Myocarditis in SARS-CoV-2 infection vs. COVID-19 vaccination: A systematic review and meta-analysis

2022·2.3 MB·English

by  Navya Voleti, Surya Prakash Reddy, Paddy Ssentongo

TYPE OriginalResearch
PUBLISHED 29August2022
DOI 10.3389/fcvm.2022.951314
Myocarditis in SARS-CoV-2
infection vs. COVID-19
OPENACCESS
EDITEDBY vaccination: A systematic review
MairajAhmedAnsari,
JamiaHamdardUniversity,India
and meta-analysis
REVIEWEDBY
TinhinaneFali,
InstitutNationaldelaSantéetdela
RechercheMédicale(INSERM),France
BibhitiDas, NavyaVoleti1, SuryaPrakashReddy2 andPaddySsentongo1,3*
UniversityofMississippiMedical
Center,UnitedStates 1DepartmentofMedicine,PennStateHealthMedicalCenter,Hershey,PA,UnitedStates,
2DepartmentofMedicine,OsmaniaMedicalCollege,Hyderabad,India,3DepartmentofPublic
*CORRESPONDENCE HealthSciences,PennStateCollegeofMedicine,Hershey,PA,UnitedStates
PaddySsentongo
[email protected]
SPECIALTYSECTION Background: This study aimed to compare the incidence of myocarditis in
Thisarticlewassubmittedto
CardiovascularEpidemiologyand COVID-19 vaccines and in severe acute respiratory syndrome-coronavirus 2
Prevention, (SARS-CoV-2)infectiongroups.
asectionofthejournal
FrontiersinCardiovascularMedicine Methods: Electronicdatabases(MEDLINE,Scopus,CochraneCentralRegister
RECEIVED23May2022 ofControlledTrials,CochraneDatabaseofSystematicReviews,andtheWHO
ACCEPTED11July2022 GlobalLiteratureonCoronavirusDisease)andtrialregistriesweresearchedup
PUBLISHED29August2022 toMay2022,forrandomizedcontrolledtrialsandobservationalcohortstudies
CITATION reportingtheriskofmyocarditisassociatedwiththeCOVID-19vaccinesand
VoletiN,ReddySPandSsentongoP
(2022)MyocarditisinSARS-CoV-2 the risk associated with SARS-CoV-2 infection. We estimated the effect of
infectionvs.COVID-19vaccination:A COVID-19infectionandvaccinesonratesofmyocarditisbyrandom-effects
systematicreviewandmeta-analysis.
Front.Cardiovasc.Med.9:951314. meta-analyses using the generic inverse variance method. Meta-regression
doi:10.3389/fcvm.2022.951314 analyseswereconductedtoassesstheeffectofsexandageontheincidence
ofmyocarditis.
COPYRIGHT
©2022 Voleti,ReddyandSsentongo.
Results: Weidentified22eligiblestudiesconsistingof55.5millionvaccinated
Thisisanopen-accessarticle
distributedunderthetermsofthe cohorts and 2.5 million in the infection cohort. The median age was 49
CreativeCommonsAttributionLicense years(interquartilerange(IQR):38–56),and49%(IQR:43to52%)weremen.
(CCBY).Theuse,distributionor
reproductioninotherforumsis Of patients diagnosed with myocarditis (in both vaccination and COVID-19
permitted,providedtheoriginal cohort) 1.07% were hospitalized and 0.015% died. The relative risk (RR) for
author(s)andthecopyrightowner(s)
myocarditiswasmorethanseventimeshigherintheinfectiongroupthanin
arecreditedandthattheoriginal
publicationinthisjournaliscited,in thevaccinationgroup[RR:15(95%CI:11.09–19.81,infectiongroup]andRR:
accordancewithacceptedacademic 2(95%CI:1.44-2.65,vaccinegroup).Ofpatientswhodevelopedmyocarditis
practice.Nouse,distributionor
after receiving the vaccine or having the infection, 61% (IQR: 39–87%) were
reproductionispermittedwhichdoes
notcomplywiththeseterms. men. Meta-regression analysis indicated that men and younger populations
hadahigherriskofmyocarditis.Aslowdeclineintheratesofmyocarditiswas
observedasafunctionoftimefromvaccination.Theriskofbiaswaslow.
Conclusion: In this systematic review and meta-analysis, we found that the
riskofmyocarditisismorethansevenfoldhigherinpersonswhowereinfected
withtheSARS-CoV-2thaninthosewhoreceivedthevaccine.Thesefindings
support the continued use of mRNA COVID-19 vaccines among all eligible
personsperCDCandWHOrecommendations.
KEYWORDS
myocarditis,SARS-CoV-2,COVID-19vaccines,globalhealth,cardiovascularmedicine
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Voletietal. 10.3389/fcvm.2022.951314
Introduction
Participants: Persons of all ages and sex included in studies
that reported cardiac complications in either COVID-19
Thesevereacuterespiratorysyndromecoronavirus2(SARS- vaccinesorduetoCOVID-19infectiongroup.
CoV-2) is a strain that causes COVID-19. As of 15 May Intervention/Exposure:1)COVID-19vaccinesand2)SARS-
2022,morethan520millionCOVID-19cases and6.3million CoV-2infection.
deathswerereportedglobally(1).Tocombatthehighburden Comparison: 1) Non-vaccinated group and 2) Individuals
of COVID-19, vaccines were introduced to reduce the risk withoutinfection.
of severe illness and deaths (2). Although the vaccines have Outcomeofinterest:Myocarditis.
proven to reduce severe COVID-19, cardiac complications, Study type: Randomized clinical trials (RCT) and
particularly myocarditis and pericarditis, have been associated observationalstudies.
withmRNACOVID-19vaccination(3–5).Ontheotherhand,
Pairsofindependentinvestigators(NVandSPR)screenedthe
myocarditis is also one of the complications of SARS-CoV-
titles and abstracts of all citations. Studies included by either
2 infection (3, 6). However, the relative risk of myocarditis
reviewer were retrieved for full-text screening. Independent
due to vaccines and infections is not well characterized. In
investigators (NV and SPR) screened the full-text version of
severe form, myocarditis can result in chronic heart failure
eligible studies. Disagreements in the included papers were
or death, which are important safety concerns. Given the
resolvedbydiscussionandifnecessary,athirdinvestigator(PS)
high rate of vaccine hesitancy due to the fear of vaccine-
wasconsulted.
induced serious adverse events such as cardiac complications,
it is critical to characterize the relative risk of vaccine- and
infection-induced myocarditis in the general population and
Data extraction and quality assessment
determine the effect of sex and age on the risk. In this
systematicreviewandmeta-analysis,weestimatetheincidence
Astandardizeddataextractionformwasdeveloped,andtwo
of myocarditis due to SARS-CoV-2 infection vs. COVID-
investigators (NV and SPR) worked independently to extract
19vaccination.
studydetails.Thefollowinginformationwasextracted:yearof
studypublication,country,studydesign,study-leveldescriptive
Methods statistics(mean(SD)/median(IQR)ageinyears,andproportion
(%)ofwomenandmen),median/meanfollow-up,thetypeof
Results were reported following Preferred Reporting vaccine, numbers of myocarditis cases following infection and
Items for Systematic Reviews and Meta-analyses (PRISMA) vaccines, the relative risk of myocarditis. The risk of bias was
2020(7). evaluatedattheoutcomelevelusingtheCochraneCollaboration
tool for RCTs and Newcastle-Ottawa Scale for observational
studies (9, 10). Observational studies with fewer than 5 stars
Data sources and searches were considered low quality (high risk of bias); 5 to 7 stars,
moderate quality (some concerns); more than 7 stars, high
Databases such as the MEDLINE, Scopus, Cochrane quality(lowriskofbias).RCTs’riskofbiaswascategorizedas
Central Register of Controlled Trials, Cochrane Database of low,orsomeconcerns.
SystematicReviews,theWHOGlobalLiteratureonCoronavirus
Disease, and CoronaCentral were searched from December
2019 to May 2022, without language restriction. Clinical trial Data synthesis and analysis
registries and conference proceedings were also searched. The
followingMedicalSubjectHeadingsandkeywordsearchterms StatisticalanalyseswereperformedwithRsoftwareversion
were used; [“myocarditis” OR cardiac complications ] AND 3.6.2 (R Project for Statistical Computing). The Meta and
[“SARS-CoV-2” OR “Covid-19” OR “severe acute respiratory MetaforRpackageswereusedtoconductformalmeta-analyses
syndrome coronavirus-2” OR “coronavirus disease 2019”] and create forest plots. Descriptive statistics were used to
AND“vaccines”. summarizestudy-leveldemographics.
The primary outcome was the myocarditis risk due to
the vaccines and SARS-CoV-2 infection. Effect sizes were log-
Study selection transformed to normalize the distributions. Standard errors
(SEs)werecalculatedviathefollowingequations(11):Lower=
Studies were selected according to Participant (P) log(lower95%CI)andupper=log(upper95%CI),andSE=
Intervention/Exposure (I/E) Comparator [C], Outcome (upper-lower)/3.92.Todeterminetheeffectofsexandageonthe
(O)Studytype(S)[PI(E)COS]criteria(8): ratesofmyocarditis,weconductedaunivariatemeta-regression
FrontiersinCardiovascularMedicine 02 frontiersin.org
Voletietal. 10.3389/fcvm.2022.951314
analysiswiththemean(ormedian)ageofeachstudyandthe studies conducted in eight countries and three WHO regions.
proportionofmeninthestudyasregressors. Thebaselinecharacteristicsofthestudiesincludedinthemeta-
The pooled RR estimates for myocarditis risk from analysis are presented in Table1. Included studies consisted
each study were weighted by the inverse of their variances of 58 million persons, with 55.5 million in the vaccination
(inter-study plus intra-study variances). The DerSimonian cohortand2.5millionintheinfectioncohort(Table1).Overall,
and Laird’s (DL) random-effects method was used to median age was 49 years (interquartile range (IQR): 38–56),
estimate the pooled inter-study variance (heterogeneity) and 49% (IQR: 43–52%) were men. Then, 10 studies were
(12). Heterogeneity between studies was evaluated with the I2 assessed for myocarditis rates from infection and 12 studies
indicatorexpressedaspercentlow(25%),moderate(50%),and fromCOVID-19vaccines.Ofthevaccinestudies,eightassessed
high(75%)(13). mRNA vaccines (Pfizer and Moderna), one study Novavax,
Publication bias was quantitatively evaluated with Egger’s one study adenovirus vectors (AstraZeneca), and one study
linearregressionandBegg’sranktest(14,15)andqualitatively combined mRNA and J and J vaccine. Of patients diagnosed
with funnel plots. Trim and fill analyses using Duval and with myocarditis (in both vaccination and COVID-19 cohort)
Tweedie’s non-parametric method were used to adjust for 1.07% were hospitalized and 0.015% died. Of patients who
the publication bias (16). Two-sided p < 0.05 was deemed developedmyocarditisafterreceivingthevaccineorhavingthe
statisticallysignificant. infection,61%(IQR:39–87%)weremen.Ofpatientsdiagnosed
with myocarditis (in both vaccination and COVID-19 cohort)
Results 1.07%werehospitalizedand0.015%died.Themedianfollow-
up time from infection or vaccine to myocarditis was 28 days
Identified studies (IQR:28–30days).Themedianstudyqualityscoreamongthe
observational studies was 8 (range: 7–9) and was deemed as
The study selection process is shown in Figure1. A total having a low risk of bias. Similarly, RCTs also had a low risk
of763studieswerescreened.Theexclusionprocessyielded22 ofbias.
FIGURE1
PRISMAflowdiagramforstudyselection.
FrontiersinCardiovascularMedicine 03 frontiersin.org
TABLE1 Studylevelcharacteristics.
F V
ron References PublicationCountry Cohort Riskof Age,y Male Male(% Vaccine Sample Follow-up Myocar- Myocarditis Male(% Hospita- Deaths(n) ole
tiersinC year bias (mean) to(t%al) mdyioticsa)r- type size (day) ditis(n) diagnostics mdyioticsa)r- l(inz)ation tietal.
a
rd
io
va Mevorachetal. 2021 Israel Vaccine Low 49 91 Pfizer 5000000 30 136 Clinical(Brighton 91 114 1
s
c
u (17) classification)
la
rM Witbergetal.(4) 2021 Israel Vaccine Low 44 49 94 Pfizer 2500000 42 54 Clinical(CDC 94 1 1
e
d definition)
ic
in Bardaetal.(18) 2021 Israel Vaccine Low 38 52 91 Pfizer 884828 42 21 Clinical(CHS 91
e
billingcriteria)
Walteretal.(19) 2022 US Vaccine Low 8 52 0 Pfizer 1518 7 0 N/A 0 0 0
ElSahlyetal.(20) 2021 US Vaccine Low 51 53 0 Moderna 14287 14 0 N/A 0 0 0
Heathetal.(21) 2021 UK Vaccine Low 56 52 Novavax 7569 28 0 Clinical 1 0
Alietal.(22) 2021 US Vaccine Low 14 52 0 Moderna 2489 83 1 N/A 0 0 0
Dunkleetal.(23) 2022 US/Mexico Vaccine Low 47 52 0 Novavax 19714 90 0 N/A 0 0 0
Diazetal.(24) 2022 US Vaccine Low 57 41 75 Pfizer/ 2000287 20 Abnormaltroponin 75 19 0
Moderna/J&J orCMR*evidence
Simoneetal.etal. 2021 US Vaccine Low 49 46 100 Pfizer/ 2392924 10 15 Clinical/Diagnosis 100 0 0
(25) Moderna code
04 Husbyetal.(26) 2022 Denmark Vaccine Low 73 Pfizer 3482295 28 48 Clinicaldiagnosis+ 73 28 1
troponinelevation
+hospitalization
for>24hours
Husbyetal.(26) 2022 Denmark Vaccine Low Moderna 498814 28 21 Clinicaldiagnosis+ 8 0
troponinelevation
+hospitalization
for>24hours
Patoneetal.(3) 2022 UK Vaccine Low 55 35 100 AstraZeneca 20615911 28 226 Hospitaladmission 100
codes
Patoneetal.(3) 2022 UK Vaccine Low 56 33 Pfizer 16993389 28 158 Hospitaladmission
codes
Patoneetal.(3) 2022 UK Vaccine Low 40 26 Moderna 1006191 28 9 Hospitaladmission
1
codes 0
.3
Huangetal.(27) 2020 China SARS-CoV-2 Some 38 38 38 26 50 15 CMR 38 38
9
Infection concerns /fc
v
fro Laganaetal.(28) 2021 Italy SARS-CoV-2 Some 71 48 42 1169 12 Clinical=1criteria 42 1169 3 m.2
ntiersin Infection concerns fgruoimdelEinSCes 022.951
.o 3
rg (Continued) 14
F V
ron ole
tiersinC TABLE1 Continued tietal.
a
rd References PublicationCountry Cohort Riskof Age,y Male Male(% Vaccine Sample Follow-up Myocar- Myocarditis Male(% Hospita- Deaths(n)
io
v year bias (mean) (% myocar- type size (day) ditis(n) diagnostics myocar- lization
a
s
cu total) ditis) ditis) (n)
la
r
M
ed Boehmeretal.(6) 2021 US SARS-CoV-2 Low 54 59 42 1452773 30 5,069 N/A 42
ic
in Infection
e
Murketal.(29) 2020 US SARS-CoV-2 Low 65 43 70288 30 Diagnosiscode
Infection
Kunaletal.(30) 2020 India SARS-CoV-2 Low 51 65 50 108 7 3 Definitediagnosis 50 1
Infection withbiopsy,
probablydiagnosis
withclinical
characteristicswith
eithertroponin
elevation,
myocardialinjury,
0
5 orECGchanges
suggestiveofinjury
Dengetal.(31) 2020 China SARS-CoV-2 Low 65 51 71 112 66 14 AHAguideline: 71 112 13
Infection tripleelevationin
troponinwitheither
ECGchangesor
echocardiographic
changes
Danielsetal.(32) 2021 US SARS-CoV-2 Low 67 73 2810 77 37 CMR 73 0
Infection
Martinezetal. 2021 US SARS-CoV-2 Some 25 99 789 19 3 CMR 0 0
(33) Infection concerns
Buckleyetal.(34) 2021 US SARS-CoV-2 Low 48 43 44 718365 35,820 N/A 44
1
0
Infection .3
3
Bardaetal.(18) 2021 Israel SARS-CoV-2 Low 34 46 233392 93,812 N/A:diagnosiscode 89
Infection /fcv
m
fro .2
ntiersin *CMR=CardiacMagneticResonanceImaging;J&J,JohnsonandJohnson. 022.951
.o 3
rg 14
Voletietal. 10.3389/fcvm.2022.951314
FIGURE2
AssociationofmyocarditisafterCOVID-19vaccinationversusSARS-CoV-2infection.Theriskofmyocarditisfrominfectionwasmorethan
7-foldhigherthanvaccination.
Risk of myocarditis due to SARS-CoV-2 Meta-regression, publication bias, and
infection vs. COVID-19 vaccination study heterogeneity
The relative risk (RR) for myocarditis was more To assess the effect of sex, age, types of vaccines (mRNA
than seven times higher in the infection group than vs. non-mRNA vaccines), WHO regions, and follow-up time
vaccination group (RR: 15 (95% CI: 11.09–19.81, infection on myocarditis, we carried out a univariate meta-regression.
group) and RR: 2 (95% CI: 1.44–2.65), vaccine group, The analysis was stratified by vaccine and infection risk
Figure2). Higher rates of myocarditis were observed rates separately. In the studies that examined vaccine risk
in those who received Moderna vaccines followed by ratios, younger age was associated with the increasing risk of
Pfizer vaccines and the lowest in other vaccines groups myocarditis. Although male sex, mRNA vaccines, and studies
(Figure3). Additionally, higher rates of myocarditis conducted in the Americas were associated with an increased
were observed in studies conducted in the Americas (the risk of myocarditis, the association did not reach statistical
United States and Mexico) compared to other WHO regions significance (Table2). When vaccines and infection studies
(Figure4). werecombined,malesexandtheAmericasWHOregionwere
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Voletietal. 10.3389/fcvm.2022.951314
FIGURE3
MyocarditisafterCOVID-19vaccinationstratifiedbyvaccinetype.TheriskofmyocarditiswashighestintheModernavaccinegroup.
associated with an increased risk of myocarditis, but age and Egger’s test for publication bias was significant (p=0.01) but
follow-uptimewerenot. Begg’s test was non-significant (p = 0.14). Consequently, we
Publication bias was assessed only for the vaccine cohort conductedDuvalandTweedie’strimandfilltesttobalancethe
studies. Due to the small number of studies in the infection funnel plot and adjust for potential publication bias (16). The
cohort, we did not assess publication bias for these studies. resultsindicatedthatifpublicationbiasexisted,threeadditional
Visual inspection of a funnel plot of the included studies did studieswouldbeneededtoeliminatebias,andtheoveralleffect
indicateaslightasymmetryindicativeofmildpublicationbias. of vaccines on myocarditis would change from 2 (95% CI:
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Voletietal. 10.3389/fcvm.2022.951314
FIGURE4
MyocarditisafterCOVID-19vaccination/InfectionstratifiedbyWHOregions.TheriskofmyocarditiswashigherintheAmericas(USandMexico)
comparedtoEurope.
1.44–2.65)to1.5(95%CI:1.11–1.26,SupplementaryFigureS1). This translates into more than a 7-fold higher risk in the
To identify outlier studies, we further performed influence infection group compared to the vaccination group. Among
sensitivity analyses by excluding and replacing one study the persons with myocarditis in the vaccinated group, 61%
at a time (Leave-One-Out method) from the meta-analysis (IQR: 39–87%) were men. Younger populations demonstrated
and calculated the RR for the remaining studies (35). No anincreasedriskofmyocarditisafterreceivingtheCOVID-19
substantial change from any of the pooled RR was observed vaccination.Nevertheless,theriskofhospitalizationanddeath
when other studies were removed in turn indicating that no waslow.Thisreviewisimportantasthereismuchhesitancyin
individual study had a considerable influence on the pooled thegeneralpopulationofreceivingtheCOVID-19vaccinegiven
estimate. The plots for the analysis estimates are provided in itsseriousadverseeffects.
SupplementaryFigureS2. OurfindingsareconsistentwiththerecentanalysisofEHR
datafrom40U.S.healthcaresystemswhichfoundtheincidences
ofcardiaccomplicationsafterSARS-CoV-2infectionofnearly7-
Discussion foldhigherthanaftermRNACOVID-19vaccination(36).The
risk was higher for both men and women in all age groups.
This is the first systematic review and meta-analysis and In a Danish population study, vaccination with mRNA-1273
the largest study to date of acute myocarditis after SARS- wasassociatedwithasignificantlyincreasedriskofmyocarditis,
CoV-2 vaccination or infection that estimate the risk ratio primarily driven by an increased risk among individuals aged
of myocarditis due to SARS-CoV-2 infection vs. COVID-19 12–39years(26).Nevertheless,theabsoluterateofmyocarditis
vaccination.Wefoundthattheriskofmyocarditisincreasedby or myopericarditis after SARS-CoV-2 mRNA vaccination was
afactorof2and15aftervaccinationandinfection,respectively. low,eveninyoungeragegroups.
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Voletietal. 10.3389/fcvm.2022.951314
TABLE2 Resultsofmeta-regressionanalyses. biopsies. Only two studies included three patients who
underwentendomyocardialbiopsywithnodiagnosticevidence
Cohorts Covariate Nstudies RR p- R2
of myocarditis on biopsy (4, 17). Another limitation is a wide
(95%CI) value(%)
variationinthefollow-uptime(range7–90days)whichmight
have counfounded the risk estimate. Lastly, although studies
Onlyvaccine %male(per 6 1.15(0.96to1.37) 0.13 40
from multiple countries were included, most of the patient
studies 5%-pointincrease
populationwerefromtheUSortheUKregion.Therefore,the
inpropmale)
findings may not be generalizable to other geographic regions
Age(per5-year 5 0.74(0.61to0.89) 0.002 100
notstudiedsuchasAfrica.
increase)
Follow-up(per7-d 8 0.97(0.71to1.13) 0.87 0.0
increasefrom Conclusion
vaccination)
mRNAvaccinesvs. 8 1.70(0.67to4.31) 0.26 0.0
Inthissystematicreviewandmeta-analysis,wefoundthat
other
theriskofincidentmyocarditisismorethanseventimeshigher
Americas 7 1.45(0.56to3.75) 0.44 6.0
Vaccinesand %male(per 9 1.38(1.14to1.68)0.0009 89 in persons who were infected with the SARS-CoV-2 than in
infection 5%-pointincrease those who received the COVID-19 vaccines. These findings
studies inpropmale) supportthecontinueduseofmRNACOVID-19vaccinesamong
Age(per5-y 8 0.98(0.88to1.10) 0.76 0 alleligiblepersonspertheCDCandWHOrecommendations.
increase)
Follow-up(per7-d 10 1.11(0.45to2.74) 0.82 6
Data availability statement
increasefrom
vaccination)
Americasvs.other 11 2.94(1.17to7.44) 0.02 82 The original contributions presented in the study are
WHOregions includedinthearticle/Supplementarymaterial.Rcodeanddata
toreproducetheresultsinthisarticlearearchivedatGitHub.
Boldvaluesarestatisticallysignificant.R2:Coefficientofdeterminationrepresentsthe
The link to GitHub is: https://github.com/ssentongojeddy/
amountofvariationintheriskofmyocarditisexplainedbythecovariateinthemeta-
regressionmodel. Myocarditis_COVID19.Furtherinquiriescanbedirectedtothe
correspondingauthor.
Myocarditiscanbeself-limiting,butsomecasescanadvance
to life-threatening conditions with associated heart failure, Ethics statement
arrhythmias,ormyocardialinfarction.Thepathophysiologyof
myocarditisinCOVID-19infectionisthoughttoberelatedto
Ethical review and approval was not required for
directviralinjurytothecardiacmyocytes,butitisalsoproposed
this study in accordance with the local legislation and
that there may be a component of cytokine storm syndrome
institutionalrequirements.
(37). Similarly, mechanisms of myocarditis associated with
COVID-19 vaccines include but are not limited to molecular
mimicry, autoantibody formation, mRNA immune reactivity, Author contributions
trigger of preexisting dysregulated immune processes, and
geneticpredisposition(38). PS and NV: study concept and design, methodology,
Our study have several strengths. First, we studied a large supervision, interpretation of data, and drafting of the
sample size of 58 million individuals. Additionally, various manuscript. SR: data collection. PS: statistical analysis. All
vaccinetypeswereincludedinthismeta-analysis,whichallows authors critically revised the manuscript for important
for generalizability of the relationship between COVID-19 intellectual content and approved the final version of
vaccination and myocarditis. Third, due to the high degree themanuscript.
of heterogeneity, a random effects meta-analytic framework
wasinvoked.
Funding
Thefindingsofthismeta-analysisshouldbeinterpretedin
lightofsomelimitations.First,studiesvariedintheirmethods
of diagnosing myocarditis: Although myocarditis is suspected Penn State College of Medicine Startup Funds to PS. The
by clinical diagnosis, cardiac biomarkers and ECG changes, funder had no role in the design and conduct of the study;
confirmationismadebyperforminganendomyocardialbiopsy collection,management,analysis,andinterpretationofthedata,
or with a Cardiac MRI (CMR). However, not all medical preparation,review,orapprovalofthemanuscript,anddecision
centers had the facilities to perform CMR or endomyocardial tosubmitthemanuscriptforpublication.
FrontiersinCardiovascularMedicine 09 frontiersin.org
Voletietal. 10.3389/fcvm.2022.951314
Conflict of interest
the editors and the reviewers. Any product that may be
evaluated in this article, or claim that may be made
Theauthorsdeclarethattheresearchwasconductedinthe by its manufacturer, is not guaranteed or endorsed by
absenceofanycommercialorfinancialrelationshipsthatcould thepublisher.
beconstruedasapotentialconflictofinterest.
Publisher’s note Supplementary material
All claims expressed in this article are solely those The Supplementary Material for this article can be
of the authors and do not necessarily represent those found online at: https://www.frontiersin.org/articles/10.3389/
of their affiliated organizations, or those of the publisher, fcvm.2022.951314/full#supplementary-material
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