Available via license: CC BY-NC-ND 4.0
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mRNA COVID-19 vaccine safety among children and
adolescents: a Canadian National Vaccine Safety Network
cohort study
Phyumar Soe,
a
,
b
Otto G. Vanderkooi,
c
,
∗
Manish Sadarangani,
a
,
d
Monika Naus,
b
,
e
Matthew P. Muller,
f
James D. Kellner,
c
Karina A. Top,
g
,
m
Hubert Wong,
b
Jennifer E. Isenor,
g
Kimberly Marty,
a
Hennady P. Shulha,
a
,
d
Gaston De Serres,
h
,
i
Louis Valiquette,
j
Allison McGeer,
k
,
l
and
Julie A. Bettinger
a
,
d
,
∗∗
a
Vaccine Evaluation Center, BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
b
School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
c
Department of Pediatrics and Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
d
Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
e
BC Center for Disease Control, Vancouver, British Columbia, Canada
f
Department of Medicine, Unity Health Toronto, Toronto, Ontario, Canada
g
Canadian Center for Vaccinology, IWK Health and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
h
CHU de Québec-Université Laval, Québec City, Québec, Canada
i
Institut National de Santé Publique Du Québec, Québec City, Québec, Canada
j
Department of Microbiology and Infectious Diseases, Université de Sherbrooke, Sherbrooke, Quebec, Canada
k
Department of Microbiology, Sinai Health System, Toronto, Canada
l
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Summary
Background The Canadian National Vaccine Safety Network conducted active safety surveillance for COVID-19
vaccines. This study aimed to characterize the short-to-medium term safety of mRNA COVID-19 vaccines across
the pediatric age spectrum.
Methods In this cohort study, vaccinated and unvaccinated children and adolescents aged 6 months to 19 years from
eight Canadian provinces and territories were invited to participate. The outcome was a health event preventing daily
activities, resulting in school absenteeism, or requiring medical consultation. Age-stratified multivariable regression
models were used to examine health events associated with first and second doses of mRNA COVID-19 vaccines
across different age groups: children under 5, children aged 5–11 years and adolescents aged 12–19 years.
Findings From January 2021 through February 2023, a total of 259,361 individuals from the dose one survey, 131,032
from the dose 2 survey, and 1179 from the control survey were included. In the week following dose two, vaccinated
adolescents showed a higher proportion of health events [794 (4.6%) of 17,218 BNT162b2 recipients, 98 (8.5%) of 1153
mRNA-1273 recipients, 49 of (10.6%) of 464 heterologous schedule recipients] than unvaccinated adolescents [9 (3.7%) of
242controls],butmosteventswereself-limited and resolved within 7 days. No significant differences in proportion of
health events following mRNA COVID-19 vaccines were observed between vaccinated and unvaccinated groups
amongadolescentsafterdose1,oramongchildrenunder5orthoseaged5–11 years after any dose. Reported
myocarditis/pericarditis cases within 0–28 days peaked among male adolescents following dose 2, in three of (0.037%)
8088 homologous BNT162b2 recipients, and two of (0.529%) 378 homologous mRNA-1273 recipients.
Interpretation Our findings suggest that reported health events, including myocarditis/pericarditis, vary by pediatric
age group. Vaccinated adolescents reported health events more frequently following the second mRNA COVID-19
vaccine dose, while younger age groups did not report events more frequently than their unvaccinated counterparts.
Funding Canadian Immunization Research Network, Canadian Institutes of Health Research; Public Health Agency
of Canada; COVID-19 Immunity Task Force.
*Corresponding author. Department of Pediatrics and Alberta Children’s Hospital Research Institute, University of Calgary, Alberta Children’s
Hospital, 28 Oki Drive NW, Calgary AB T3B 6A8, Canada.
**Corresponding author. Department of Pediatrics, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia V5Z 4H4,
Canada.
E-mail addresses: Otto.vanderkooi@albertahealthservices.ca (O.G. Vanderkooi), jbettinger@bcchr.ubc.ca (J.A. Bettinger).
m
Current affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
The Lancet Regional
Health - Americas
2024;40: 100949
Published Online xxx
https://doi.org/10.
1016/j.lana.2024.
100949
www.thelancet.com Vol 40 December, 2024 1
Articles
Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Vaccine safety monitoring; Adverse events following immunization; Myocarditis/pericarditis
Introduction
In Canada, severe cases of SARS-CoV-2 infection among
children and adolescents have been reported since the
early stages of the pandemic.
1
Additionally, the potential
for severe post-infectious complications, including
multisystem inflammatory syndrome in children and
post-COVID syndrome (i.e., “long COVID”), have had
significant impact on these populations.
2
This un-
derscores the importance of vaccination for these
groups. Canadian COVID-19 vaccination programs in
these populations were introduced in a stepwise
manner: adolescents 12–17 years in May 2021; children
5–11 years in November 2021; and children 6 months-4
years in July 2022.
3
Canada primarily utilized two
mRNA vaccines in these age groups, BNT162b2 and
mRNA-1273, each with different authorized timing and
dosage regimens across various age groups.
3
The safety and efficacy of mRNA COVID-19 vaccines
in these populations were assessed in clinical trials and
post-marketing studies.
4–7
However, evidence is limited
from post-marketing studies that have examined
mRNA-COVID-19 vaccine safety in both older and
younger children including infants. A systematic review
and meta-analysis of COVID-19 vaccine safety among
individuals aged 3–17 years emphasized the urgent
need for multicenter, large-sample studies, particularly
in younger children and infants, with long-term follow-
up data.
8
Thus, evidence from large post-marketing
studies with longer follow-up data is required to pro-
vide a full understanding of mRNA COVID-19 safety
among pediatric populations.
The Canadian National Vaccine Safety (CANVAS)
network has been providing real-time vaccine safety
information to public health authorities in Canada since
2009.
9,10
The network has been active for COVID-19
vaccine safety since the COVID-19 vaccine rollout in
2020.
11
This study aimed to profile adverse events within
seven days and seven months following each mRNA
product and dose, and to evaluate the association be-
tween mRNA COVID-19 vaccination and health events
within seven days following vaccination in infants,
children and adolescents.
Methods
Study design and participants
This was a cohort study, and the safety surveillance in
the pediatric population used the same methodology as
Research in context
Evidence before this study
We searched the peer-reviewed (PubMed) and pre-print
(medRxiv) literature through September 4, 2024, focusing on
the safety of COVID-19 vaccines in infants, children and
adolescents. In addition to COVID-19 article filters from
PubMed, we included search terms “COVID-19”AND
“Vaccine”, AND “child* OR infant* OR adolescent*”AND
“safe* OR reactogenicity OR adverse event* OR tolerability OR
adverse events of special interest OR myocarditis OR
pericarditis.”We found several clinical and observational
studies that described adverse events after first and second
doses or booster doses of mRNA vaccines in children and
adolescents. Most studies focused on specific pediatric age
groups separately, including a few that reported adverse
events among children aged 5 years and above, and
adolescents. Some post-marketing studies, with vaccinated
children and adolescents reported adverse events but did not
conduct multivariable adjusted analyses to evaluate the health
event risk associated with specific COVID-19 vaccine products.
Another study included a broader age range of 6 months–17
years, and aimed to specifically detect rare outcomes or
adverse event of special interest. We found only one study
that examined vaccine-related serious adverse events over a
follow-up period of up to 14 months, but it did not include
children under 5 years of age.
Added value of this study
Findings from our cohort study contribute to a better
understanding of mRNA COVID-19 vaccine safety in the
youngest populations eligible for vaccination worldwide. Our
results offer valuable insights for clinicians, adolescents and
parents regarding what to expect following COVID-19
vaccination. These findings can be utilized to effectively
communicate with adolescents and parents about the risks
associated with COVID-19 infection and vaccination, thus
supporting them in making informed decisions.
Implications of all the available evidence
Our findings show mRNA COVID-19 vaccines are generally
safe and the risk of adverse events, including adverse events
of special interest, following mRNA COVID-19 vaccination
varies by pediatric age group and vaccine dose number. These
findings provide critical evidence to inform vaccination
policies in pediatric populations, in Canada and globally.
Continuous monitoring of vaccine safety, with separate
evaluations for children and adolescents, remains essential.
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2 www.thelancet.com Vol 40 December, 2024
in adults.
11
CANVAS employed a multi-pronged
recruitment strategy to engage a larger sample.
Vaccinated participants were recruited through auto-
invitation via the vaccine booking system and auto-
enrolment through vaccine registries. Additional
channels such as posters, information cards, and pam-
phlets at vaccination clinics were utilized, along with
promotion campaigns through local mass media and
social media platforms. For unvaccinated controls,
traditional methods were primarily used, including
distribution of posters, information cards, and pam-
phlets, complemented by media outreach and in-
vitations sent to previous CANVAS participants who had
consented to future contact. It is important to note that
not all provinces and territories employed all these
methods for both groups. Except for auto-enrolled par-
ticipants, all other interested participants were directed to
the CANVAS website for self-registration. Details of these
recruitment methods have been previously published.
12
From January 2021 through February 2023, we
enrolled participants aged 15–20 years or parents/
guardians of children 6 months to 14 years of age, with
an active email address and telephone number, who
were able to communicate in English or French, had
received a COVID-19 vaccine and resided in one of eight
Canadian provinces and territories (Alberta, British
Columbia, Nova Scotia, Ontario, Prince Edward Island,
Quebec, Yukon, Northwest Territories). Individuals
were able to participate as controls if they were unvac-
cinated and met the above inclusion criteria.
Study procedure
This was a retrospective analysis of data collected pro-
spectively. Unvaccinated participants completed one
online control survey, which captured health problems,
including events occurring within 7 days prior to the
survey and emergency department visits or hospitaliza-
tions in the previous six months. Vaccinated partici-
pants completed three online surveys: one each eight
days after the first and second doses, and one 7 months
after the first dose (Supplementary Fig. S1). The second
dose survey captured events experienced between dose
one and two surveys, and 7 days after dose two. All in-
dividuals completing the dose one survey were sent both
dose two and the 7-month follow-up survey irrespective
of dose two survey completion.
Our study protocol followed the earliest authorized
28-day interval between COVID-19 doses,
13
and the
follow-up survey for vaccinated individuals was sched-
uled to be sent six months after the second dose,
aligning with the six-month observational period for the
unvaccinated groups. However, due to challenges in
vaccine supply and distribution across Canada, subse-
quent public health recommendation extended the in-
terval between dose one and dose two,
14
and participants
were not provided the second dose survey in a stan-
dardize way. As a result, the follow-up survey was
administered seven months after the first dose to ensure
standardized follow-up of the vaccinated cohort at an
interval close to the unvaccinated group’s follow-up.
Additionally, this allowed inclusion of all participants,
irrespective of the receipt or timing of a second dose.
This follow-up survey only examined whether vaccinated
participants visited an emergency department or were
hospitalized during the 7-month follow-up period.
The survey captured demographic data (age group,
sex assigned at birth, ethnicity), general health status,
pregnancy and lactation status, previous SARS-CoV-2
infection, vaccine product, occurrence or worsening of
health events among controls or events following im-
munization. For adolescents, the ethnicity question was
only included in the dose two survey. Participants who
reported medically attended health events received a
follow-up call for more details. We used Medical Dic-
tionary for Regulatory Activities terminology (MedDRA)
to code diagnoses from surveys and phone follow-ups.
Research Ethics Board approval was obtained at all
sites (British Columbia and Yukon: University of British
Columbia Children’s & Women’s, Ref: H20-03704;
Quebec: Centre Intégré univrsitaire de santé et de ser-
vices sociaux de l’Estrie, Ref: MP-31-2021-4044; Nova
Scotia and Prince Edward Island: Health Prince Edward
Island and IWK Health Research, Ref: 1026400; Alberta:
Conjoint Health REB, University of Calgary, Ref:
REB20-2177; Ontario: Unity Health Toronto, Ref:
20–334). All participants, or parents/guardians, pro-
vided informed consent electronically.
Vaccine delivery and outcomes
For this analysis, we included vaccinated children and
adolescents who received BNT162b2 or mRNA-1273
and were not pregnant or breastfeeding at time of sur-
vey completion. The authorized doses of BNT162b2
were 30 μg for adolescents, 10 μg for those aged 5–11
years, and 3 μg for children under 5 years of age. For
mRNA-1273, the authorized doses were 100 μg for ad-
olescents, 50 μg for those aged 6–11 years, and 25 μg for
children under 6 years.
3
We included unvaccinated in-
dividuals who were not pregnant or breastfeeding at the
time of survey completion. The COVID-19 vaccine
product for each dose was collected either by electronic
transfer from the vaccination registry or entered by the
participants from their vaccine records. For dose two,
three different vaccine groups were evaluated: homolo-
gous BNT162b2, homologous mRNA-123, and heterol-
ogous (mixed) vaccine regimens. The outcome variable
was a composite outcome, defined as a new health event
or worsening of a pre-existing condition sufficient to
cause school absenteeism, require a medical consulta-
tion and/or prevent daily activities in the previous 7 days
(for controls) or within 7 days following vaccination for
vaccinated individuals.
We examined two adverse events of special interest
(myocarditis/pericarditis and anaphylaxis) within 7 days
Articles
www.thelancet.com Vol 40 December, 2024 3
following first and second doses, as well as during the
interval between the doses, and over the 7-month period
following dose one. These analyses followed the Brighton
Collaboration guidelines for adverse events of special in-
terest case definitions and reporting.
15,16
Individuals with
self-reported diagnoses of myocarditis/pericarditis/
anaphylaxis from inpatient or outpatient hospital care were
defined as cases. Since CANVAS relied on participant-
based reporting, medical chart review was not done and
the results of laboratory and imaging studies were not
available. Therefore, myocarditis/pericarditis or anaphy-
laxis diagnoses were at Brighton Collaboration level 4
certainty (insufficient evidence to meet levels 1–3, where
key data are ‘unknown’or ‘unobtainable’).
15,16
Statistical analysis
We estimated age specific proportions of health events,
including events requiring emergency department visit
or hospitalization, injection site reactions (vaccinated
group only), common and uncommon specific symp-
toms, onset and duration of health events within 7 days
following vaccination by vaccine exposure and dose, or
prior 7 days for controls. The frequency of reported
health events was classified as common (<1/10 to ≥1/
100), uncommon (<1/100 to ≥1/1000), rare (<1/1000 to
≥1/10,000), and very rare (<1/10,000) as specified by
European Medicines Agency.
17
Further, we assessed
health events requiring emergency department visit or
hospitalization within 7-months following dose one or
prior six months for controls. We also examined infor-
mation on participants’characteristics, medical consul-
tation, and level of care received for those with
myocarditis, pericarditis, and anaphylaxis.
To examine the association between vaccine expo-
sure and health events within 7 days following vacci-
nation, age-stratified multivariable generalized linear
regression models with a log link were built for each
vaccine product and dose. The estimated relative risk
(RR) and 95% confidence intervals (CIs) were reported.
In the multivariable models, we adjusted for potential
confounders and risk factors, including sex assigned at
birth (male or female), health status (five-level categor-
ical variable: excellent, very good, good, fair/poor, or
unknown), province, and previous COVID-19 infection
(yes or no). We did complete case analysis as no variable
had more than 5% missing data. Since the reported
health status could have been affected by vaccination in
the vaccinated group, we conducted sensitivity analyses
by fitting multivariable models without the health status
variable. Data cleaning was done in SAS version 9.4
(SAS Institute) and analysis was completed in R soft-
ware version 4.1.1 (R foundation for Statistical
Computing, Vienna, Austria).
Role of funding source
The funder of the study had no role in study design,
data collection, data analysis, data interpretation, or
writing of the report. The corresponding authors had
full access to the data in the study and had final
responsibility for the decision to submit for
publication.
Results
Overall survey completion among enrolled participants
was 23% for unvaccinated controls and 47% for vacci-
nated participants in the Dose 1 survey. A total of
259,361 and 131,032 children and adolescents were
included in the dose 1 and 2 analyses, respectively
(Fig. 1). Most children aged 5–11 years and adolescents
aged 12–19 years received the BNT162b2 vaccine for
their first and second doses, whereas most children
under 5 years received the mRNA-1273 vaccine for both
doses. Less than 10% of vaccinated individuals in each
pediatric age group received a heterologous series. A
total of 1179 participants were included in the control
sample (Fig. 2).
Risk of health events
Vaccinated and control participants’characteristics and
vaccine products are shown in Table 1 for dose one and
Supplementary Table S1 for dose two. Most vaccine
recipients were children aged 5–11 years of age and
reported excellent/very good/good health (≥90%). In the
week following dose one, the occurrence of a health
event severe enough to prevent daily activities, result in
school absenteeism, or require a medical consultation
among vaccinated individuals, regardless of age group,
was similar or lower than in controls except mRNA-1273
recipients aged 5–11 years (Table 2). In the multivariable
analysis, adjusting for sex, health status, province, and
previous SARS-CoV-2 infection, mRNA COVID-19 vac-
cines were not associated with an increased risk of
health events in all age groups within 7 days following
dose one (Fig. 3).
In the week following dose two, the proportion of
health events were generally higher than after dose 1
(Table 2). For children (6 months-4 years and 5–11
years), the incidence of health events after dose two was
not significantly higher than controls, and there was no
association between health events and either mRNA
COVID-19 vaccine product (Fig. 3). Among the children
aged 5–11 years, only three received homologous
mRNA-1273, with one reporting a health event within 7
days following vaccination. Due to the limited sample
size, regression analyses were not performed for this
group. However, adolescents reported more health
events after dose 2 and this significant increase in health
events was observed with both mRNA vaccines and
heterologous regimes (Fig. 3). In the sensitivity analysis,
multivariable models that did not adjust for the health
status variable produced estimates similar to those in
the main analysis for all vaccine products and doses
(Supplementary Table S2).
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4 www.thelancet.com Vol 40 December, 2024
In the week following doses 1 and 2, the proportion
of health events requiring an emergency department
visit or hospitalization among vaccinated individuals
ranged from 0% to 0.9%. No hospitalizations were re-
ported among unvaccinated children and adolescents
(Table 2).
Injection-site reactions and specific symptoms:
reportedwithin7daysafterdoses1and2
Tables 2–4present the occurrence of local reactions, and
other reported specific symptoms following the first and
second doses of mRNA COVID-19 vaccines compared
with controls. The proportion of individuals with local
reaction was highest among vaccinated adolescents
(61.3–77.8%), followed by vaccinated children aged 5–11
years (48.2–62.2%) and children under 5 years of age
(19.2–31.9%). By comparing vaccine product, injection
site reactions occurred more frequently among mRNA-
1273 recipients than BNT162b2 recipients (Table 2).
Commonly reported systemic symptoms included
feeling unwell, fever, vomiting or diarrhea, cough,
headache, sore throat, and rhinorrhea. Vaccinated
Unvaccinated
1180 completed survey
1 pregnant adolescent
1179
Under 5 years: 502
5-11 years: 435
12-19 years: 242
Fig. 2: Analytic sample for unvaccinated children and adolescents
(aged 6 Months to 19 Years).
Exclude 9 pregnant
and 4 breaseeding
adolescents
127301 did not
complete Dose 2
survey, 1016 unknown
vaccine dose 2
product, 4 ChAdOx1-S,
8 pregnant adolescents
Follow-up*
19
Follow-up*
1433
Follow-up*
120490
60 unknown vaccine product, 36 ChAdOx1-S
recipients, 43 pregnant/ breaseeding adolescents
Vaccinated
259,500 completed Dose one survey
BNT162b2 (246229)
Follow-up*
124
<5yrs
234
5-11yrs
206197
12-19yrs
39798
Dose two
77
Dose two
109896
Dose two
17579
<5yrs
9056
5-11yrs
37
12-19yrs
4039
Dose two
2212
Dose two
12
Dose two
1256
mRNA-1273 (13132)
Follow-up*
18649
Follow-up*
5042
Fig. 1: Analytic sample for vaccinated children and adolescents (aged 6 months to 19 years). The participants in Dose two included individuals
who received both homologous and heterologous (mixed) vaccine regimens. *Dose 1 vaccine product presented. The number of participants
refers to those who completed three surveys (Dose 1, Dose 2, and the 7-month follow-up), as well as those who completed only the Dose 1 and
7-month follow-up surveys but not the Dose 2 survey.
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www.thelancet.com Vol 40 December, 2024 5
adolescents reported these symptoms more frequently
than vaccinated children did in the week following dose
two. Other symptoms were uncommon and occurred in
similar proportions across vaccinated and unvaccinated
groups (Tables 3 and 4). Among vaccine recipients,
around 65–80% of adolescents with health events
experienced onset within 1–24 h of vaccination, whereas
about 67–86% of younger age groups had onset of
health events within 3 days after vaccination (Fig. 4).
Most symptoms resolved within the 7 days after vacci-
nation (Fig. 5), regardless of vaccine product, dose or
age group.
7-Month information on emergency visits or
hospitalization
Follow-up information was available for 56% of all
vaccinated individuals 7 months after dose one, while
87% of unvaccinated controls responded to the ques-
tions regarding emergency department visits/hospitali-
zations in the previous 6 months. Overall, children
under 5 years of age reported visiting the emergency
department more often than older children or adoles-
cents (Table 2). Among respondents, the proportion of
hospitalizations in both vaccinated and unvaccinated
individuals varied between 0% and 0.8%. Of those who
Children (6 months–4 years) Children (5–11 years) Adolescent (12–19yrs)
Controls
N = 502
BNT162b2
N = 234
mRNA-
1273 N = 9056
Controls
N = 435
BNT162b2
N = 206,197
mRNA-
1273 N = 37
Controls
N = 242
BNT162b2
N = 39,798
mRNA-1273
N = 4039
Median age in years (Interquartile range) 2 (1–4) 2 (1–3) 2 (1–3) 7 (6–9) 8 (6–10) 9 (6–11) NA NA NA
Sex assigned at birth
Male 284 (56.6%) 119 (51%) 4705 (52%) 234 (53.8%) 105,643 (51.2%) 17 (45.9%) 124 (51.2%) 18,552 (46.6%) 1485 (36.8%)
Female 218 (43.4%) 115 (49%) 4338 (47.9%) 201 (46.2%) 100,316 (48.7%) 19 (51.4%) 118 (48.8%) 21,111 (53%) 2542 (62.9%)
Other
a
0 (0%) 0 (0%) 0 (0%) 0 (0%) 224 (0.1%) 0 (0%) 0 (0%) 130 (0.3%) 1 (<0.1%)
Decline 0 (0%) 0 (0%) 13 (0.1%) 0 (0%) 14 (<0.1%) 1 (2.7%) 0 (0%) 5 (<0.1%) 12 (0.3%)
Province
Alberta 63 (12.5%) 30 (12.8%) 480 (5.3%) 96 (22.1%) 3125 (1.5%) 2 (5.4%) 75 (31%) 4766 (12%) 376 (9.3%)
BC/Yukon/NWT 296 (59%) 15 (6.4%) 5343 (59%) 173 (39.8%) 64,747 (31.4%) 20 (54.1%) 65 (26.9%) 10,502 (26.4%) 1042 (25.8%)
Nova Scotia/PE 9 (1.8%) 2 (0.9%) 118 (1.3%) 4 (0.9%) 196 (0.1%) 0 (0%) 11 (4.5%) 394 (1%) 27 (0.7%)
Ontario 134 (26.7%) 37 (15.8%) 308 (3.4%) 156 (35.9%) 1231 (0.6%) 5 (13.5%) 87 (36%) 3595 (9%) 291 (7.2%)
Quebec 0 (0%) 150 (64.1%) 2807 (31%) 6 (1.4%) 136,898 (66.4%) 10 (27%) 4 (1.7%) 20,541 (51.6%) 2303 (57%)
Health status
Excellent 341 (67.9%) 156 (67%) 5894 (65.1%) 269 (61.8%) 114,738 (55.6%) 16 (43.2%) 96 (39.7%) 13,713 (34.5%) 944 (23.4%)
Very good 119 (23.7%) 68 (29%) 2648 (29.2%) 142 (32.6%) 76,042 (36.9%) 16 (43.2%) 87 (36%) 15,763 (39.6%) 1608 (39.8%)
Good 35 (7.0%) 10 (4.3%) 443 (4.9%) 21 (4.8%) 13,399 (6.5%) 4 (10.8%) 49 (20.2%) 7901 (19.9%) 1155 (28.6%)
Fair or poor 6 (1.2%) 0 (0%) 39 (0.4%) 3 (0.7%) 1337 (0.6%) 0 (0%) 9 (3.7%) 792 (2%) 138 (3.4%)
Unknown 1 (0.2%) 0 (0%) 32 (0.4%) 0 (0%) 681 (0.3%) 1 (2.7%) 1 (0.4%) 1629 (4.1%) 194 (4.8%)
Race and ethnicity
Black 1 (0.2%) 3 (1.3%) 44 (0.5%) 4 (0.9%) 2770 (1.3%) 0 (0%) NA NA NA
White 346 (68.9%) 158 (67.5%) 5838 (64.5%) 301 (69.2%) 140,645 (68.2%) 15 (40.5%) NA NA NA
Indigenous 6 (1.2%) 2 (0.9%) 118 (1.3%) 10 (2.3%) 2521 (1.2%) 2 (5.4%) NA NA NA
Latino 3 (0.6%) 6 (2.6%) 171 (1.9%) 5 (1.1%) 3706 (1.8%) 0 (0%) NA NA NA
Middle Eastern 3 (0.6%) 4 (1.7%) 104 (1.1%) 8 (1.8%) 3315 (1.6%) 0 (0%) NA NA NA
Mixed 80 (15.9%) 29 (12.4%) 1202 (13.3%) 56 (12.9%) 13,224 (6.4%) 3 (8.1%) NA NA NA
East Asian 24 (4.8%) 10 (4.3%) 682 (7.5%) 9 (2.1%) 10,576 (5.1%) 2 (5.4%) NA NA NA
South Asian 9 (1.8%) 7 (3.0%) 277 (3.1%) 8 (1.8%) 4896 (2.4%) 1 (2.7%) NA NA NA
Southeast Asian 6 (1.2%) 4 (1.7%) 216 (2.4%) 3 (0.7%) 4027 (2%) 0 (0%) NA NA NA
Other 10 (2.0%) 7 (3.0%) 181 (2.0%) 5 (1.1%) 7626 (3.7%) 0 (0%) NA NA NA
Unknown/Decline 14 (2.8%) 4 (1.7%) 223 (2.5%) 26 (5.9%) 12,891 (6.2%) 14 (37.8%) NA NA NA
Previous SARS-COV-2 infection
Yes 144 (28.2%) 83 (35.5%) 3711 (40.9%) 147 (33.8%) 11,723 (5.7%) 5 (13.5%) 47 (19.4%) 2622 (6.6%) 233 (5.8%)
Immunocompromised
Yes 4 (0.8%) 0 (0%) 15 (0.2%) 4 (0.9%) 630 (0.3%) 1 (2.7%) 3 (1.2%) 338 (0.8%) 54 (1.3%)
Autoimmune condition
Yes 3 (0.6%) 1 (0.4%) 29 (0.3%) 9 (2.1%) 1379 (0.7%) 1 (2.7%) 5 (2.1%) 583 (1.5%) 99 (2.5%)
Data are n (%).
a
Intersex or other, UK: Unknown, BC/YK/NWT: British Columbia, Yukon, Northwest Territories, PE: Prince Edward Island, NA: Age information for adolescents was collected only in
categorical format. The question regarding ethnicity among adolescents was only in Dose 2 survey.
Table 1: Participants’characteristics: Unvaccinated and vaccinated individuals by product (dose 1).
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6 www.thelancet.com Vol 40 December, 2024
visited the emergency department or were hospitalized
in the follow-up period or in the prior 6 months, the
median number of visits was 1, with an interquartile
range of 1 to 1 in both vaccinated and unvaccinated
groups.
Myocarditis/pericarditis
Following dose one, eight individuals (children aged
5–11 years: two [0.001%] of 206,197 BNT162b2 re-
cipients; adolescents: six [0.015%] of 39,798 BNT162b2
recipients), received a physician diagnosis of myocar-
ditis or pericarditis within 0–28 days after BNT162b2
(Supplementary Table S3). Among these cases, two were
diagnosed with pericarditis, one with perimyocarditis,
and the remaining five with myocarditis. Symptoms
such as chest tightness, palpitations occurred within
24–120 h after vaccination in four cases. Four of the
eight cases were hospitalized, with one male adolescent
in the intensive care unit for one day. Symptoms
resolved within 7 days of onset for four individuals,
while they persisted for more than 7 days in the
remaining cases.
Following dose two a myocarditis or pericarditis
diagnosis within 0–28 days was reported for nine new
cases (children 5–11years: two [0.002%] of 109,674
BNT162b2 recipients, adolescents: four [0.023%]of
17,218 BNT162b2 recipients, three [0.185%] of 1617
mRNA-1273 recipients including one heterologous
series recipient) (Supplementary Table S3). Of nine
cases, only two cases were diagnosed with pericar-
ditis, and the remaining seven with myocarditis. The
highest incidence occurred among males aged 12–19
years old following dose 2, with three (0.037%) of
8088 BNT162b2 recipients, and two (0.529%) of 378
mRNA-1273 recipients. For male adolescents, the
incidence after the second dose of homologous
BNT162b2 was significantly lower than that of ho-
mologous mRNA-1273. Five of the nine cases pre-
sented with symptoms such as chest tightness and/or
palpitation within 3 days of vaccination. Four of the
nine cases were hospitalized, with one male adoles-
cent in intensive care unit for 4 days. Four of the nine
caseshadtheirsymptomsresolvewithin7daysof
vaccination while symptoms persisted for more than 7
days in the rest.
Of the 140,591 vaccinated adolescents and children
aged 5–11 years in the 7-month follow-up survey, twelve
(0.008%) new diagnoses of myocarditis or pericarditis
were reported (Supplementary Table S3). These in-
dividuals visited the emergency department or were
hospitalized a mean of 143 days (median 142 days) after
receiving dose one (range 82–210 days), and 94 days
(median 83 days) after receiving dose two (range 42–166
days). No cases of myocarditis or pericarditis were
detected in vaccinated children under 5 years of age or
in the control group.
Children (6 months–4 years) Children (5–11 years) Adolescent (12–19yrs)
Control BNT162b2 mRNA-1273 Mixed Control BNT162b2 mRNA-1273 Mixed Control BNT162b2 mRNA-1273 Mixed
Within 7 days following Dose 1 or previous 7 days (controls)
Total N = 502 N = 234 N = 9056 N = 435 N = 206,197 N = 37 N = 242 N = 39,798 N = 4039
Injection site reactions
a
NA 45 (19.2%) 2079 (22.9%) NA 99,428 (48.2%) 23 (62.2%) NA 24,402 (61.3%) 2995 (74.1%)
Health event
b
68 (13.5%) 15 (6.4%) 862 (9.5%) 38 (8.8%) 8072 (3.9%) 6 (16.2%) 9 (3.7%) 1436 (3.6%) 162 (4%)
Consulted HCP 16 (3.2%) 7 (3%) 197 (2.2%) 6 (1.4%) 1291 (0.6%) 2 (5.4%) 2 (0.8%) 263 (0.7%) 34 (0.8%)
ED visit 4 (0.8%) 0 (0%) 48 (0.53%) 0 (0%) 301 (0.15%) 0 (0%) 0 (0%) 89 (0.22%) 13 (0.3%)
Hospitalization 0 (0%) 0 (0%) 4 (0.04%) 0 (0%) 26 (0.01%) 0 (0%) 0 (0%) 10 (0.03%) 1 (0.02%)
Within 7 days following Dose 2 or previous 7 days (controls)
Total N = 502 N = 70 N = 2015 N = 204 N = 435 N = 109,674 N = 3 N = 231 N = 242 N = 17,218 N = 1153 N = 464
Injection site reactions
a
NA 16 (22.9%) 641 (31.9%) 60 (29.4%) NA 64,963 (59.2%) 1 (33.3%) 131 (56.7%) NA 11,351 (65.9%) 881 (76.4%) 361 (77.8%)
Health event
b
68 (13.5%) 7 (10%) 173 (8.6%) 19 (9.3%) 38 (8.8%) 3420 (3.1%) 1 (33.3%) 10 (4.3%) 9 (3.7%) 794 (4.6%) 98 (8.5%) 49 (10.6%)
Consulted HCP 16 (3.2%) 3 (4.3%) 37 (1.8%) 4 (2%) 6 (1.4%) 333 (0.3%) 1 (33.3%) 2 (0.9%) 2 (0.8%) 95 (0.6%) 12 (1.0%) 7 (1.5%)
ED visit 4 (0.8%) 0 (0%) 11 (0.5%) 1 (0.5%) 0 (0%) 94 (0.09%) 1 (33.3%) 2 (0.9%) 0 (0%) 42 (0.24%) 3 (0.26%) 4 (0.86%)
Hospitalization 0 (0%) 0 (0%) 0 (0%) 1 (0.5%) 0 (0%) 9 (0.01%) 0 (0%) 0 (0%) 0 (0%) 5 (0.03%) 3 (0.26%) 0 (0%)
7 months following Dose 1 or previous 6 months among controls
c
Total N = 495 N = 124 N = 5042 N = 420 N = 120,490 N = 19 N = 109 N = 18,649 N = 1433
ED visit 65 (13.1%) 4 (3.2%) 347 (6.9%) 26 (6.2%) 3047 (2.5%) 1 (5.3%) 7 (6.4%) 411 (2.2%) 43 (3.0%)
Hospitalization 2 (0.4%) 0 (0%) 41 (0.81%) 1 (0.24%) 300 (0.25%) 0 (0%) 1 (0.92%) 45 (0.24%) 5 (0.35%)
Data are n(%) HCP: health care providers ED visit: Emergency department visit NA: Not available.
a
All participants were asked about injection site reactions (Redness, pain or swelling at injection site/above and
below in the immunized arm).
b
Health event severe enough to result in prevention of daily activities, school absenteeism, or requiring medical consultation.
c
Dose 1 vaccine product presented. The same control
groups were used for both doses 1 and 2.
Table 2: Self-reported injection site reaction and health events among unvaccinated (previous 7 days, last 6 months) and vaccinated groups (within 7 days after doses 1 and 2, 7
months after dose 1).
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Fig. 3: Relative risk of health events within 7 days following vaccination, by vaccine product and dose, between children and adolescents,
compared to unvaccinated controls. The graph represents three age groups: children (6 months–4 years), (5–11 years), and adolescents (12–19
years). Outcome: health event severe enough to result in prevention of daily activities, school absenteeism, or requiring medical consultation.
Blue triangles and red circles represent adjusted Relative risk (RR) for vaccine dose 1 and 2, with 95% confidence interval (95% CIs). The
reference groups are unvaccinated participants in the same age group. RRs are adjusted for sex assigned at birth, health status, province, and
previous SARS-CoV-2 infection. The x-axis of each graph is a log-scale. Since only 3 children aged 5–11 years received homologous mRNA-1273,
regression analyses were not performed for this group.
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Anaphylaxis
In the week following dose one, six adolescents (five
[0.002%] of 246,229 BNT162b2 recipients, one [0.008%]
of 13,132 mRNA-1273 recipients) were diagnosed with
anaphylaxis. All of them were female and presented
with urticarial rash, with or without swelling of the
throat/face, chest tightness, and difficulty breathing.
Half developed symptoms within 24 h (two within
60 min, one within 24 h), but all resolved within 7 days
without requiring hospitalization. In the week following
dose two, one adolescent female reported “anaphylactic
reaction”within 24 h after receiving a mixed schedule
and symptoms resolved on the day of onset.
No cases of anaphylaxis were reported within 7 days
following dose 1 and 2 among vaccinated children, nor
in the unvaccinated controls.
Discussion
Findings from our cohort study provide reassuring
real-world evidence of the safety of mRNA COVID-19
vaccines (BNT162b2, mRNA-1273, mixed schedules)
in children and adolescents while also confirming
some known risks. The occurrence of health events
among children and adolescents within 7 days
following the first dose of an mRNA-COVID vaccine
Children (6 months–4 years) Children (5–11 years) Adolescent (12–19yrs)
Controls
N = 502
BNT162b2
N = 234
mRNA-1273
N = 9056
Controls
N = 435
BNT162b2
N = 206,197
mRNA-1273
N=37
Controls
N = 242
BNT162b2
N = 39,798
mRNA-
1273
N = 4039
Injection site reactions reported with health events
a
NA 6 (2.6%) 263 (2.9%) NA 4768 (2.3%) 5 (13.5%) NA 1110 (2.8%) 140 (3.5%)
General symptoms
Unwell
b
39 (7.8%) 10 (4.3%) 609 (6.7%) 29 (6.7%) 5343 (2.6%) 5 (13.5%) 6 (2.5%) 1175 (3%) 148 (3.7%)
Fever (≥38▫C) 35 (7%) 13 (5.6%) 530 (5.9%) 20 (4.6%) 2869 (1.4%) 3 (8.1%) 2 (0.8%) 386 (1%) 59 (1.5%)
Febrile convulsion 0 (0%) 0 (0%) 4 (0.1%) 0 (0%) 3 (<0.1%) 0 (0%) 0 (0%) 3 (0%) 0 (0%)
GI symptoms
c
31 (6.2%) 5 (2.1%) 291 (3.2%) 10 (2.3%) 3080 (1.5%) 3 (8.1%) 3 (1.2%) 610 (1.5%) 87 (2.2%)
Joint pain/stiffness 1 (0.2%) 1 (0.4%) 17 (0.2%) 2 (0.5%) 433 (0.2%) 2 (5.4%) 0 (0%) 291 (0.7%) 56 (1.4%)
Earache/ear pain/ear symptoms 3 (0.6%) 3 (1.3%) 66 (0.7%) 3 (0.7%) 421 (0.2%) 0 (0%) 0 (0%) 97 (0.2%) 18 (0.4%)
Nasal congestion/sinus congestion 42 (8.4%) 3 (1.3%) 436 (4.8%) 14 (3.2%) 2908 (1.4%) 4 (10.8%) 3 (1.2%) 373 (0.9%) 38 (0.9%)
Runny nose 48 (9.6%) 6 (2.6%) 523 (5.8%) 13 (3%) 2809 (1.4%) 2 (5.4%) 2 (0.8%) 326 (0.8%) 40 (1%)
Sore throat 18 (3.6%) 2 (0.9%) 178 (2%) 13 (3%) 2956 (1.4%) 3 (8.1%) 4 (1.7%) 440 (1.1%) 48 (1.2%)
Neurologic symptoms
Headache or migraine 10 (2%) 2 (0.9%) 126 (1.4%) 11 (2.5%) 3722 (1.8%) 5 (13.5%) 5 (2.1%) 924 (2.3%) 118 (2.9%)
Dizziness/light-headedness 1 (0.2%) 0 (0%) 7 (0.1%) 2 (0.5%) 486 (0.2%) 0 (0%) 1 (0.4%) 369 (0.9%) 54 (1.3%)
Fainting 0 (0%) 0 (0%) 1 (<0.1%) 0 (0%) 52 (<0.1%) 0 (0%) 0 (0%) 56 (0.1%) 4 (0.1%)
Loss of taste/smell 0 (0%) 0 (0%) 12 (0.1%) 2 (0.5%) 147 (0.1%) 0 (0%) 1 (0.4%) 67 (0.2%) 4 (0.1%)
Paresthesia 0 (0%) 0 (0%) 0 (0%) 1 (0.2%) 72 (<0.1%) 0 (0%) 1 (0.4%) 87 (0.2%) 21 (0.5%)
Seizure or convulsion 0 (0%) 0 (0%) 4 (<0.1%) 0 (0%) 14 (<0.1%) 0 (0%) 0 (0%) 16 (<0.1%) 1 (<0.1%)
Other neurologic symptoms
d
0 (0%) 0 (0%) 5 (0.1%) 0 (0%) 52 (<0.1%) 0 (0%) 0 (0%) 42 (0.1%) 10 (0.2%)
Coagulation symptoms
Symptoms of blood clot/bleeding
e
0 (0%) 0 (0%) 2 (<0.1%) 0 (0%) 30 (<0.1%) 0 (0%) 0 (0%) 21 (0.1%) 3 (0.1%)
Bruising or pinpoint dark red rash
f
0 (0%) 0 (0%) 7 (0.1%) 0 (0%) 44 (<0.1%) 0 (0%) 0 (0%) 18 (<0.1%) 4 (0.1%)
Allergic-like
Rash or hives 4 (0.8%) 0 (0%) 69 (0.8%) 3 (0.7%) 334 (0.2%) 0 (0%) 0 (0%) 70 (0.2%) 19 (0.5%)
Itchy or painful eyes 2 (0.4%) 1 (0.4%) 52 (0.6%) 2 (0.5%) 388 (0.2%) 2 (5.4%) 0 (0%) 157 (0.4%) 29 (0.7%)
Tearing or eye discharge 6 (1.2%) 1 (0.4%) 116 (1.3%) 1 (0.2%) 287 (0.1%) 0 (0%) 0 (0%) 77 (0.2%) 12 (0.3%)
Swelling of the throat/tongue 0 (0%) 0 (0%) 17 (0.2%) 0 (0%) 114 (0.1%) 1 (2.7%) 1 (0.4%) 84 (0.2%) 9 (0.2%)
Cardiorespiratory
Chest tightness/discomfort/pain 0 (0%) 0 (0%) 21 (0.2%) 0 (0%) 272 (0.1%) 1 (2.7%) 2 (0.8%) 218 (0.5%) 29 (0.7%)
Rapid heart rate/palpitations 1 (0.2%) 0 (0%) 19 (0.2%) 0 (0%) 183 (0.1%) 0 (0%) 2 (0.8%) 139 (0.3%) 22 (0.5%)
Cough 47 (9.4%) 4 (1.7%) 475 (5.2%) 20 (4.6%) 3038 (1.5%) 2 (5.4%) 3 (1.2%) 294 (0.7%) 37 (0.9%)
Difficulty breathing 1 (0.2%) 2 (0.9%) 66 (0.7%) 2 (0.5%) 313 (0.2%) 1 (2.7%) 0 (0%) 181 (0.5%) 24 (0.6%)
Data are n(%).
a
Participants who reported both injection site reaction and health events severe enough to result in prevention of daily activities, school absenteeism, or requiring medical consultation. Only
those who indicated a health event were asked to provide details of their symptoms. As symptoms are not mutually excluded, participants can report more than one symptoms.
b
Tiredness, weakness,
muscle aches, fatigue, or chills.
c
GI symptoms: Gastrointestinal symptoms such as nausea, vomiting, diarrhea, or stomach pain.
d
Weakness or paralysis of the arms or legs, confusion, change in personality
or behavior, or difficulty with urination or defecation.
e
Symptoms of blood clot or bleeding, including swelling, pain in legs, or bruising or pinpoint dark rash; GI symptoms: nausea, vomiting, diarrhea, or
stomach pain.
f
Bruising or pinpoint dark red rash (NOT at injection site).
Table 3: Self-reported health events within 7 Days after dose 1 vaccination among vaccinated or during previous 7 Days among unvaccinated children and adolescents.
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was similar to or lower than their unvaccinated coun-
terparts. Health events were generally reported more
often after dose two than dose one. The risk of devel-
oping health events severe enough to prevent daily
activities, result in school absenteeism, or require a
medical consultation following the second dose was
higher among vaccinated adolescents (4.6 ─10.6%)
compared to unvaccinated adolescents (3.7%), and this
pattern was consistent across different vaccine prod-
ucts. When restricted to events resulting in emergency
department visits or hospitalizations, the proportions
of emergency care utilization among children and
adolescents were uncommon or rare across all vaccine
products and doses.
Our findings provide an understanding of mRNA
COVID-19 vaccine safety among pediatric populations
and results for short-term follow up were consistent
with previous clinical studies,
4,5,18
and post-marketing
studies.
6,7,19,20
Most studies focused on the safety of
mRNA COVID-19 vaccines in specific age groups. We
found one passive surveillance study from South Korea
that compared adverse events between children and
adolescents receiving the BNT162b2 vaccine, which
showed lower adverse event frequencies in children
Children (6 months–4 years) Children (5–11 years) Adolescent (12–19yrs)
BNT162b2
N=70
mRNA-1273
N = 2015
Mixed
N = 204
BNT162b2
N = 109,674
Mixed
N = 231
BNT162b2
N = 17,218
mRNA-1273
N = 1153
Mixed
N = 464
Injection site reactions reported with health
event
a
1 (1.4%) 89 (4.4%) 8 (3.9%) 2522 (2.3%) 7 (3.0%) 659 (3.8%) 86 (7.5%) 42 (9.1%)
General symptoms
Unwell
b
5 (7.1%) 119 (5.9%) 17 (8.3%) 2671 (2.4%) 10 (4.3%) 705 (4.1%) 90 (7.8%) 48 (10.3%)
Fever (≥38▫C) 5 (7.1%) 106 (5.3%) 14 (6.9%) 1420 (1.3%) 5 (2.2%) 351 (2%) 59 (5.1%) 27 (5.8%)
Febrile convulsion 0 (0%) 0 (0%) 0 (0%) 4 (<0.1%) 0 (0%) 2 (<0.1%) 0 (0%) 0 (0%)
GI symptoms
c
2 (2.9%) 53 (2.6%) 6 (2.9%) 1324 (1.2%) 4 (1.7%) 324 (1.9%) 47 (4.1%) 23 (5.0%)
Arthritis/joint pain/stiffness 1 (1.4%) 6 (0.3%) 0 (0%) 222 (0.2%) 2 (0.9%) 139 (0.8%) 28 (2.4%) 16 (3.4%)
Earache/ear pain/ear symptoms 1 (1.4%) 7 (0.3%) 0 (0%) 80 (0.1%) 0 (0%) 37 (0.2%) 5 (0.4%) 2 (0.4%)
Nasal congestion/sinus congestion 3 (4.3%) 72 (3.6%) 8 (3.9%) 754 (0.7%) 3 (1.3%) 139 (0.8%) 9 (0.8%) 10 (2.2%)
Runny nose 4 (5.7%) 77 (3.8%) 9 (4.4%) 736 (0.7%) 3 (1.3%) 112 (0.7%) 8 (0.7%) 2 (0.4%)
Sore throat 1 (1.4%) 13 (0.6%) 4 (2%) 984 (0.9%) 5 (2.2%) 166 (1%) 16 (1.4%) 7 (1.5%)
Neurologic symptoms
Headache or migraine 0 (0%) 28 (1.4%) 3 (1.5%) 2011 (1.8%) 6 (2.6%) 589 (3.4%) 76 (6.6%) 41 (8.8%)
Dizziness/vertigo/light-headedness 0 (0%) 4 (0.2%) 0 (0%) 240 (0.2%) 4 (1.7%) 187 (1.1%) 28 (2.4%) 18 (3.9%)
Fainting 0 (0%) 0 (0%) 0 (0%) 6 (<0.1%) 0 (0%) 18 (0.1%) 0 (0%) 3 (0.6%)
Loss of taste/smell 0 (0%) 2 (0.1%) 0 (0%) 42 (<0.1%) 0 (0%) 19 (0.1%) 2 (0.2%) 1 (0.2%)
Paresthesia 0 (0%) 1 (<0.1%) 0 (0%) 37 (<0.1%) 0 (0%) 40 (0.2%) 4 (0.3%) 5 (1.1%)
Seizure or convulsion 0 (0%) 0 (0%) 0 (0%) 9 (<0.1%) 0 (0%) 3 (<0.1%) 0 (0%) 0 (0%)
Other neurologic symptoms
d
0 (0%) 0 (0%) 0 (0%) 23 (<0.1%) 0 (0%) 11 (0.1%) 1 (0.1%) 0 (0%)
Coagulation symptoms
Symptoms of blood clot or bleeding
e
0 (0%) 0 (0%) 0 (0%) 11 (<0.1%) 0 (0%) 2 (<0.1%) 1 (0.1%) 0 (0%)
Bruising or pinpoint dark red rash
f
0 (0%) 1 (<0.1%) 0 (0%) 22 (<0.1%) 0 (0%) 5 (<0.1%) 0 (0%) 0 (0%)
Allergic-like symptoms
Rash or hives 0 (0%) 13 (0.6%) 0 (0%) 128 (0.1%) 0 (0%) 27 (0.2%) 5 (0.4%) 1 (0.2%)
Itchy or painful eyes 0 (0%) 10 (0.5%) 0 (0%) 134 (0.1%) 0 (0%) 58 (0.3%) 7 (0.6%) 2 (0.4%)
Tearing or eye discharge 1 (1.4%) 15 (0.7%) 0 (0%) 68 (0.1%) 0 (0%) 19 (0.1%) 2 (0.2%) 0 (0%)
Swelling of the throat and/or tongue 0 (0%) 1 (<0.1%) 0 (0%) 33 (<0.1%) 0 (0%) 17 (0.1%) 2 (0.2%) 1 (0.2%)
Cardiorespiratory
Chest tightness/discomfort/pain 0 (0%) 1 (<0.1%) 0 (0.0%) 115 (0.1%) 1 (0.4%) 95 (0.6%) 24 (2.1%) 7 (1.5%)
Rapid heart rate/palpitations 0 (0%) 1 (<0.1%) 1 (0.5%) 73 (0.1%) 1 (0.4%) 71 (0.4%) 14 (1.2%) 3 (0.6%)
Cough 4 (5.7%) 74 (3.7%) 10 (4.9%) 675 (0.6%) 3 (1.3%) 85 (0.5%) 10 (0.9%) 4 (0.9%)
Difficulty breathing 0 (0%) 6 (0.3%) 2 (1.0%) 104 (0.1%) 1 (0.4%) 79 (0.5%) 14 (1.2%) 5 (1.1%)
Data are n(%).
a
Participants who reported both injection site reaction and health events severe enough to result in prevention of daily activities, school absenteeism, or
requiring medical consultation. Only those who indicated a health event were asked to provide details of their symptoms. As symptoms are not mutually excluded,
participants can report more than one symptoms.
b
Tiredness, weakness, muscle aches, fatigue, or chills.
c
GI symptoms: Gastrointestinal symptoms such as nausea, vomiting,
diarrhea, or stomach pain.
d
Weakness or paralysis of the arms or legs, confusion, change in personality or behavior, or difficulty with urination or defecation.
e
Symptoms of
blood clot or bleeding, including swelling, pain in legs, or bruising or pinpoint dark rash; GI symptoms: nausea, vomiting, diarrhea, or stomach pain.
f
Bruising or pinpoint
dark red rash (NOT at injection site). Since only three children aged 5–11 years received the homologous mRNA-1273 vaccine, the results were not included in the table.
Table 4: Self-reported health events reported within 7 Days after dose 2 vaccination among vaccinated children and adolescents.
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10 www.thelancet.com Vol 40 December, 2024
aged 5–11 years than in adolescents aged 12–17 years
after either dose.
21
A systematic review and meta-
analysis pooled data to examine adverse reaction risks
of mRNA vaccine recipients, finding significantly
higher risks in adolescents aged 12–17 compared to
children aged 5–11.
9
Compared to previous evidence,
our findings, supported by a primary study with a
diverse pediatric sample, suggest that age-related
adverse event risks may be linked to the different
mRNA vaccine dosages recommended for children and
adolescents.
In our study, participant-reported or parents/
guardian reported cases of myocarditis/pericarditis
were identified within 0–28 days following vaccination,
with the highest incidence observed among male ado-
lescents after the second dose, consistent with the
current literature. Although these individuals required
emergency care or hospitalization, we have limited
Fig. 4: Onset of Health Events within 7 Days following Vaccination or previous 7 days among Vaccinated and Unvaccinated Children and
Adolescents. Since only 3 children aged 5–11 years received homologous mRNA-1273, the results were not included in the figure.
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information on specific laboratory or imagining re-
sults. While our data does not confirm these cases, the
demographic patterns, symptoms of onset, clinical
presentation and resolutions align with findings from a
systematic review and meta-analysis study, and large
population-based studies.
22–26
In the Canadian context,
a population-based study from Ontario reported a
higher rate of myocarditis/pericarditis in males aged
12–17 following the second doses of BNT162b2.
27
However, no data were reported for mRNA-1273
recipients in this age group as it was not used.
27
The
same study observed the highest reporting rates in
males aged 18–24 years following mRNA-1273 as the
second dose.
27
Another study
28
using Canadian passive
surveillance data confirmed a higher risk of myocar-
ditis and/or pericarditis after mRNA-1273 than
BNT162b2 in males aged 18–29 years. Although our
study included a limited sample of mRNA-1273 re-
cipients aged 19 and below, we detected three cases
following the second dose of mRNA-1273 (two after
Fig. 5: Duration of health events within 7 days following vaccination or previous 7 days among vaccinated and unvaccinated children and
adolescents. Since only 3 children aged 5–11 years received homologous mRNA-1273, the results were not included in the figure.
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12 www.thelancet.com Vol 40 December, 2024
homologous mRNA-1273 and one after heterologous
BNT162b2-mRNA-1273).
In the 7-month follow up, reported emergency care
utilizations were higher among children under 5 years
of age than older children or adolescents. This pattern is
consistent between vaccinated and unvaccinated groups,
and aligned with emergency department visits from
Canadian National Ambulatory Care Reporting Sys-
tem.
29
Reassuringly, hospitalizations within 7 months
following the first dose, or within 6 months prior to the
survey among controls, were uncommon in both vacci-
nated and unvaccinated groups. Additionally no
considerable increase in emergency care utilization was
observed during the longer follow-up period. A popu-
lation based study from an Italy reported that one or
more doses of mRNA COVID-19 vaccines in individuals
aged 6 years and above was not associated with an
increased risk of death from any cause, or any poten-
tially vaccine-related serious adverse events requiring
hospitalization within an average follow-up period of 14
months.
30
Our findings provide insights into the short- and
medium-term safety of mRNA COVID-19 vaccines
across the pediatric age spectrum. When assessing
vaccine safety, it is crucial to consider both vaccine-
associated adverse events as well as the risks and out-
comes associated with infection. While our study
focused on adverse events following immunization,
other research highlights the risk–benefit profile of
COVID-19 vaccination in children and adolescents. For
instance, a recent population-based study from the US
indicated that vaccination against COVID-19 in children
aged 5–17 years is associated with a reduced risk of post
COVID conditions, with a stronger effect in adoles-
cents.
31
Moreover, a self-controlled case-series study
involving linked data of 5.1 million children in England
revealed that SARS-CoV-2 infection increased the risk of
hospitalization for seven outcomes, including multi-
system inflammatory syndrome and myocarditis; how-
ever, these risks were absent or reduced in children
vaccinated prior to infection.
32
These findings assist in
guiding vaccination decision-making by balancing the
benefits and risks of vaccinations, especially among
adolescents.
Our study participants self-selected to participate,
and the majority were White, which may limit the
generalizability of our findings to the broader popula-
tion of children and adolescents. However, our sample
had similar characteristics (sex, health status and resi-
dence) to the Canadian pediatric population.
33,34
The sex
distribution (45.3–49.6% female in our study vs 48.8%
nationally)
34
and health status (91–94% in our study vs
90.9% nationally),
33
align closely with national data, for
both vaccinated and unvaccinated groups. Additionally,
most our data were collected from Canada’s most
populous provinces: Quebec, Ontario, British Columbia,
and Alberta.
34
CANVAS relies on participant-based reporting
without verification from medical records, which is
subject to reporting or recall bias. In particular, differ-
ential recall bias is a concern; vaccinated participants
may be more likely to recall adverse events following
vaccination in assessments covering both short and
longer periods compared to their unvaccinated coun-
terparts. Furthermore, both groups may have poor recall
regarding emergency care utilization in questionnaires
interrogating longer periods.
Another important limitation is the limited sample
sizes for unvaccinated controls across all age groups and
for vaccinated individuals receiving mRNA-1273 vac-
cines (children aged 5–11), and those who received
mixed schedules. The smaller unvaccinated sample size
may be due to recruitment strategies. The limited
number of children aged 5–11 receiving mRNA-1273
may be related to our recruitment timing, as
BNT162b2 was approved for children in November
2021, while mRNA-1273 was only approved in March
2022.
3
Most children in our sample were recruited be-
tween December 2021 and February 2022, aligning with
the availability of BNT162b2.
Additionally, unvaccinated children and adolescents
were recruited a few months earlier than vaccinated
groups, which may have reduced comparability be-
tween vaccinated and control groups. We observed a
high proportion of health events reported in the 7 days
prior to the survey among the unvaccinated control
groups. This may be related to delayed vaccination and
circulating SARS-CoV-2 variants. In general, unvacci-
nated adolescents were recruited before the Omicron
period, while unvaccinated children were recruited
during the Omicron period. Although similar pro-
portions of participants reported past SARS-CoV-2
infection in both unvaccinated and vaccinated chil-
dren under 5 years of age, higher proportions of un-
vaccinated children aged 5–11 years and adolescents
reported past infection compared to their vaccinated
counterparts for both doses. Despite adjusting for
previous SARS-COV-2 infection status in multivariable
models, we did not differentiate whether these in-
fections were recent or distant. This limitation may
have led to underestimation of the risk of health events
associated vaccination.
Although efforts were made to control for con-
founders and risk factors in the multivariable regression
models, there may be residuals or unmeasured con-
founders. We also recognized the potential influence of
ethnicity on reactogenicity and reporting adverse events.
However, the ethnicity question was included in the
survey for the second dose among adolescents. Conse-
quently, this information was not available for most
unvaccinated and dose 1 adolescent participants,
limiting our ability to consistently adjust for this variable
in all regression models. Although ethnicity was
included in our multivariable models for children under
Articles
www.thelancet.com Vol 40 December, 2024 13
5 and those aged 5–11, results did not significantly differ
with or without this variable (data not shown).
Furthermore, to reduce participant burden, our surveys
did not collect data on individual-level variables such as
body weight, comorbidities for all age groups, or age as a
continuous variable for adolescents, limiting their in-
clusion in our analyses.
Finally, not all participants from the dose one survey
completed dose two and follow-up surveys. Attrition was
slightly higher among those who reported experiencing
health events after dose one. This differential drop-out
may have led to underestimations in the estimates
from dose two and the follow-up surveys. Despite these
limitations, our results complement ongoing vaccine
pharmacovigilance systems (passive surveillance) in
Canada and elsewhere.
One strength of this study was the inclusion of three
pediatric age groups eligible for COVID-19 vaccines.
This enabled us to examine the age-stratified risk asso-
ciated with each vaccine product used in Canada.
Another strength was the recruitment of non-vaccinated
children and adolescents, which enabled the assessment
of events in unvaccinated groups. The longer-term
follow-up surveys allowed us to examine emergency
care utilization patterns and incidence of pericarditis/
myocarditis among pediatric populations through 7
months following dose one.
In conclusion, our findings support the safety of
mRNA COVID-19 vaccines for children and adoles-
cents. Similar to vaccinated adults, our findings showed
that vaccinated adolescents reported higher proportions
of health events after the second dose of mRNA COVID-
19 vaccines. Our study detected rare adverse events of
special interest, including myocarditis and pericarditis,
with similar epidemiology confirmed in multiple large
population-based studies. Through 7 months of follow-
up, there was no increase in emergency department
visit/hospitalization in vaccinated participants compared
to controls. Our findings can be used to inform safety
profiles of COVID-19 vaccines among the youngest
population eligible for COVID-19 vaccines in Canada
and globally and help inform adolescents and parents
about what to expect following COVID-19 vaccination.
Contributors
JAB designed, implemented, and oversaw the study, supervised PS and
shares senior and corresponding authorship. PS developed the analysis
plan, contributed to data analysis, produced data tables and figures,
interpreted the data and drafted the manuscript. OGV developed the
analysis plan, interpreted the data and reviewed the manuscript and
shares senior and corresponding authorship. KM and HS cleaned and
analyzed the data. Together with JAB, GDS, MPM, JDK, KM, JDK, MS,
AM, OGV, LV and KAT implemented study and all contributed equally
to this work. HW and MN supervised PS and reviewed the analysis plan
and manuscript. All authors read, revised, and approved the manuscript.
Data sharing statement
De-identified data collected for the study (with data dictionary) may be
made available upon approval by the study investigators, with relevant
agreements (e.g., data sharing agreement) and approvals (e.g., relevant
ethics approvals). Requests should be directed to the corresponding
author in the first instance.
Declaration of interests
GDS, HS, HW, LV, MN, KM and OGV have no competing interests. PS
received personal payments for consulting from the Joint United Nations
Programme on HIV/AIDS outside the submitted work. MS has been an
investigator on projects funded by GlaxoSmithKline, Merck, Moderna,
Pfizer and Sanofi-Pasteur outside the submitted work. All funds were paid
to his institute, and he has not received any personal payments. MPM
received payment testifying as an expert with respect to mandatory
influenza and COVID-19 vaccination in healthcare settings. JDK has been
an investigator on projects funded by Moderna Canada and Alberta
Children’s Hospital Research Institute and Government of Alberta, all
outside the submitted work. All funds have been paid to his institute, and
he has not received any personal payments. KAT reports grants from
Canadian Institute of Health Research and the Coalition of Epidemic
Preparedness Innovations for COVID-19 vaccine studies. KAT received
personal payments for consulting from World Health Organization. JEI
has been an investigator on projects funded by GlaxoSmithKline and
Sanofi-Pasteur outside the submitted work. All funds were paid to her
institute, and she has not received any personal payment. AM reports
grants to her institution from Pfizer, Merck, Sanofi, and Seqirus, as well
as personal payments for consulting or honoraria from Sienna Senior
Living, AstraZeneca, Merck, Biogen, Sanofi, GlaxoSmithKline, Moderna,
Medicago, Janssen, Novavax, Pfizer, and Seqirus. JAB has served on the
Research Leadership Committee at BC Children’sHospitalResearch
Institute and the National Advisory Committee on Immunization.
Acknowledgements
We would like to express our sincere appreciation to all study partici-
pants who made this study possible. Thanks to our provincial/territorial
collaborators and other collaborators from Canadian Immunization
Research Network.
We would like to thank the organizers of the Healthy Start Research
Day, held in in-person at the Chan Center, BC Children’s Hospital
Research Institute, on February 9th, 2024, and the Canadian Paediatric
Society’s Annual Conference, taking place June 6–8, 2024 in Vancouver,
for providing a platform to present our research.
Funding: The CANVAS-COVID study was supported by the
COVID-19 Vaccine Readiness funding from the Canadian Immuniza-
tion Research Network, the Canadian Institutes of Health Research and
the Public Health Agency of Canada CANVAS grant number CVV-
450980. Additional support came from the Public Health Agency of
Canada, through the Vaccine Surveillance Reference group and the
COVID-19 Immunity Task Force.
PS was supported by a Doctoral Studentship Award from BC
Children’s Hospital Research Institute and Canadian Immunization
Research Network Trainee Award. MS is supported via salary awards
from the BC Children’s Hospital Foundation and Michael Smith Health
Research BC.
Appendix A. Supplementary data
Supplementary data related to this article can be found at https://doi.
org/10.1016/j.lana.2024.100949.
References
1 Farrar DS, Drouin O, Moore Hepburn C, et al. Risk factors for
severe COVID-19 in hospitalized children in Canada: a national
prospective study from March 2020-May 2021. Lancet Reg Health
Am. 2022. https://doi.org/10.1016/j.lana.2022.100337.
2 Lopez-Leon S, Wegman-Ostrosky T, Ayuzo del Valle NC, et al.
Long-COVID in children and adolescents: a systematic review and
meta-analyses. Sci Rep. 2022 2022/06/23;12(1):9950. https://doi.
org/10.1038/s41598-022-13495-5.
3 Government of Canada. Drug and vaccine authorizations for COVID-
19: list of authorized drugs, vaccines and expanded indications; 2023
[cited 2023 December 1]; Available from: https://www.canada.ca/
en/health-canada/services/drugs-health-products/covid19-industry/
drugs-vaccines-treatments/authorization/list-drugs.html.
Articles
14 www.thelancet.com Vol 40 December, 2024
4 Anderson EJ, Creech CB, Berthaud V, et al. Evaluation of mRNA-
1273 vaccine in children 6 Months to 5 Years of age. N Engl J Med.
2022;387(18):1673–1687. https://doi.org/10.1056/NEJMoa2209367.
5 Walter EB, Talaat KR, Sabharwal C, et al. Evaluation of the BNT162b2
covid-19 vaccine in children 5 to 11 Years of age. N Engl J Med.
2022;386(1):35–46. https://doi.org/10.1056/NEJMoa2116298.
6 Hause AM, Shay DK, Klein NP, et al. Safety of COVID-19 vacci-
nation in United States children ages 5 to 11 years. Pediatrics.
2022;150(2):2022–57313. https://doi.org/10.1542/peds.2022-
057313.
7 Hesse EM, Hause A, Myers T, et al. COVID-19 vaccine safety first
year findings in adolescents. Pediatrics. 2023;151(5):2022–60295.
https://doi.org/10.1542/peds.2022-060295.
8 Du Y, Chen L, Shi Y. Safety, immunogenicity, and efficacy of
COVID-19 vaccines in adolescents, children, and infants: a sys-
tematic review and meta-analysis. Front Public Health. 2022.
https://doi.org/10.3389/fpubh.2022.829176. eCollection 2022.
9 Bettinger JA, De Serres G, Valiquette L, et al. 2017/18 and 2018/19
seasonal influenza vaccine safety surveillance, Canadian National
Vaccine Safety (CANVAS) Network. Euro Surveill. 2020;25(22):1560–
7917. https://doi.org/10.2807/1560-7917.ES.2020.25.22.1900470.
10 Ahmed MA, Naus M, Singer J, et al. Investigating the association of
receipt of seasonal influenza vaccine with occurrence of anesthesia/
paresthesia and severe headaches, Canada 2012/13-2016/17, the
Canadian Vaccine Safety Network. Vaccine. 2020;38(19):3582–3590.
https://doi.org/10.1016/j.vaccine.2020.03.018.
11 Bettinger JA, Sadarangani M, De Serres G, et al. The Canadian Na-
tional Vaccine Safety Network: surveillance of adverse events
following immunisation among individuals immunised with the
COVID-19 vaccine, a cohort study in Canada. BMJ Open. 2022;12(1):
e051254. https://doi.org/10.1136/bmjopen-2021-051254.
12 Soe P, Sadarangani M, Naus M, et al. Impact of recruitment stra-
tegies on individual participation practices in the Canadian Na-
tional Vaccine Safety Network: prospective cohort study. Front
Public Health. 2024;12:1385426. https://doi.org/10.3389/fpubh.
2024.1385426.
13 Government of Canada. Archived 2: recommendations on the use of
COVID-19 vaccines [2020-12-23]; 2020 [cited 2024 September 12];
Available from: https://www.canada.ca/en/public-health/services/
immunization/national-advisory-committee-on-immunization-naci/
recommendations-use-covid-19-vaccines/december-23-2020.html.
14 Government of Canada. Archived 5: NACI rapid response: extended
dose intervals for COVID-19 vaccines to optimize early vaccine rollout
and population protection in Canada [2021-03-03]; 2021. Available
from: https://www.canada.ca/en/public-health/services/immun
ization/national-advisory-committee-on-immunization-naci/rapid-
response-extended-dose-intervals-covid-19- vacc ines -ear ly-r ollo ut-
population-protection.html.
15 Sexson Tejtel SK, Munoz FM, Al-Ammouri I, et al. Myocarditis and
pericarditis: case definition and guidelines for data collection, analysis,
and presentation of immunization safety data. Vaccine.
2022;40(10):1499–1511. https://doi.org/10.1016/j.vaccine.2021.11.074.
16 Gold MS, Amarasinghe A, Greenhawt M, et al. Anaphylaxis: revi-
sion of the Brighton collaboration case definition. Vaccine.
2023;41(15):2605–2614. https://doi.org/10.1016/j.vaccine.2022.11.
027.
17 European Medicines agency. Spikevax (previously COVID-19 vaccine
Moderna): EPAR - medicine overview; 2023 [cited 2024 September 1];
Available from: https://www.ema.europa.eu/en/documents/
overview/spikevax-previously-covid-19-vaccine-moderna-epar-medi-
cine-overview_en.pdf.
18 Frenck RW Jr, Klein NP, Kitchin N, et al. Safety, immunogenicity,
and efficacy of the BNT162b2 covid-19 vaccine in adolescents.
N Engl J Med. 2021;385(3):239–250. https://doi.org/10.1056/
NEJMoa2107456.
19 Capponi M, Pulvirenti F, Cinicola BL, et al. Short-term side effects
and SARS-CoV-2 infection after COVID-19 pfizer-BioNTech vac-
cine in children aged 5-11 Years: an Italian real-world study. Vac-
cines. 2022;10(7). https://doi.org/10.3390/vaccines10071056.
20 Kim S, Hwang I, Ko M, Kwon Y, Lee YK. Safety monitoring of
COVID-19 vaccination among adolescents aged 12 to 17 years old
in the Republic of Korea. Osong Public Health Res Perspect.
2022;13(3):230–237.
21 Kim S, Heo Y, Seo SY, Lim DS, Cho E, Lee YK. Adverse events of
the Pfizer-BioNTech COVID-19 vaccine in Korean children and
adolescents aged 5 to 17 years. Osong Public Health Res Perspect.
2022;13(5):382–390.
22 Massari M, Spila Alegiani S, Morciano C, et al. Postmarketing
active surveillance of myocarditis and pericarditis following vacci-
nation with COVID-19 mRNA vaccines in persons aged 12 to 39
years in Italy: a multi-database, self-controlled case series study.
PLoS Med. 2022;19(7). https://doi.org/10.1371/journal.pmed.
1004056.
23 Karlstad Ø, Hovi P, Husby A, et al. SARS-CoV-2 vaccination and
myocarditis in a nordic cohort study of 23 million residents. JAMA
Cardiol. 2022;7(6):600–612. https://doi.org/10.1001/jamacardio.
2022.0583.
24 Hu M, Shoaibi A, Feng Y, et al. Safety of ancestral monovalent
BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 vaccines in
US children aged 6 Months to 17 years. JAMA Netw Open.
2024;7(4). https://doi.org/10.1001/jamanetworkopen.2024.8192.
25 Klein NP, Lewis N, Goddard K, et al. Surveillance for adverse events
after COVID-19 mRNA vaccination. JAMA. 2021;326(14):1390–
1399. https://doi.org/10.1001/jama.2021.15072.
26 Thenpandiyan AA, Ling RR, Grignani R, et al. Myopericarditis
following COVID-19 vaccination in children: a systematic review
and meta-analysis. Singapore Med J. 2024;3(10):2023–2081. https://
doi.org/10.4103/singaporemedj.SMJ-2023-081.
27 Buchan SA, Seo CY, Johnson C, et al. Epidemiology of myocarditis
and pericarditis following mRNA vaccination by vaccine product,
schedule, and interdose interval among adolescents and adults in
Ontario, Canada. JAMA Netw Open. 2022;5(6):18505. https://doi.
org/10.1001/jamanetworkopen.2022.18505.
28 Abraham N, Spruin S, Rossi T, et al. Myocarditis and/or pericar-
ditis risk after mRNA COVID-19 vaccination: a Canadian head to
head comparison of BNT162b2 and mRNA-1273 vaccines. Vaccine.
2022;40(32):4663–4671. https://doi.org/10.1016/j.vaccine.2022.05.
048.
29 Information CIfH. NACRS emergency department visits and lengths of
stay; 2024 [cited 2024 April 16]; Available from: https://www.cihi.
ca/en/nacrs-emergency-department-visits-and-lengths-of-stay.
30 Flacco ME, Acuti Martellucci C, Soldato G, et al. COVID-19 vacci-
nation did not increase the risk of potentially related serious
adverse events: 18-month cohort study in an Italian province.
Vaccines. 2022;11(1). https://doi.org/10.3390/vaccines11010031.
31 Razzaghi H, Forrest CB, Hirabayashi K, et al. Vaccine effectiveness
against long COVID in children. Pediatrics. 2024;153(4):
e2023064446. https://doi.org/10.1542/peds.2023-064446.
32 Copland E, Patone M, Saatci D, et al. Safety outcomes following
COVID-19 vaccination and infection in 5.1 million children in
England. Nat Commun. 2024;15(1):5723. https://doi.org/10.1038/
s41467-024-50151-0.
33 Statistics Canada. Health of Canadians Health outcomes General
and mental health status 2021 [cited 2024 September 18]; Available
from: https://www150.statcan.gc.ca/n1/pub/82-570-x/2023001/
section1-eng.htm.
34 Statistics Canada. Annual demographic estimates: Canada, provinces
and territories, 2022; 2022 [cited 2024 October 4]; Available from:
https://www150.statcan.gc.ca/n1/pub/91-215-x/2022001/sec2-eng.
htm.
Articles
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