 
The National Academies Press 
        
      
           
 
            
         
             
    
        COVID-19 Vaccines Have Been Evaluated Under the Most 
Extensive Safety Monitoring Program in U.S. History 
• Safety surveillance identified and characterized the risk of myocarditis after mRNA 
COVID-19 vaccination 
• No other risks confirmed in the current U.S.-licensed vaccines except those seen with other vaccines (e.g., local and systemic reactions, allergic reactions) 
• CDC continues to prioritize the monitoring of COVID-19 vaccine safety, with at least 30 ongoing studies or activities 
• CDC continues to monitor the safety of COVID-19 vaccines 
41