medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023.

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Safety of Monovalent BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and

NVX-CoV2373 (Novavax) COVID-19 Vaccines in US Children Aged 6 months to 17
years
Mao Hu, BS1; Azadeh Shoaibi, PhD, MHS2; Yuhui Feng, MS1; Patricia C. Lloyd, PhD, ScM2; Hui Lee
Wong, PhD, MSc2; Elizabeth R. Smith, BS1; Kandace L. Amend, PhD3; Annemarie Kline, MS4; Daniel
C. Beachler, PhD, MPH5; Joann F. Gruber, PhD2; Mahasweta Mitra, MPH1; John D. Seeger, DrPH,
PharmD3; Charlalynn Harris, MPH, PhD4; Alex Secora, PhD6; Joyce Obidi, PhD2; Jing Wang, BA1;
Jennifer Song, MA, MURP3; Cheryl N. McMahill-Walraven4; Christian Reich, MD, PhD6; Rowan
McEvoy, BS1; Rose Do, MD1; Yoganand Chillarige, MPA1; Robin Clifford, MS, BS3; Danielle D
Cooper4; Richard Forshee, PhD2; Steven A. Anderson, PhD, MPP2

1
Acumen LLC, Burlingame, CA, USA
2
US Food and Drug Administration, Silver Spring, MD, USA
3
Optum Epidemiology, Boston, MA, USA
4
Carelon Research, Wilmington, DE, USA
5
CVS Health/Aetna, Blue Bell, PA, USA
6
IQVIA, Falls Church, VA, USA

Corresponding Author:
Patricia C. Lloyd, PhD, ScM
Health Statistician
Office of Biostatistics and Pharmacovigilance
Center for Biologics Evaluation and Research
U.S. Food & Drug Administration
10903 New Hampshire Ave., Building 71
Silver Spring, MD 20993
Email: [email protected]

Word Count: 2,964

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NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

Key Points

Question

Did active monitoring detect statistical signals for health outcomes following monovalent COVID-19

vaccination in the US children aged 6 months to 17 years?

Findings

In this study including 4,102,106 vaccinated enrollees from three commercial claims databases,

myocarditis or pericarditis signaled after BNT162b2 (12-17 years) and a new signal was detected for

seizures/convulsions after BNT162b2 (2-4 years) and mRNA1273 COVID-19 vaccinations (2-5 years).

Meaning

Near real-time monitoring of vaccines can rapidly identify potential safety concerns. While the

myocarditis or pericarditis signal is consistent with existing evidence, the new seizures/convulsions

signal should be interpreted cautiously given study limitations.

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Abstract

Importance

Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare

outcomes that may not be identified in prelicensure trials.

Objective

To conduct near real-time monitoring of health outcomes following COVID-19 vaccination in the

United States (US) pediatric population aged 6 months to 17 years.

Design

We evaluated 21 pre-specified health outcomes; 15 were sequentially tested through near real-time

surveillance, and 6 were monitored descriptively within a cohort of vaccinated children. We tested for

increased rate of each outcome following vaccination compared to a historical comparator cohort.

Setting

This population-based study was conducted under the US Food and Drug Administration public health

surveillance mandate using three commercial claims databases.

Participants

Children aged 6 months to 17 years were included if they received a monovalent COVID-19 vaccine

dose before early 2023 and had continuous enrollment in a medical health insurance plan from the start

of an outcome-specific clean window to the COVID-19 vaccination dose.

Exposure

Exposure was defined as receipt of a monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-

19 vaccine dose. The primary analysis evaluated dose 1 and dose 2 combined, and secondary analyses
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evaluated each dose separately. Follow-up time was censored at death, disenrollment, end of risk

window, end of study period, or a subsequent dose administration.

Main Outcomes

Twenty-one prespecified health outcomes.

Results

The study included 4,102,016 enrollees aged 6 months to17 years. Thirteen of 15 outcomes sequentially

tested did not meet the threshold for a statistical signal. In the primary analysis, myocarditis or

pericarditis signals were detected following BNT162b2 vaccine in children aged 12-17 years old and

seizures/convulsions signals were detected following vaccination with BNT162b2 and mRNA-1273 in

children aged 2-4/5 years. However, in a post-hoc sensitivity analysis, the seizures/convulsions signal

was sensitive to background rates selection and was not observed when 2022 background rates were

selected instead of 2020 rates.

Conclusions and Relevance

Of the two signaled outcomes, the myocarditis or pericarditis signals are consistent with previously

published reports. The new signal detected for seizures/convulsions among younger children should be

further investigated in a robust epidemiological study with better confounding adjustment.

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All rights reserved. No reuse allowed without permission.

Introduction

Three vaccines against COVID-19 are currently available for use in children in the United States (US)

including the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA-1273) COVID-19 mRNA vaccines

for those aged 6 months to 17 years and the protein-based Novavax COVID-19 vaccine (NVX-

CoV2373) for those aged 12 to 17 years.1-3 As of May 2023, the Centers for Disease Control and

Prevention (CDC) reported 31.78 million children had received at least one COVID-19 vaccine dose

and 26.2 million children had completed the primary series out of approximately 73 million children

aged 6 months to 17 years in the US.4 The US Food and Drug Administration (FDA), utilizing the

Biologics Effectiveness and Safety (BEST) Initiative, has been monitoring the safety of COVID-19

vaccines in children since their authorization by applying a near real-time monitoring framework to

evaluate the safety of COVID-19 vaccines. This process is a signal detection or screening method and

the first step in safety monitoring of these vaccines. This framework is designed to be sensitive enough

to rapidly detect less common safety signals. However, results of such study design do not establish a

causal relationship between the vaccines and health outcomes and need to be interpreted with caution

because of the limited adjustment for confounding and other forms of bias.

The BEST analysis of COVID-19 vaccines in children initially focused on the BNT162b2 COVID-19

monovalent vaccine authorized for use in children aged 5 to 17 years. Surveillance has since been

expanded as additional pediatric age groups and vaccine brands received authorization through late

2022. Results of the initial, more limited, safety surveillance in children have been previously

published.5 In this report, we present results from the expanded monitoring of health outcomes in

children after exposure to the ancestral monovalent COVID-19 vaccines in the US targeting the original

COVID-19 strain.

Methods

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Study Objective

This study evaluated 21 pre-specified health outcomes after exposure to BNT162b2, mRNA-1273, or

NVX-CoV2373 monovalent COVID-19 vaccines in children 6 months to 17 years old by applying a

near real-time monitoring framework using health care data from three commercial claims databases in

the US. Fifteen outcomes underwent sequential testing, and 6 outcomes were only monitored

descriptively due to lack of historical rates.

Data Sources

The study used commercial administrative claims data from Optum, Carelon Research, and CVS Health

containing longitudinal medical and pharmacy claims data supplemented with vaccination data from

participating local and state Immunization Information Systems (IIS) (Supplemental Table 1).6

Study Population and Period

The study included pediatric enrollees aged 6 months to 17 years who received a monovalent COVID-

19 vaccine from the earliest date of its Emergency Use Authorization by age group through April 2023

(Optum), March 2023 (Carelon Research), and February 2023 (CVS Health) (Supplemental Table 2).

The surveillance concluded on these respective dates because of limited accrual of exposures and health

outcomes. The sequential analyses for most outcomes did not reach the expected number of events that

was pre-specified based on anticipated vaccination uptake in a 6-month period post-authorization of

individual vaccine products. Another contributing factor to halting surveillance was the de-authorization

of the original monovalent mRNA-1273 and BNT162b2 doses for persons of all ages on April 18,

2023.7

The inclusion criteria for the study included enrollment on the vaccination date and continuous

enrollment in a participating medical health insurance plan from the start of an outcome-specific clean

window to the COVID-19 vaccination date so that only new incident diagnosis of an outcome in the
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post-vaccination risk window would contribute to the analysis (Supplemental Table 3).

Exposures and Follow Up

Exposure was defined as the receipt of a BNT162b2, mRNA-1273, or NVX-CoV2373 monovalent

COVID-19 vaccine dose identified using brand and dose-specific Current Procedural

Terminology/ Healthcare Common Procedure Coding System codes 8 and National Drug Codes

(Supplemental Table 4). Dose number was assigned based on the chronological order in which

vaccinations were observed since administration codes were not available in pharmacy claims. The

primary analyses included all follow-up time accrued after dose 1 and dose 2 combined. Secondary

analyses included stratification by dose number and follow-up time accrued after the individual dose

(including monovalent third/booster doses) through censoring at subsequent vaccination, death,

disenrollment, end of risk window, or end of study period.

Health Outcomes

Twenty-one pre-specified health outcomes were defined using claims-based algorithms9-10. Outcomes

were selected through clinical consultation and literature review. Fifteen health outcomes were assessed

using sequential testing comparing rates to historical outcome rates (additional information on historical

rates below), and 6 were only monitored descriptively due to lack of historical rates.10 The outcome

myocarditis, pericarditis, or co-occurring myocarditis and pericarditis (hereafter referred to as

myocarditis/pericarditis) was assessed using four different definitions with varying risk windows and

care settings (included in Supplemental Table 3) based on evidence from prior surveillance efforts and

clinical input.

Descriptive Monitoring

We estimated outcome rates in the vaccinated population stratified by age, sex, region, urban/rural

status, data source, and vaccine brand on a monthly basis.

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Sequential Testing

Monthly sequential testing was conducted using the Poisson Maximized Sequential Probability Ratio

Test (PMaxSPRT) to detect statistical signals by generating the incidence rate ratio (IRR) comparing

outcome rates following vaccination to database-specific historical (expected) rates for 15 health

outcomes.11

We estimated annual historical rates for 2019 and 2020 as well as during the COVID-19 pandemic

between April and December 2020. Historical rates were adjusted for claims processing delay to account

for observation delay and standardized by age and sex where case counts permitted.12 Selection of the

historical comparator rate was based on the overlap between the 95% confidence intervals (CI) for the

periods prior to and during the COVID-19 pandemic. If rates in these two historical periods differed

substantially, we selected either the minimum or more stable rate as a more conservative approach.

Tests were stratified by age based on age-group-specific authorizations by vaccine brand as well as

availability of background rates using historical comparator data. For BNT162b2, this included ages 6

months-4 years, 6 months-1 year and 2-4 years (for seizure/convulsions only), 5-11 years, 12-15 years,

and 16-17 years. For mRNA-1273, this included 6 months-5 years, 6 months-1 year and 2-5 years (for

seizure or convulsions only), 6-11 years, 12-15 years, and 16-17 years. For NVX-CoV2373, the age

groups were 12-15 years and 16-17 years.

Sequential testing for each outcome commenced when a minimum of three cases accrued in the risk

window. One-tailed tests were used with the null hypothesis that the observed rate was no greater than

the historical comparator rate beyond a pre-specified test margin for each outcome-dose-age group

being sequentially tested, with an alpha level of 1%. A stringent alpha level was selected to increase the

specificity of signals detected from testing multiple outcomes across different analyses. The log

likelihood ratio was calculated comparing the likelihood of the observed IRR and the null hypothesis.

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At each test, if the log likelihood ratio exceeded a pre-specified critical value, the null hypothesis was

rejected, and a signal was declared. Surveillance continued until a signal was detected, the pre-specified

maximum surveillance length was reached, or the end of study period was reached.10

Signal Characterization

Signal characterization was conducted after a signal was identified to provide data quality assessment.13

We conducted quality checks to rule out database errors or changes in the patterns of diagnosis codes

used to identify events in the study period; estimated the relative risk of outcomes within demographic

strata by age and sex; examined the timing of outcomes occurrence during the pre-specified risk

window; and assessed whether the signal was sensitive to changes in background rates selection by

conducting a post-hoc sensitivity analysis using the updated 2022 background rates as the historical

comparator in sequential testing.

Medical Record Review

Medical record review was conducted for the myocarditis/pericarditis outcome following identification

of a signal. Brighton Collaboration case definitions were used to adjudicate cases.14 Records meeting the

confirmed or probable Brighton classifications were considered true myocarditis/pericarditis cases for

the validation analyses.

Results

Descriptive Monitoring

A total of 8,444,355 monovalent COVID-19 vaccine doses were administered to 4,102,016 enrollees

aged 6 months -17 years (Figure 1). This included 8,121,591 BNT162b2 (Dose 1: 3,843,778, Dose 2:

3,235,442, Dose 3/ Monovalent Booster: 1,033,036 and Unknown/Unclear: 9,335), and 322,628

mRNA-1273 doses (Dose 1: 173,857, Dose 2: 140,734, Dose 3/Monovalent Booster: 5,284 and

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Unknown/Unclear: 2,753) administered to children aged 6 months-17 years, as well as 136 NVX-

CoV2373 doses (Dose 1: 63, Dose 2: 43, Dose 3/Monovalent Booster and Unknown/Unclear: 30)

administered to children aged 12-17 years (Table 1a). Demographic characteristics of the vaccinated

population except age reported at first dose were largely similar across vaccine brands. While majority

(93.4%) of BNT162b2-vaccinated individuals were 5 years old and older; majority (97.6%) of mRNA-

1273-vaccinated individuals were younger than 5 years old. Across all vaccine brands, 2,058,142

(50.2%) were males and 3,901,370 (95.2%) lived in an urban area (Table 1b). We observed low case

counts for outcomes that were monitored descriptively only (<80 cases of any given outcome in all three

databases combined) (Supplemental Table 5).

Sequential Testing

Among 15 outcomes that were sequentially tested, two outcomes met the statistical threshold for a

signal including myocarditis/pericarditis in ages 12-15 and 16-17 years, and seizures/convulsions in

ages 2-4/5 years.

Myocarditis/pericarditis signaled for all definitions in the primary analysis following BNT162b2

COVID-19 vaccination among children aged 12-15 and 16-17 years in all three databases. Additionally,

dose-specific signals for one or more definitions of the outcomes were detected in ages 12-17 years

following dose 1, dose 2, and dose 3 of BNT162b2 vaccine in at least one of the three databases (Table

2).

In the primary analysis, seizures/convulsions met the statistical threshold for a signal in children aged 2-

4 years following BNT162b2 vaccination in all three databases, and in children aged 2-5 years

following mRNA-1273 vaccination in two of the three databases. Dose-specific signals for

seizures/convulsions were detected in two of the three databases following dose 1 and dose 2

BNT162b2 vaccination in ages 2-4 years and following dose 2 mRNA-1273 vaccination in ages 2-5

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years (Table 2).

Sequential testing did not initiate for any of the 15 outcomes for mRNA-1273 in ages 5-17 years and

NVX-CoV2373 in ages 12-17 years, because no outcomes were observed in any databases.

Signal Characterization

Since myocarditis/pericarditis is a known adverse outcome following COVID-19 mRNA vaccinations,

further signal characterization activities were not conducted. In the evaluation of the

seizures/convulsions signal among children aged 2-4/5 years, none of the pre-specified data quality

checks, including claims duplication, timing of events within pre-specified risk window, and IRR

estimates, raised any data quality concerns.

There were 72 observed seizures/convulsions cases among children aged 2-4/5 years and >50% of these

cases met the definition of febrile seizures. No differences in rates of seizures/convulsions by sex were

identified. The timing of cases did not indicate substantial clustering with cases distributed across the 0-

7-day risk window; 31.9% of the seizures/convulsions cases occurred within the 0-1 days following

COVID-19 vaccination. The median time between vaccination and diagnosis of seizures/convulsions

was 2 days. (Supplemental Figure 1).

The seizures/convulsions signal was sensitive to changes in the selection of comparator rates.

Evaluation of the annual background rate of seizures/convulsions indicated that the rates used in the

primary analyses (2020) were substantially lower than rates in 2022. Background rates in 2022 ranged

from approximately 2.2-2.4 times the 2020 rates across three databases (Supplemental Table 6). A post-

hoc sensitivity analysis using 2022 background rates as the comparator in sequential testing did not

identify any seizures/convulsions signals.

Medical Record Review

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Of the 153 cases of myocarditis/pericarditis after COVID-19 vaccination among children aged 12-17

years, medical record review was conducted for a sample of 40 cases whose records could be obtained.

Twenty-nine of these cases (72.5%) were confirmed as true cases of myocarditis/pericarditis, of which

27 patients were male, and 19 were hospitalized with a median length of hospital stay of 2 days

(interquartile range: 1, 3). The median time from vaccination to presentation of myocarditis/pericarditis

event was 3 days (interquartile range: 2, 5). Medical record review and further validation efforts for

seizures/convulsions are currently underway.

Discussion

Our near real-time monitoring of 21 pre-specified health outcomes following monovalent COVID-19

vaccines detected signals for myocarditis/pericarditis in the age group 12-17 years and

seizures/convulsions in the age group 2-4/5 years. We did not detect signals for other outcomes that

were sequentially tested.

The myocarditis/pericarditis signal is consistent with peer-reviewed publication reports demonstrating

an elevated risk of this outcome following mRNA vaccines among younger males aged 12 to 29

years.15-17 Myocarditis/pericarditis is a rare event with a reported average incidence of 39.3 cases per

one million vaccine doses administered in children aged 5-17 years within 7 days after BNT162b2

vaccination.18-19 We did not detect a signal for myocarditis/pericarditis in children younger than 12

years old which is consistent with reports from other surveillance systems.20-21

The seizures/convulsions signal in children aged 2-4/5 years has not been previously reported for this

age group in active surveillance studies of mRNA COVID-19 vaccines. However, there are reports from

the Vaccine Adverse Events Reporting System (VAERS) database which is a passive reporting system

and has limitations. In an analysis of VAERS data, only 8 seizures were identified following

approximately one million mRNA vaccinations through August 2022 in the age group 6 months to 5

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years. Six of the 8 seizures were afebrile on medical evaluation.22 Pre-licensure vaccine safety data

indicate that among young children, seizures/convulsions following mRNA COVID-19 vaccines are

rare; clinical trial of 3,013 BNT162b2 vaccine recipients in children aged 6 months to 4 years reported

only 5 febrile convulsions cases and only one of those (in a 6-month-old participant) was considered

possibly related to the vaccine or may also have been caused by a concurrent viral infection.23 Among

studies conducted in children with childhood epilepsy (<18 years), no increased risk of medically

attended seizures was identified following immunization with COVID-19 vaccines. Seizure risk after

COVID-19 vaccination was lower in children who were seizure free for more than six months before

vaccination. However, the incidence of general adverse events after vaccination was low with no severe

adverse events recorded. 24-25 Generally, there is limited evidence linking the mRNA COVID-19

vaccines to a seizure onset among vaccinated children aged 2-4/5 years.

The new seizures/convulsions signal observed in our study should be interpreted with caution and

further investigated in a more robust epidemiological study. Our study utilized a broad

seizures/convulsions outcome definition with a 0-7-day risk window because of its applicability to older

children. However, in children younger than 5 years, vaccine-related seizures typically manifest as a

febrile seizure.26 Although the majority of seizures/convulsions cases met the febrile seizure definition,

there was no statistically significant clustering observed at days 0-1. Since febrile seizures can be

common in young children for a variety of reasons; the analysis may have identified febrile seizures

unrelated to the vaccination later in the risk window.

The post-hoc sensitivity analyses using the 2022 background rates as comparators in sequential testing

did not yield any seizures/convulsions signals which suggest that our results are sensitive to comparator

rate selection. The decision to use 2020 seizures/convulsions rates as comparators was to maximize

sensitivity in the primary analysis. However, seizures/convulsions rates in this age group in 2022 were

twice as high as 2020 rates. There could be a couple of potential reasons for elevated outcome rates in
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2022 compared to 2020. First, there was an increased incidence of respiratory infections (influenza and

respiratory syncytial virus) which are shown to be associated with febrile seizure in younger children,

during the study period (mid-2022 to mid-2023) compared to 2020.27-30 Second, in 2020, there were

likely fewer emergency department visits for seizure-related events compared to 2022 because of

COVID-19 pandemic healthcare resource limitations.31

Our study has a number of strengths. First, the study included a large, geographically diverse

population from three US commercial health insurance databases. Due to availability of more complete

information from claims supplemented with IIS data and a short data lag from health encounters, we

monitored monovalent COVID-19 vaccines safety in a near real-time manner. Additionally, a subset of

the identified myocarditis/pericarditis cases were confirmed through medical record review.

The study also has some limitations. We used a near–real-time surveillance method which may be

sensitive to comparator rate selection and does not include controlling for bias and confounding.

Therefore, results from this study do not establish a causal relationship between the vaccines and health

outcomes, and signals should be further evaluated. Secondly, this study only includes data from a

commercially insured pediatric population and may not be nationally representative. Furthermore, the

study may have limited power to detect small increases in risk of outcomes in certain subgroups or in

the cases of more recently authorized vaccines, such as NVX-CoV2373 in children aged 12-17 years as

well as mRNA-1273 in those aged 5-17 years.

Conclusion

Our study detected a signal for myocarditis/pericarditis in older children which is consistent with

existing literature, and a new signal for seizures/convulsions in young children that is being further

evaluated in a more robust study. FDA concludes that the known and potential benefits of COVID-19

vaccination outweigh the known and potential risks of COVID-19 infection. This study was conducted

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under the FDA BEST Initiative which plays a major role in the larger US federal government vaccine

safety monitoring efforts and further supports regulatory decision-making regarding COVID-19

vaccines.

Acknowledgements

Funder: The US Food and Drug Administration provided funding for this study and contributed as

follows: led the design of the study, interpretation of the results, writing of the manuscript, decision to

submit, and made contributions to the coordination of data collection and analysis of the data.

Disclosures:

Annemarie Kline, Cheryl McMahill-Walraven, Djeneba Audrey Djibo worked on grants, subcontracts,

or contracts from Harvard Pilgrim Health Care Institute, Brown University (National Institute on Aging/

IMPACT Collaboratory), Reagan Udall Foundation for the FDA, Academy of Managed Care

pharmacy’s Biologics and Biosimilar Collective Intelligence Consortium (BBCIC), TherapeuticsMD,

Reachnet (Louisiana Public Health Institute), IQVIA, Pfizer, Carelon Research (formerly Healthcore),

and Patient Centered Outcomes Research Institute as employees of CVS Health and report stock or

stock options from CVS Health; Carelon Research; Kandace Amend, Robin Clifford, John Seeger, and

Jennifer Song reports stock or stock options in UnitedHealth Group; Daniel C. Beachler is an employee

of Carelon Research who has previously contracted with Pfizer Inc. for separate projects. No other

authors report relevant disclosures.

Additional Contributions: We thank Tainya C. Clarke, Sylvia Cho and Carla E. Zelaya of the US Food

and Drug Administration; Anchi Lo, Bing Lyu, Nimesh Shah, Derek Phan, Gyanada Acharya,

Kamakshi Sirpal, Laurie Feinberg, Lloyd Marks, Minisha Kochar, Sandia Akhtar, Shruti Parulekar,

Stella Zhu, William (Trey) Minter, Yeerae Kim, Yixin Jiao, and Zhiruo (Cassie) Wan of Acumen;

Nancy B Shaik, Ana M Martinez-Baquero, Smita Bhatia, Vaibhav Sharma, Carla Brannan of CVS

Health and Charlalynn Harris and Danielle Cooper formerly CVS Health; Shiva Vojjala, Ramya Avula,

15
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Shiva Chaudhary, Shanthi P Sagare, Ramin Riahi, Navyatha Namburu, and Grace Stockbower of

Carelon Research; Michael Goodman, Michael Bruhn, and Ruth Weed of IQVIA; Grace Yang, Sarah

Sargen, Alexandra Stone, Wafa Tarazi, Megan Ketchell, Kathryn Federici, Amaka Ume, Emily Myers,

Eli Wolter, Jackson Slaney, Bobby Smith, Lauren Peetluk, and Elizabeth Bell of Optum.

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References
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 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
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Table 1a. Vaccine Dose Counts for Monovalent BNT162b2, mRNA-1273, NVX-CoV2373 COVID-19
Vaccines Administered to the Pediatric Population, All Data Sourcesa

BNT162b2 mRNA-1273 NVX-CoV2373

Vaccine Dose
N % N % N %
Total 8,121,591 100 322,628 100 136 100
Dose 1 3,843,778 47.33 173,857 53.89 63 46.32
Dose 2 3,235,442 39.84 140,734 43.62 43 31.62
Dose 3/Monovalent Booster 1,033,036 12.72 5,284 1.64 § §
Unknown/Unclear 9,335 0.11 2,753 0.85 § §
a
Combines Optum data through 4/2023, Carelon Research data through 3/2023, CVS Health data through 2/2023
§
Cell sizes 1-10 and cells that can be used to back-calculate small cell sizes were masked for confidentiality

22
 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

Table 1b. Characteristics of Pediatric Population Receiving Monovalent BNT162b2, mRNA-1273, and
NVX-CoV2373 COVID-19 Vaccines, All Data Sources

BNT162b2 mRNA-1273 NVX-CoV2373 Multiple Brands

Patient Characteristics#
N % N % N % N %
Total No. Persons
3,920,563 100 176,427 100 53 100 4,973 100
Vaccinated
Age at First Dose (y)
6 months-4/5* 256,958 6.55 172,161 97.58 0 0.00 2,299 46.23
5/6-11* 1,558,895 39.76 1,687 0.96 0 0.00 1,471 29.58
12-15 1,389,351 35.44 1,420 0.80 27 50.94 945 19.00
16-17 715,359 18.25 1,159 0.66 26 49.06 258 5.19
Sex
Female 1,954,260 49.85 86,588 49.08 24 45.28 2,521 50.69
Male 1,965,853 50.14 89,808 50.90 29 54.72 2,452 49.31
Missing/Unknown 450 0.01 31 0.02 0 0.00 0 0.00
Urban/Rural
Rural 191,550 4.89 4,465 2.53 § § § §
Urban 3,724,798 95.01 171,771 97.36 50 94.34 4,751 95.54
Missing/Unknown 4,215 0.11 191 0.11 § § § §
United States Department of Health and Human Services (HHS) Region
1: CT, ME, NH, RI, VT 252,282 6.43 15,436 8.75 § § 287 5.77
2: NJ, NY, PR, VI 481,296 12.28 25,927 14.70 § § 1,844 37.08
3: DE, DC, MD, PA, VA, 12.34 § § 9.15
421,390 10.75 21,765 455
WV
4: AL, FL, GA, KY, MS, NC, 9.56 § § 10.52
610,942 15.58 16,869 523
SC, TN
5: IL, IN, MI, MN, OH, WI 644,718 16.4 24,061 13.64 § § 465 9.35
6: AR, LA, NM, OK, TX 330,374 8.43 11,142 6.32 § § 263 5.29
7: IA, KS, MO, NE 159,328 4.06 6,401 3.63 § § § §
8: CO, MT, ND, SD, UT, 3.97 § § 4.08
168,549 4.30 6,998 203
WY
9: AZ, CA, HI, NV, AS, MP, 21.20 § § 12.49
720,576 18.38 37,394 621
FM, GU, MH, PW
10: AK, ID, OR, WA 127,558 3.25 10,260 5.82 § § 203 4.08
Missing/Unknown 3,550 0.09 174 0.10 0 0.00 § §
Facility/Provider Type
Hospital 194,886 4.97 11,492 6.51 § § § §
Office 1,115,926 28.46 125,781 71.29 § § 3,559 71.57
Pharmacy 1,610,036 41.07 9,940 5.63 32 60.38 337 6.78
Skilled Nursing Facility § § 0 0.00 0 0.00 0 0.00
Home Health Agency § § 73 0.04 0 0.00 § §
Mass Immunization Center 110,794 2.83 2,448 1.39 § § 121 2.43
Other 135,842 3.46 3,851 2.18 § § 151 3.04
Missing/Unknown 751,900 19.18 22,842 12.95 § § 710 14.28

23
 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

Combines Optum data through 4/2023, Carelon Research data through 3/2023, CVS Health data through 2/2023
#
Patient characteristics were assessed at the time of first vaccine dose which was either Dose1 or Dose 2 depending on the dose that met
EUA-specific dose eligibility criteria; persons who received a different brand of vaccine from their Dose 1 are categorized in the
"Multiple Brands" category
§
Cell sizes 1-10 and cells that can be used to back-calculate small cell sizes were masked for confidentiality
Percentages may not sum up to 100% due to rounding.
* Children aged 6 months – 4 years that were vaccinated with BNT162b2 COVID-19 vaccine are included in 6 months – 4/5 years age
group; children aged 6-months – 5 years that were vaccinated with mRNA1273 COVID-19 vaccine are included in the 6 months – 4/5
years age group. Children aged 5 – 11 years that were vaccinated with BNT162b2 COVID-19 vaccine are included in the 5/6 – 11 years
age group; children aged 6 – 11 years that were vaccinated with mRNA1273 COVID-19 vaccine are included in the 5/6 -11 years age
group.

24
Figure 1. Distribution of Monovalent Doses of BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 Vaccines Administered Over
Time by Age Group, All Data Sources

Combines Optum data through 4/2023, Carelon Research data through 3/2023, CVS Health data through 2/2023
 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

Table 2. Sequential Testing Results for the Pediatric Population Receiving BNT162b2 or
mRNA-1273 Monovalent COVID-19 Vaccines Stratified by Vaccine dose and
Outcome

BNT162b2 mRNA-1273
Age
Outcome Dose Group No. No. Person- No. Person- Signal
Signal No.
(years) Vaccine Outcom Time Outcome Time Status
Status* Doses
Doses es (Days) s (Days) *
6months(
454,003 § 903,139 NT 304,501 § 606,089 NT
m)-4/5
Dose 1
+ Dose 5/6-11 2,715,842 § 5,428,277 NS 1,687 0 3,346 NT
2 12-15 2,444,395 § 4,887,562 NS 1,558 0 3,093 NT
16-17 1,245,735 § 2,490,728 NT 1,315 0 2,604 NT
6m-4/5 248,106 § 493,859 NT 166,491 0 331,645 NT
5/6-11 1,467,128 § 2,932,681 NT 1,068 0 2,120 NT
Dose 1
12-15 1,309,249 § 2,617,844 NS 957 0 1,896 NT
Anaphylaxis 16-17 676,147 § 1,351,857 NT 834 0 1,646 NT
6m-4/5 205,897 § 409,280 NT 138,010 § 274,444 NT
5/6-11 1,248,714 § 2,495,596 NT 619 0 1,226 NT
Dose 2
12-15 1,135,146 § 2,269,718 NT 601 0 1,197 NT
16-17 569,588 0 1,138,871 NT 481 0 958 NT
6m-4/5 102,335 0 204,292 NT 3,391 0 6,671 NT
5/6-11 269,600 0 538,724 NT 725 0 1,448 NT
Dose 3
12-15 383,763 § 767,272 NT 589 0 1,178 NT
16-17 237,024 § 473,794 NT 320 0 640 NT
6m-4/5 351,986 § 11,874,618 NT 241,915 § 8,789,224 NT
Dose 1 5/6-11 2,213,650 206 72,789,318 NS 1,212 0 43,060 NT
+ Dose
2 12-15 2,035,023 302 66,600,250 NS 1,187 0 42,059 NT
16-17 1,043,311 166 34,406,004 NS 1,013 0 34,656 NT
6m-4/5 190,648 § 5,463,829 NT 131,372 § 4,385,416 NT
5/6-11 1,182,865 92 30,910,940 NS 755 0 26,302 NT
Dose 1
12-15 1,078,396 130 27,055,551 NS 703 0 23,821 NT
16-17 559,908 74 14,413,948 NS 632 0 20,186 NT
Appendicitis
6m-4/5 161,338 § 6,410,789 NT 110,543 § 4,403,808 NT
5/6-11 1,030,785 114 41,878,378 NS 457 0 16,758 NT
Dose 2
12-15 956,627 172 39,544,699 NS 484 0 18,238 NT
16-17 483,403 92 19,992,056 NS 381 0 14,470 NT
6m-4/5 83,010 § 3,397,223 NT 2,845 0 92,282 NT
5/6-11 239,487 27 9,790,542 NS 645 0 23,859 NT
Dose 3
12-15 352,339 54 14,545,967 NS 532 0 20,146 NT
16-17 214,951 41 8,754,099 NS 285 0 10,536 NT
Bell's Palsy 6m-4/5 410,400 § 14,065,149 NS 277,737 § 10,222,194 NS

26
 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

Dose 1 5/6-11 2,485,011 35 81,704,667 NS 1,467 0 53,845 NT

+ Dose 12-15 2,223,492 56 72,869,846 NS 1,410 0 51,392 NT
2 16-17 1,129,439 24 37,292,252 NS 1,216 0 43,061 NT
6m-4/5 221,585 § 6,444,275 NT 150,082 § 5,063,381 NT
5/6-11 1,334,662 14 35,013,473 NS 916 0 32,855 NT
Dose 1
12-15 1,179,765 18 29,755,101 NS 849 0 29,484 NT
16-17 607,786 § 15,737,104 NS 760 0 25,173 NT
6m-4/5 188,815 § 7,620,874 NT 127,655 § 5,158,813 NT
5/6-11 1,150,349 22 46,691,194 NS 551 0 20,990 NT
Dose 2
12-15 1,043,727 38 43,114,745 NS 561 0 21,908 NT
16-17 521,653 § 21,555,148 NS 456 0 17,888 NT
6m-4/5 96,939 § 3,984,353 NT 3,233 0 110,964 NT
5/6-11 259,078 § 10,618,052 NS 699 0 27,077 NT
Dose 3
12-15 370,606 16 15,297,175 NS 562 0 22,080 NT
16-17 229,588 § 9,335,942 NS 310 0 12,020 NT
#
6m-4/5 244,267 0 6,241,793 NT 81,661 0 2,219,079 NT
Dose 1 5-6/11 #
2,215,973 § 55,992,946 NT 621 0 16,404 NT
+ Dose
2 12-15 2,038,360 § 51,169,805 NT 1,188 0 31,617 NT
16-17 1,045,098 § 26,329,445 NT 1,016 0 26,702 NT
#
6m-4/5 131,743 0 3,201,944 NT 43,906 0 1,196,821 NT
#
5-6/11 1,184,106 § 27,642,091 NT 398 0 10,492 NT
Dose 1
Common Site 12-15 1,080,146 0 24,623,090 NT 704 0 18,802 NT
Thrombosis 16-17 560,874 § 12,913,395 NT 634 0 16,526 NT
with #
Thrombocytop 6m-4/5 112,524 0 3,039,849 NT 37,755 0 1,022,258 NT
enia† 5-6/11 #
1,031,867 0 28,350,855 NT 223 0 5,912 NT
Dose 2
12-15 958,214 § 26,546,715 NT 484 0 12,815 NT
16-17 484,224 § 13,416,050 NT 382 0 10,176 NT
#
6m-4/5 59,404 0 1,638,795 NT 778 0 19,250 NT
#
5-6/11 239,716 § 6,602,510 NT 352 0 9,147 NT
Dose 3
12-15 352,878 0 9,765,325 NT 533 0 14,234 NT
16-17 215,309 0 5,886,780 NT 285 0 7,596 NT
6m-4/5 351,932 § 9,020,709 NT 241,877 0 6,579,967 NT
Dose 1 5/6-11 2,215,893 § 55,988,930 NT 1,212 0 32,099 NT
+ Dose
2 12-15 2,038,235 § 51,163,432 NS 1,188 0 31,617 NT
16-17 1,044,870 § 26,321,797 NS 1,016 0 26,702 NT
Deep Vein 6m-4/5 190,617 0 4,651,184 NT 131,352 0 3,581,264 NT
Thrombosis 5/6-11 1,184,060 § 27,640,017 NT 755 0 20,038 NT
Dose 1
12-15 1,080,081 § 24,620,103 NS 704 0 18,802 NT
16-17 560,752 § 12,909,608 NS 634 0 16,526 NT
6m-4/5 161,315 § 4,369,525 NT 110,525 0 2,998,703 NT
Dose 2
5/6-11 1,031,833 0 28,348,913 NT 457 0 12,061 NT

27
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(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

12-15 958,154 § 26,543,329 NT 484 0 12,815 NT

16-17 484,118 § 13,412,189 NT 382 0 10,176 NT
6m-4/5 83,015 0 2,291,244 NT 2,845 0 68,640 NT
5/6-11 239,708 0 6,601,838 NT 648 0 17,106 NT
Dose 3
12-15 352,852 § 9,763,925 NT 533 0 14,234 NT
16-17 215,265 § 5,885,237 NT 285 0 7,596 NT
6m-4/5 352,017 § 8,897,561 NT 241,928 0 6,501,186 NT
Dose 1 5/6-11 2,215,973 § 55,933,013 NT 1,212 0 30,713 NT
+ Dose
2 12-15 2,038,363 0 51,163,245 NT 1,188 0 30,749 NT
16-17 1,045,113 0 26,325,916 NT 1,018 0 25,832 NT
6m-4/5 190,665 § 4,597,312 NT 131,380 0 3,546,479 NT
5/6-11 1,184,106 § 27,614,907 NT 755 0 19,448 NT
Dose 1
12-15 1,080,148 0 24,619,938 NT 704 0 18,402 NT
Disseminated 16-17 560,883 0 12,911,429 NT 635 0 15,982 NT
Intravascular
Coagulation 6m-4/5 161,352 0 4,300,249 NT 110,548 0 2,954,707 NT
5/6-11 1,031,867 § 28,318,106 NT 457 0 11,265 NT
Dose 2
12-15 958,215 0 26,543,307 NT 484 0 12,347 NT
16-17 484,230 0 13,414,487 NT 383 0 9,850 NT
6m-4/5 83,022 0 2,278,221 NT 2,845 0 64,854 NT
5/6-11 239,717 0 6,579,046 NT 648 0 16,295 NT
Dose 3
12-15 352,881 § 9,759,909 NT 533 0 13,650 NT
16-17 215,316 0 5,884,863 NT 285 0 7,132 NT
6m-4/5 410,448 0 13,758,825 NT 277,773 § 10,024,797 NT
Dose 1 5/6-11 2,485,324 § 81,547,753 NT 1,469 0 49,843 NT
+ Dose
2 12-15 2,223,796 § 72,859,944 NS 1,410 0 48,910 NT
16-17 1,129,627 § 37,287,987 NT 1,216 0 40,559 NT
6m-4/5 221,610 0 6,325,107 NT 150,101 § 4,984,704 NT
5/6-11 1,334,839 § 34,943,578 NT 916 0 30,912 NT
Dose 1
12-15 1,179,935 § 29,750,039 NT 849 0 28,438 NT
Encephalitis or 16-17 607,886 § 15,734,035 NT 760 0 23,715 NT
Encephalomye
litis 6m-4/5 188,838 0 7,433,718 NT 127,672 § 5,040,093 NT
5/6-11 1,150,485 § 46,604,175 NT 553 0 18,931 NT
Dose 2
12-15 1,043,861 § 43,109,905 NS 561 0 20,472 NT
16-17 521,741 § 21,553,952 NT 456 0 16,844 NT
6m-4/5 96,950 0 3,945,744 NT 3,233 0 101,347 NT
5/6-11 259,110 § 10,548,412 NT 699 0 24,341 NT
Dose 3
12-15 370,652 0 15,282,789 NT 563 0 20,192 NT
16-17 229,634 0 9,331,463 NT 310 0 10,873 NT
Dose 1
Guillain-Barré + Dose 6m-4/5 352,025 0 11,830,401 NT 241,936 0 8,761,303 NT
Syndrome 2
Dose 1 6m-4/5 190,670 0 5,446,456 NT 131,384 0 4,374,485 NT

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 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
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Dose 2 6m-4/5 161,355 0 6,383,945 NT 110,552 0 4,386,818 NT

Dose 3 6m-4/5 83,022 0 3,391,294 NT 2,845 0 90,746 NT
Dose 1
+ Dose 6m-4/5 351,997 § 8,970,006 NT 241,927 0 6,548,151 NT
2
Hemorrhagic
Stroke Dose 1 6m-4/5 190,654 § 4,629,520 NT 131,379 0 3,567,371 NT
Dose 2 6m-4/5 161,343 0 4,340,486 NT 110,548 0 2,980,780 NT
Dose 3 6m-4/5 83,017 0 2,285,757 NT 2,845 0 66,970 NT
6m-4/5 351,972 § 12,028,216 NT 241,891 § 8,887,610 NS
Dose 1 5/6-11 2,215,661 23 72,925,239 NS 1,212 0 44,796 NT
+ Dose
2 12-15 2,038,029 25 66,706,657 NS 1,188 0 43,176 NT
16-17 1,044,876 15 34,462,183 NS 1,018 0 35,938 NT
6m-4/5 190,643 0 5,522,961 NT 131,361 § 4,424,088 NT
5/6-11 1,183,941 § 30,969,110 NS 755 0 27,077 NT
Dose 1
12-15 1,079,968 § 27,098,483 NS 704 0 24,320 NT
Immune 16-17 560,757 § 14,438,389 NS 635 0 20,921 NT
Thrombocytop
enia 6m-4/5 161,329 § 6,505,255 NT 110,530 § 4,463,522 NT
5/6-11 1,031,720 § 41,956,129 NS 457 0 17,719 NT
Dose 2
12-15 958,061 § 39,608,174 NS 484 0 18,856 NT
16-17 484,119 § 20,023,794 NS 383 0 15,017 NT
6m-4/5 83,012 0 3,415,558 NT 2,845 0 97,403 NT
5/6-11 239,675 0 9,830,404 NT 647 0 24,998 NT
Dose 3
12-15 352,826 0 14,573,683 NT 533 0 21,004 NT
16-17 215,255 § 8,769,474 NT 285 0 11,128 NT
6m-4/5 351,988 0 2,443,114 NT 241,924 0 1,679,814 NT
Dose 1 5/6-11 2,215,815 § 15,455,303 NS 1,212 0 8,392 NT
+ Dose
2 12-15 2,038,160 72 14,241,393 S 1,188 0 8,197 NT
16-17 1,044,928 56 7,299,458 S 1,018 0 7,014 NT
6m-4/5 190,650 0 1,323,939 NT 131,378 0 912,801 NT
5/6-11 1,184,019 § 8,261,973 NT 755 0 5,244 NT
Dose 1
12-15 1,080,046 § 7,547,573 NS 704 0 4,859 NT
Myocarditis/pe
ricarditis (All 16-17 560,782 § 3,917,140 NS 635 0 4,355 NT
settings) (1-7 6m-4/5 161,338 0 1,119,175 NT 110,546 0 767,013 NT
day)
5/6-11 1,031,796 § 7,193,330 NS 457 0 3,148 NT
Dose 2
12-15 958,114 § 6,693,820 S 484 0 3,338 NT
16-17 484,146 § 3,382,318 S 383 0 2,659 NT
6m-4/5 83,014 0 579,161 NT 2,845 0 19,413 NT
5/6-11 239,708 0 1,672,699 NT 648 0 4,517 NT
Dose 3
12-15 352,832 § 2,465,354 S 533 0 3,719 NT
16-17 215,272 13 1,497,801 S 285 0 1,990 NT
Myocarditis/pe 6m-4/5 351,988 § 7,252,205 NT 241,924 0 4,987,361 NT
ricarditis (All 5/6-11 2,215,815 12 45,978,229 NS 1,212 0 24,750 NT

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 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
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All rights reserved. No reuse allowed without permission.

Settings) (1-21 Dose 1 12-15 2,038,160 103 42,443,102 S 1,188 0 24,182 NT

day) + Dose
2 16-17 1,044,928 71 21,746,581 S 1,018 0 20,541 NT
6m-4/5 190,650 0 3,932,631 NT 131,378 0 2,711,909 NT
5/6-11 1,184,019 § 24,573,073 NT 755 0 15,431 NT
Dose 1
12-15 1,080,046 19 22,468,619 S 704 0 14,352 NT
16-17 560,782 16 11,655,098 S 635 0 12,742 NT
6m-4/5 161,338 § 3,319,574 NT 110,546 0 2,275,452 NT
5/6-11 1,031,796 § 21,405,156 NS 457 0 9,319 NT
Dose 2
12-15 958,114 84 19,974,483 S 484 0 9,830 NT
16-17 484,146 56 10,091,483 S 383 0 7,799 NT
6m-4/5 83,014 0 1,728,090 NT 2,845 0 54,542 NT
5/6-11 239,708 0 4,980,481 NT 648 0 13,186 NT
Dose 3
12-15 352,832 § 7,349,009 S 533 0 10,924 NT
16-17 215,272 14 4,436,604 S 285 0 5,871 NT
#
6m-4/5 352,019 0 2,427,241 NT 152,637 0 1,053,032 NT
Dose 1 5-6/11 #
2,215,967 § 15,450,396 NT 621 0 4,208 NT
+ Dose
2 12-15 2,038,335 55 14,242,747 S 1,188 0 8,114 NT
16-17 1,045,077 40 7,300,604 S 1,018 0 6,924 NT
#
6m-4/5 190,667 0 1,316,715 NT 82,934 0 573,125 NT
#
5-6/11 1,184,102 § 8,259,674 NT 398 0 2,691 NT
Dose 1
12-15 1,080,136 § 7,548,270 NT 704 0 4,819 NT
Myocarditis/pe
ricarditis 16-17 560,863 § 3,917,764 NS 635 0 4,297 NT
(IP/OP-ED) 6m-4/5 #
161,352 0 1,110,526 NT 69,703 0 479,907 NT
(1-7 day) #
5-6/11 1,031,865 § 7,190,722 NT 223 0 1,517 NT
Dose 2
12-15 958,199 § 6,694,477 S 484 0 3,295 NT
16-17 484,214 § 3,382,840 S 383 0 2,627 NT
#
6m-4/5 83,021 0 578,025 NT 1,185 0 7,882 NT
#
5-6/11 239,718 0 1,671,051 NT 352 0 2,405 NT
Dose 3
12-15 352,870 § 2,465,157 S 533 0 3,707 NT
16-17 215,311 § 1,498,007 S 285 0 1,966 NT
#
6m-4/5 352,019 0 7,198,601 NT 152,637 0 3,125,323 NT
Dose 1 5-6/11 #
2,215,967 § 45,959,404 NT 621 0 12,298 NT
+ Dose
2 12-15 2,038,335 61 42,446,709 S 1,188 0 23,893 NT
16-17 1,045,077 46 21,749,769 S 1,018 0 20,217 NT
Myocarditis/pe 6m-4/5 #
190,667 0 3,908,994 NT 82,934 0 1,702,556 NT
ricarditis
5-6/11# 1,184,102 § 24,564,532 NT 398 0 7,883 NT
(IP/OP-ED) Dose 1
(1-21 day) 12-15 1,080,136 § 22,470,533 NS 704 0 14,199 NT
16-17 560,863 12 11,656,804 S 635 0 12,513 NT
#
6m-4/5 161,352 0 3,289,607 NT 69,703 0 1,422,767 NT
#
Dose 2 5-6/11 1,031,865 § 21,394,872 NT 223 0 4,415 NT
12-15 958,199 § 19,976,176 S 484 0 9,694 NT

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 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
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All rights reserved. No reuse allowed without permission.

16-17 484,214 35 10,092,965 S 383 0 7,704 NT

#
6m-4/5 83,021 0 1,723,572 NT 1,185 0 22,367 NT
#
5-6/11 239,718 0 4,973,111 NT 352 0 6,892 NT
Dose 3
12-15 352,870 § 7,348,086 S 533 0 10,753 NT
16-17 215,311 § 4,437,033 S 285 0 5,721 NT
Dose 1 5/6-11 2,215,928 § 72,934,272 NS 1,212 0 44,796 NT
+ Dose 12-15 2,038,107 16 66,709,380 NS 1,188 0 43,176 NT
2 16-17 1,044,699 24 34,456,767 NS 1,017 0 35,896 NT
5/6-11 1,184,080 § 30,972,795 NT 755 0 27,077 NT
Dose 1 12-15 1,080,018 § 27,099,946 NS 704 0 24,320 NT
16-17 560,647 § 14,435,556 NT 635 0 20,921 NT
Narcolepsy
5/6-11 1,031,848 § 41,961,477 NS 457 0 17,719 NT
Dose 2 12-15 958,089 § 39,609,434 NS 484 0 18,856 NT
16-17 484,052 § 20,021,211 NS 382 0 14,975 NT
5/6-11 239,715 0 9,832,012 NT 648 0 25,021 NT
Dose 3 12-15 352,841 § 14,574,277 NS 533 0 21,004 NT
16-17 215,221 12 8,768,192 NS 285 0 11,128 NT
6m-4/5 352,009 0 8,942,566 NT 241,930 § 6,530,082 NT
Dose 1 5/6-11 2,215,960 § 55,955,653 NT 1,212 0 31,259 NT
+ Dose
2 12-15 2,038,354 0 51,165,669 NT 1,188 0 31,151 NT
16-17 1,045,115 § 26,327,584 NT 1,018 0 26,192 NT
6m-4/5 190,661 0 4,617,655 NT 131,381 § 3,559,300 NT
5/6-11 1,184,098 § 27,625,211 NT 755 0 19,695 NT
Dose 1
12-15 1,080,143 0 24,621,154 NT 704 0 18,574 NT
Non- 16-17 560,884 § 12,912,371 NT 635 0 16,176 NT
Hemorrhagic
Stroke 6m-4/5 161,348 0 4,324,911 NT 110,549 0 2,970,782 NT
5/6-11 1,031,862 0 28,330,442 NT 457 0 11,564 NT
Dose 2
12-15 958,211 0 26,544,515 NT 484 0 12,577 NT
16-17 484,231 § 13,415,213 NT 383 0 10,016 NT
6m-4/5 83,019 § 2,282,885 NT 2,845 0 66,156 NT
5/6-11 239,722 0 6,587,840 NT 648 0 16,549 NT
Dose 3
12-15 352,881 0 9,761,993 NT 533 0 13,822 NT
16-17 215,317 § 5,885,718 NT 285 0 7,299 NT
#
6m-4/5 239,532 0 6,178,317 NT 160,273 0 4,377,689 NT
Dose 1 5/6-11 2,215,976 0 56,012,340 NT 1,212 0 32,579 NT
+ Dose
2 12-15 2,038,334 § 51,168,510 NT 1,188 0 31,876 NT
Pulmonary 16-17 1,044,978 § 26,326,099 NS 1,018 0 27,082 NT
Embolism 6m-4/5 #
130,125 0 3,196,420 NT 87,477 0 2,391,693 NT
5/6-11 1,184,108 0 27,650,979 NT 755 0 20,295 NT
Dose 1
12-15 1,080,133 0 24,622,518 NT 704 0 18,935 NT
16-17 560,809 § 12,911,833 NS 635 0 16,775 NT

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 medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
All rights reserved. No reuse allowed without permission.

6m-4/5# 109,407 0 2,981,897 NT 72,796 0 1,985,996 NT

5/6-11 1,031,868 0 28,361,361 NT 457 0 12,284 NT
Dose 2
12-15 958,201 § 26,545,992 NT 484 0 12,941 NT
16-17 484,169 § 13,414,266 NT 383 0 10,307 NT
#
6m-4/5 55,239 0 1,527,770 NT 2,067 0 50,277 NT
5/6-11 239,722 § 6,610,019 NT 648 0 17,308 NT
Dose 3
12-15 352,879 0 9,766,897 NT 533 0 14,393 NT
16-17 215,293 § 5,886,669 NT 285 0 7,721 NT
6m-1 450,140 25 1,191,471 NS 302,275 15 872,958 NS
Dose 1 2-4/5 450,140 36 2,373,696 S 302,275 29 1,522,577 S
+ Dose 5/6-11 2,692,535 71 21,462,208 NS 1,667 0 13,078 NT
2 12-15 2,430,285 52 19,407,961 NS 1,545 0 12,180 NT
16-17 1,238,940 38 9,890,880 NS 1,300 0 10,220 NT
6m-1 245,400 14 660,359 NS 164,942 § 486,994 NS
2-4/5 245,400 21 1,284,771 S 164,942 § 821,447 NS
Dose 1 5/6-11 1,454,544 41 11,598,717 NS 1,051 0 8,240 NT
12-15 1,301,389 27 10,393,770 NS 947 0 7,458 NT
Seizures/Conv 16-17 671,951 24 5,363,845 NS 821 0 6,431 NT
ulsionsɸ 6m-1 204,740 11 531,112 NS 137,333 § 385,964 NS
2-4/5 204,740 15 1,088,925 S 137,333 § 701,130 S
Dose 2 5/6-11 1,237,991 30 9,863,491 NS 616 0 4,838 NT
12-15 1,128,896 25 9,014,191 NS 598 0 4,722 NT
16-17 566,989 16 4,527,035 NS 479 0 3,789 NT
6m-1 102,099 § 231,518 NT 3,376 § 8,115 NT
2-4/5 102,099 § 581,953 NS 3,376 0 18,177 NT
Dose 3 5/6-11 268,990 § 2,145,055 NS 725 0 5,768 NT
12-15 382,249 § 3,052,406 NS 587 0 4,684 NT
16-17 236,352 § 1,879,834 NS 318 0 2,532 NT
* Signal Status Definitions:
- NS: Test was initiated (cases > 3) but no signal was observed.
- S: Test met the statistical threshold for a signal.
- NT: Test did not initiate due to low outcome counts (cases <3).
§
Cell sizes 1-10 and cells that can be used to back-calculate small cell sizes were masked for confidentiality
† Common site thrombosis with thrombocytopenia is combined with unusual site thrombosis (broad) with

thrombocytopenia consisting of a thrombotic event (made up of other events such as acute myocardial infarction,
deep vein thrombosis etc.) and a thrombocytopenia event (defined in the IP, OP/PB setting). The overall setting
definition for the outcome depends on individual setting definitions for each of these components.
# For these outcome-age combinations, testing occurred in fewer than three data sources because one or more data
source did not have available background rates; for these outcome-age combinations, no. of doses are reported for
the data sources where sequential testing data was available.
ɸ For the outcome seizures/convulsions, the number of doses reported in both ages 6 months-1 year and 2-4/5 years

corresponds to the total number of doses monitored descriptively in ages 6 months-4/5 years; all other statistics from
sequential testing (number of outcomes, person-time, and signal status) are reported for the corresponding age
stratifications listed in the table above due to availability of background rates for those age strata.
Sequential testing ended earlier in ages 5/6-17 years due to limited accrual of new exposures; therefore, the data cuts
used are different from ages 6 months-4/5 years.

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medRxiv preprint doi: https://doi.org/10.1101/2023.10.13.23296903; this version posted October 15, 2023. The copyright holder for this preprint
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- Ages 5/6-17 years: Optum data through 4/2023, Carelon Research data through 1/2023, CVS Health data through
12/2022.
- Ages 6 months-4/5 years: Optum data through 1/2023, Carelon Research data through 3/2023, CVS Health data
through 2/2023

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