MYOCARDITIS AFTER SARS-COV-2 VACCINATION: TRUE, TRUE, AND RELATED? - AMERICAN ...
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Myocarditis After SARS-CoV-2
Vaccination: True, True, and …
Related?
Sean T. O’Leary, MD, MPH,a,b Yvonne A. Maldonado, MDc
In this month’s issue of Pediatrics, compiled cases through personal
Marshall et al report a case series communication rather than through
describing seven 14- to 19-year-old a systematic surveillance system.
male individuals who developed Clearly, this approach could
symptomatic myocarditis after the introduce reporting bias, and a case
second dose of the Pfizer-BioNTech series cannot establish causality.
coronavirus disease 2019 (COVID- Another critical point to consider is
19) vaccine.1 The authors report that that the reported cases mirror the
the symptoms began between 2 and seasonal prevalence, sex, and age
4 days after the second dose and that profile of background cases of a
Adult and Child Consortium for Health Outcomes
all 7 patients experienced rapid myocarditis, thereby complicating an Research and Delivery Science, Anschutz Medical Campus,
resolution of symptoms. This case assessment of a potential association University of Colorado and Children’s Hospital Colorado,
Aurora, Colorado, bDepartment of Pediatrics, Anschutz
series is published in the context of with SARS-CoV-2 vaccines. The Medical Campus, University of Colorado, Aurora, Colorado,
other media reports of myocarditis authors themselves note in their c
Department of Pediatrics, School of Medicine, Stanford
in young adults, mostly male, from discussion the high background rate University, Stanford, California
the US military and from Israel2 as of myocarditis in adolescent and Opinions expressed in these commentaries are those of
well as a recent increase in reports young adult male individuals,4 the authors and not necessarily those of the American
Academy of Pediatrics or its Committees.
of myocarditis after serious acute precisely the population in this case
DOI: https://doi.org/10.1542/peds.2021-052644
respiratory syndrome coronavirus 2 series. Thus, a causal relationship
Accepted for publication Jun 1, 2021
(SARS-CoV-2) vaccines to the Food between the Pfizer-BioNTech vaccine
Address correspondence to Sean T. O’Leary, MD, MPH
and Drug Administration (FDA) and and myocarditis based on sporadic University of Colorado, Department of Pediatrics Mail Stop
the Centers for Disease Control and clinical reports must be promptly F443 13199 E Montview Blvd, Suite 300 Aurora CO 80045.
E-mail: sean.oleary@cuanschutz.edu
Prevention (CDC) Vaccine Adverse investigated further by using a
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
Event Reporting System (VAERS).3 robust and structured surveillance 1098-4275).
As such, this case series offers useful platform, such as that provided by Copyright © 2021 by the American Academy of Pediatrics
preliminary information on clinical CDC VAERS. FINANCIAL DISCLOSURE: The authors have indicated
and therapeutic details regarding they have no financial relationships relevant to this
Because of the severity of the article to disclose.
myocarditis among adolescents.
pandemic and the urgent need for FUNDING: No external funding.
Although the authors are quick to suppression and control, vaccines POTENTIAL CONFLICT OF INTEREST: Dr Maldonado is the
point out that a causal relationship against SARS-CoV-2 have been site Principal Investigator for a Pfizer COVID-19 vaccine
clinical trial in children and a Pfizer respiratory
between vaccination and myocarditis delivered to the US population with syncytial virus vaccine clinical trial in pregnant women.
has not been established, the unprecedented speed and scale, She is a member of a Data Safety Monitoring Board for
a Pfizer non-COVID-19 vaccine clinical trial. Dr O’Leary
temporal association of these cases undoubtedly saving many thousands has no relevant conflicts of interest to disclose.
with vaccination as well as the of lives as a result. Although there COMPANION PAPER: A companion to this article can be
striking similarity in the clinical and was consensus among the scientific found online at www.pediatrics.org/cgi/doi/10.1542/
2021-052478.
laboratory presentations raise the and public health communities that
possibility for such a relationship. rapid dissemination of SARS-CoV-2
To cite: O’Leary ST, Maldonado YA. Myocarditis
However, the authors also vaccines was necessary after
After SARS-CoV-2 Vaccination: True, True, and …
acknowledge that a significant Emergency Use Authorization by the Related?. Pediatrics. 2021;148(3):e2021052644
limitation in their report is that they FDA, there were potential risks in
Downloaded from www.aappublications.org/news by guest on November 2, 2021
PEDIATRICS Volume 148, number 3, September 2021:e2021052644 COMMENTARYdoing so. Specifically, clinical trials Datalink, as well as new systems following smallpox vaccination.” In
for vaccines, or any biological such as V-Safe that added further fact, although myocarditis has been
product, are highly unlikely to surveillance capacity. Indeed, the reported as an adverse event after
detect rare adverse events. The identification of a rare risk of other vaccinations, smallpox
clinical trials for SARS-CoV-2 anaphylaxis after the Pfizer- vaccination is the only vaccine that
vaccines were actually larger than BioNTech and Moderna vaccines7,8 has ever been conclusively linked to
for most vaccines and certainly most and of cerebral venous sinus myocarditis on the basis of a
medications, with 30 000 to thrombosis after the Janssen significantly higher relative risk.10 It
45 000 participants for each of the 3 vaccine9 within literally a matter of is worth noting that smallpox is a
vaccines currently authorized in the days after rollout validate the live vaccine and is associated with
United States. Safety profiles in efficacy of the US safety surveillance more adverse events than vaccines
those trials were very favorable, systems. in the routine schedule.11 Thus, if
which is reassuring, but the sample myocarditis after vaccination were
sizes of the trials were not large Both VAERS and Vaccine Safety confirmed to be a causally related
enough to detect possible adverse Datalink have rapidly provided rare adverse event after SARS-CoV-2
events with an incidence of, for information to the general US vaccination, it would be unique
population about specific potential
example, 1 case in 100 000 doses. among nonlive vaccines, so that
adverse events consequent to SARS-
Thus, the risk of such rare adverse gaining an understanding of the
CoV-2 vaccines (known as
events must be outweighed by the underlying biological mechanism
“prespecified outcomes” in the
benefits of the proposed would be important. Typically, the
vaccine safety system).6 Among
intervention. With >4 million pathogenesis of viral myocarditis
these outcomes are myocarditis and
COVID-19 cases diagnosed in involves direct viral infection of the
pericarditis. According to the CDC,
children 166 million
that resulted in >15 000 invoked as a cause in these reported
doses of COVID-19 vaccines have
hospitalizations and between 300 cases. In vaccinia-associated
been administered in the United
and 600 deaths, the benefits of myopericarditis, an autoimmune
States, with 2.5 million doses of the
vaccination in this population far phenomenon is suspected,12 but the
Pfizer-BioNTech delivered to
exceed the risks of rare adverse time to onset of symptoms after
adolescents 12 to 15 years of age in
events.5 just the 2 weeks since it was vaccination is typically >1
approved for use in this age group week,13,14 much longer than the
Because vaccines are generally current case series. If a causal
and 4 million doses given to 16 to
administered to healthy populations, relationship between myocarditis
18 years since FDA Emergency Use
they are held to a much higher and SARS-CoV-2 vaccination is
Authorization approval in December
safety standard than most other identified, a different biological
2020. Despite this widespread and
biological products that might be mechanism is likely responsible and
rapid vaccine uptake especially
given as therapeutics. However, will need investigation.
among childrencontext of a dearth of circulation of disease clearly far outweigh any 6. Lee GM, Romero JR, Bell BP. Postapproval
common respiratory viruses known potential risks. Finally, rapid and vaccine safety surveillance for COVID-19
to be associated with myocarditis, robust real-time analysis of existing vaccines in the US. JAMA. 2020;324(19):
and thorough diagnostic evaluations surveillance data should be reported 1937–1938
did not identify infectious etiologies. as quickly as possible through the 7. CDC COVID-19 Response Team; Food and
Although the number of cases in this VAERS system and other national Drug Administration. Allergic reactions
series is small and subject to surveillance to provide confidence in including anaphylaxis after receipt of the
reporting bias, scientists should the nature of the safety profile of first dose of Pfizer-BioNTech COVID-19 vac-
rapidly address any possible SARS-CoV-2 vaccines in the pediatric cine - United States, December 14-23,
association of myocarditis and population. 2020. MMWR Morb Mortal Wkly Rep.
COVID-19 vaccinations through 2021;70(2):46–51
continuing analyses within our 8. CDC COVID-19 Response Team; Food and
national surveillance systems. Drug Administration. Allergic reactions
ABBREVIATIONS
Investigators should also consider including anaphylaxis after receipt of the
the timing of the first dose of the COVID-19: coronavirus disease first dose of Moderna COVID-19 Vaccine -
vaccine relative to reported cases of 2019 United States, December 21, 2020-Janu-
myocarditis, which the authors do CDC: Centers for Disease Control ary 10, 2021. MMWR Morb Mortal Wkly
not report in this case series. and Prevention Rep. 2021;70(4):125–129
Although these patients did not FDA: Food and Drug 9. Shay DK, Gee J, Su JR, et al. Safety moni-
meet criteria for the multisystem Administration toring of the Janssen (Johnson & John-
inflammatory syndrome in children MIS-C: multisystem inflammatory son) COVID-19 Vaccine - United States,
(MIS-C), the unusual cardiac syndrome in children March-April 2021. MMWR Morb Mortal
manifestations and generally quick SARS-CoV-2: serious acute Wkly Rep. 2021;70(18):680–684
resolution of symptoms in both this respiratory 10. Dudley MZ, Halsey NA, Omer SB, et al. The
case series and in many children syndrome state of vaccine safety science: system-
with MIS-C suggests a possible coronavirus 2 atic reviews of the evidence. Lancet
common pathogenesis. Given that VAERS: Vaccine Adverse Event Infect Dis. 2020;20(5):e80–e89
MIS-C typically happens 3 to 5 Reporting System
11. Casey C, Vellozzi C, Mootrey GT, et al; Vac-
weeks after a SARS-CoV-2 infection, cinia Case Definition Development Work-
we must also consider the ing Group; Advisory Committee on
possibility that the first dose is the REFERENCES Immunization Practices-Armed Forces
initiating factor. 1. Marshall M, Ferguson ID, Lewis P, et al. Epidemiological Board Smallpox Vaccine
Symptomatic acute myocarditis in seven Safety Working Group. Surveillance guide-
Despite the current lack of a adolescents following Pfizer-BioNTech lines for smallpox vaccine (vaccinia)
definitive association between COVID19. Pediatrics. 2021;148(3): adverse reactions. MMWR Recomm Rep.
myocarditis and SARS-CoV-2 e2021052478 2006;55(RR-1):1–16
vaccines, a few key points can be 2. Times of Israel. Israel said probing link 12. Cassimatis DC, Atwood JE, Engler RM,
communicated to pediatricians and between Pfizer shot and heart problem in Linz PE, Grabenstein JD, Vernalis MN.
to the public at large. First, the men under 30. Times Israel. April 23, 2021 Smallpox vaccination and myopericardi-
reported cases of myocarditis 3. Centers for Disease Control and Preven- tis: a clinical review. J Am Coll Cardiol.
appear to be mild in nature and tion. Clinical considerations: myocarditis 2004;43(9):1503–1510
respond rapidly to minimally and pericarditis after receipt of mRNA 13. Morgan J, Roper MH, Sperling L, et al.
invasive therapy. Second, any COVID-19 vaccines among adolescents Myocarditis, pericarditis, and dilated car-
potential association between and young adults. https://www.cdc.gov/ diomyopathy after smallpox vaccination
myocarditis and SARS-CoV-2 vaccines/covid-19/clinical-considerations/ among civilians in the United States, Jan-
vaccination will likely be rare given myocarditis.html. Accessed May 28, 2021 uary-October 2003. Clin Infect Dis.
that our national safety surveillance 4. Fung G, Luo H, Qiu Y, Yang D, McManus B. 2008;46(Suppl 3):S242–S250
systems have not yet identified a Myocarditis. Circ Res. 2016;118(3):496–514 14. Halsell JS, Riddle JR, Atwood JE, et al;
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PEDIATRICS Volume 148, number 3, Downloaded
September 2021
from www.aappublications.org/news by guest on November 2, 2021 3Myocarditis After SARS-CoV-2 Vaccination: True, True, and… Related?
Sean T. O'Leary and Yvonne A. Maldonado
Pediatrics originally published online June 4, 2021; originally published online June
4, 2021;
Updated Information & including high resolution figures, can be found at:
Services http://pediatrics.aappublications.org/content/early/2021/08/12/peds.2
021-052644
References This article cites 12 articles, 4 of which you can access for free at:
http://pediatrics.aappublications.org/content/early/2021/08/12/peds.2
021-052644#BIBL
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Downloaded from www.aappublications.org/news by guest on November 2, 2021Myocarditis After SARS-CoV-2 Vaccination: True, True, and… Related?
Sean T. O'Leary and Yvonne A. Maldonado
Pediatrics originally published online June 4, 2021; originally published online June
4, 2021;
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/early/2021/08/12/peds.2021-052644
Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. Pediatrics is owned, published, and trademarked by
the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2021
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