key: cord-0427435-ks0zkp57
authors: Chouchana, L.; Blet, A.; Al-Khalaf, M.; Kafil, T. S.; Nair, G.; Robblee, J.; Drici, M.-D.; Valnet-Rabier, M.-B.; Micallef, J.; Salvo, F.; Treluyer, J.-M.; Liu, P.
title: Cardiac Inflammation after COVID-19 mRNA Vaccines: A Global Pharmacovigilance Analysis
date: 2021-08-18
journal: nan
DOI: 10.1101/2021.08.12.21261955
sha: b813f867e7649fd87deb24fcdbcf7c96b5c82c3a
doc_id: 427435
cord_uid: ks0zkp57

Background To counter the COVID-19 pandemic, mRNA vaccines, namely tozinameran and elasomeran, have been authorized in several countries. These next generation vaccines have shown high efficacy against COVID-19 and demonstrated a favorable safety profile. As widespread vaccinations efforts are taking place, incidents of myocarditis and pericarditis cases following vaccination have been reported. This safety signal has been recently confirmed by the European Medicine Agency and the U.S. Food and Drug Administration. This study aimed to investigate and analyze this safety signal using a dual pharmacovigilance database analysis. Methods This is as an observational study of reports of inflammatory heart reactions associated with mRNA COVID-19 vaccines reported in the World Health Organization's global individual case safety report database (up to June 30th 2021), and in the U.S. Vaccine Adverse Event Reporting System (VAERS, up to May 21st 2021). Cases were described, and disproportionality analyses using reporting odds-ratios (ROR) and their 95% confidence interval (95%CI) were performed to assess relative risk of reporting according to patient sex and age. Results At a global scale, the inflammatory heart reactions most frequently reported were myocarditis (1241, 55%) and pericarditis (851, 37%), the majority requiring hospitalization (n=796 (64%)). Overall, patients were young (median age 33 [21-54] years). The main age group was 18-29 years old (704, 31%), and mostly males (1555, 68%). Pericarditis onset was delayed compared to myocarditis with a median time to onset of 8 [3-21] vs. 3 [2-6] days, respectively (p=0.001). Regarding myocarditis, an important disproportionate reporting in males (ROR, 9.4 [8.3-10.6]) as well as in adolescents (ROR, 22.3 [19.2-25.9]) and 18-29 years old (ROR, 6.6 [5.9-7.5]) compared to older patients were observed. Conclusions The inflammatory heart reactions, namely myocarditis and pericarditis, have been reported world-wide shortly following COVID-19 mRNA vaccination. An important disproportionate reporting among adolescents and young adults, particularly in males, was observed especially for myocarditis. Guidelines must take this specific risk into account and to optimize vaccination protocols according to sex and age. While the substantial benefits of COVID-19 vaccination still prevail over risks, clinicians and the public should be aware of these reactions and seek appropriate medical attention.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

Myocarditis and pericarditis are inflammatory heart conditions that occur in the setting of 91 excessive host immune response to antigenic stimuli, and have diverse outcomes ranging from 92 mild to severe. 1 They usually occur after viral infections or other stimuli that induce immune 93 system activation. 2 Recently, viral myocarditis has been widely reported after SARS-CoV-2 94 infection and subsequent development of coronavirus disease . 3, 4 In some instances, 95 these inflammatory reactions have been associated with some drug exposure, such anticancer 96 agents, clozapine or vaccines. 5-7 A descriptive analysis of drug associated myopericarditis 97 spontaneous reports in the United States (1990 States ( -2018 identified that about 0.1% of the cases 98 were related to vaccines. 8 To date, inflammatory cardiac reactions following vaccination have 99 been mostly reported with live-virus vaccines, such as the smallpox vaccine, 6,9,10 and inactivated 100 influenza vaccines, 11 Cases reports of myocarditis/pericarditis secondary to next-generation 101 vaccine platforms, used to prevent COVID-19, have been reported. 12-17 102 Vaccination is critical to contain the SARS-CoV-2 pandemic. Messenger RNA (mRNA) 103 vaccines, which have been produced experimentally during the Zika virus outbreak, represent a 104 new generation of vaccines that can be rapidly responsive to emerging viruses, such as SARS-105

CoV-2. 18 Pivotal phase 3 randomized clinical trials were conducted on 71,265 volunteers, 106 including 35,654 who were exposed to the active mRNA vaccines. 19 ,20 Up to July 2021, 107 tozinameran (BNT162b2 mRNA, Pfizer-BioNTech) and elasomeran (mRNA 1273, Moderna) 108 have been distributed in 104 and 49 countries worldwide, respectively, and more than 341 million 109 doses have been administered in the U.S. 21 While these vaccines appear to have a particularly 110 good safety profile, special attention must be paid to potential adverse effects due to their 111 novelty. Rare but severe adverse drug reactions have been highlighted in clinical trials and 112 thereafter reported after COVID-19 mRNA vaccination, such as anaphylaxis or Bell's palsy. 22-24 113 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint

Recently, a growing signal concerning inflammatory heart reactions, which has not been pointed 114 out during clinical trials, has emerged in several regions of the world, including Israel, Europa 115 and the U.S., with early coverage in the press. 25-27 A small case series in members of the U.S. 116

Military suggested an incidence below one over 100,000 doses administered. 14 Preliminary 117 analysis by national authorities led to confirm this safety signal and a probable causal relationship 118 in Europe and in the U.S. 28,29 119 In this study, we aim to document the inflammatory heart reactions reported after 120 COVID-19 mRNA vaccination and further analyze this safety signal using a dual 121 pharmacovigilance database analysis based on the World Health Organization's (WHO) global 122

Individual Case Safety Report database (VigiBase) and the U.S. Vaccine Adverse Event 123

Reporting System (VAERS). The aims of the study are: 1) to describe these cases and their 124 relevant clinical features, and 2) to perform disproportionality analyses to evaluate a potential 125 association of inflammatory heart reactions reporting after mRNA COVID- All of the data used for analysis were de-identified, and only aggregate data are reported. 159 160 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint

Reports including a COVID-19 mRNA vaccine (tozinameran or elasomeran) as the 162 suspected drug in the adverse reaction have been extracted from both databases. From that, cases 163 of inflammatory heart reactions, i.e. myocarditis, myopericarditis, pericarditis, and 164 pleuropericarditis, were retrieved using the ad-hoc high-level terms from MedDRA, "non 165 infectious myocarditis" and "non infectious pericarditis", coded as reactions. Cases included in 166 this study were registered up to May 21 st and June 30 th 2021, in VAERS and in VigiBase, 167 respectively. 168

In VigiBase, for each report of interest, the following data were extracted or assessed: 169 demographic features, continent of reporting, type of reporter, month of reporting, patient sex, 170 patient age, time to reaction onset, seriousness, reaction outcome and type of heart inflammatory 171 reaction Serious cases were defined, according to the WHO, as the occurrence of death, life-172 threatening adverse event, inpatient hospitalisation or prolongation of an existing hospitalisation, 173 significant disability or requirement of intervention to prevent any of these. 174

In VAERS, for each report of interest, the following data were extracted or assessed: 175 vaccine type, type of heart inflammatory reaction, patient age, sex, COVID-19 prior to 176 vaccination, reaction occurrence after the 1 st or 2 nd dose of vaccine, onset of the symptoms, type 177 of symptoms, biological and radiological exams, complications, treatment, and hospitalization. 178

Duplicates in VAERS were removed when identified from the short narrative. 179 180

Disproportionality analyses, also called case -non-case studies are similar to case -control 182 studies but for purpose of pharmacovigilance studies. These studies are nested in a database of 183 spontaneous reports to assess possible disproportionality in reporting. Disproportionality analysis 184 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint compares the proportion of a specific adverse drug reaction reported in a specific group (e.g. drug 185 exposure, patient age, patient sex) with the proportion of the same adverse drug reaction for a 186 control group. [34] [35] [36] This statistical approach has shown its value to assess relative risks of adverse 187 drug reaction, that are correlated in most cases with results from meta-analyses of clinical trials. 37 188

To assess an association between inflammatory heart reactions after mRNA vaccines and patient 189 age or sex, we performed a disproportionality analysis among different patient groups. 190

Characteristics of interest are patient sex and age groups, specially 12-17 years, 18-29 years and 191 over 30 years, as reported by safety signals of concern. Cases are reports concerning a specific 192 patient group and that include the terms myocarditis, pericarditis or pleuropericarditis as reactions 193 after a COVID-19 mRNA vaccine. Non-cases are reports concerning a specific patient group and 194 that include all other reactions to a COVID-19 mRNA vaccine. Therefore, our analyses assessed 195 a potential difference of reporting of inflammatory heart reactions secondary to mRNA vaccines in male compared to female and in 12-17 years or 18-29 years old patients 197 compared to patients over 30 years old. Thereafter, sensitivity analyses were performed, 198 restricted to serious reports only, and to reports originating from a healthcare professional. 199

Descriptive analysis was performed on the cases retrieved from the two databases. Quantitative 202 variables were expressed as median ± interquartile range (IQR) and compared using non-203 parametric analysis. Qualitative variables were expressed in number and percentages. Time to 204 reaction onset was analyzed using a survival Mantel-Cox model. 205

Disproportionality in reporting between groups is expressed using reporting odds ratio (ROR) 206 and its 95% confidence interval (95% CI). ROR is a ratio similar in concept to the odds ratio in 207 case -control studies and corresponds to the exposure odds among reported cases of interest over 208 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Table 1) . The inflammatory heart reactions most 225 commonly reported were myocarditis (1241, 54.5%) and pericarditis (851, 37.4%). Patients were 226 of the younger age bracket (median age 33 [21-54]) mostly from the group between 18-29 year-227 old (704, 30.9%), more commonly males (1555 (68.3%). Patient distribution was different 228 according to age and sex (p<0.0001) for both myocarditis and pericarditis (Figure 1) . 229

Specifically, most of myocarditis cases have been reported in 12-17 and 18-29 years old males. 230

Myocarditis cases originating from the U.S. were mainly reported after May 2021, although 231 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint reactions occur alongside with vaccination achievements (Figure 2A recipients compared with recipients over 30 years old. Specifically, this increased reporting was 250 more marked in males than in females, among all age groups ( Figure 4A ). Regarding 251 pericarditis, a disproportionate reporting in males among all age groups, compared to females 252 was observed ( Figure 4B ). Younger males belonging to 12-17 and 18-29 years old groups were 253 also more prone to pericarditis reporting after COVID-19 mRNA vaccines compared to over 30 254 years old group. This finding not being true in females in whom no disproportionality in 255 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. In this global pharmacovigilance retrospective observational study, we report here the 285 largest case series to date on the clinical features of inflammatory heart reactions, myocarditis 286 and pericarditis, following COVID-19 mRNA vaccine immunization. These cases mostly 287 required hospitalization and some were life threatening, and occasionally fatal. Fatal cases 288 occurred in about 1% of the patients, mostly older. Although our analysis cannot assess real 289 incidence, these inflammatory heart reactions representing 31.8 per 10,000 of COVID-19 mRNA 290 vaccine reports appeared to be rare. Regarding myocarditis, our global data show that they were 291 highly likely to be reported in adolescents and young adults below 30 years old. Males has a high 292 disproportionate reporting risk compared to females. 293

Overall clinical features from these databases are also consistent with the experience 294 reported by the Israeli investigators. They have identified 110 myocarditis cases amongst their 5 295 million population who received 2 doses of the tozinameran vaccine. 14 This translates to 296 approximately 1 in 50,000 vaccine recipients, noting however the rates in young males were 5 to 297 25 times higher than expected. The investigators also observed a higher rate of incidence 298 following the second dose, as well as 2 deaths in the cohort which may or may not be causally 299 related. This overall pattern is consistent with features of traditional viral myocarditis, which 300 occurs more commonly in younger male patients. Noteworthy, Israel's spontaneous reports are 301 not transmitted to VigiBase. Israel has been a leader in the current global mass immunization 302 effort, due to the achievements of the campaign, a larger proportion of young people have been 303 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint vaccinated compared to other countries using mRNA vaccines. The CDC reported that 304 myocarditis reactions after vaccination with tozinameran vaccine were reported by adolescents 305 aged 12-17 years to U.S. vaccine safety monitoring systems. 37 306

Myocarditis and pericarditis have been previously reported after vaccinations. 8 The most 307 well studied example is that following smallpox vaccine, which in the relatively heathy U.S. 308 military personnel had an incidence of myocarditis of 1 in 12,819 individuals. 38 The complication 309 rate was significantly decreased when the vaccine dose was subsequently reduced, suggesting a 310 causal relationship, but it featured a live attenuated virus. Inflammatory cardiac reactions after 311 inactivated virus vaccines such as influenza vaccines are also known to occur, but are generally 312 considered as rare events, mainly occurring in young adults. 8 313

Following the widespread adoption of community-based mitigation measures to reduce 314 the transmission of SARS-CoV-2, the percentage of other respiratory diseases, such as influenza 315 infection, has declined to historically low levels. 39,40 Therefore, we can hypothesize that the 316 background risk for myocarditis is probably lower than usual. In this present study, distribution 317 of myocarditis/pericarditis by sex and age was similar to previous cases described for other 318 vaccines: mostly young adult males. 8 Potential mechanisms for these observed reactions are 319 currently unknown, but several hypotheses may be considered. The first is that incidence appears 320 to be higher in situations related to higher immune reactivity (younger patient population, after 321 second dose, etc.). This may be related to greater adaptive immune response in younger 322 individuals, which in turn may lead to greater increases of CD4+ Th17+ cell populations, which 323 predisposes individuals to developing myocarditis. It will be interesting to see if the recently 324 reported microRNA diagnostic of Th17 activation in myocarditis is also positive in these 325 patients. 41 Second is the possibility that mRNA in these vaccines may enhance autoimmunity. 42 326 mRNA is known to be a self-adjuvant for innate immune responses, and this may help to explain 327 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CoV-2 has not been found in cardiomyocytes, but only in the remaining myocardium, thus the 341 cell injury was thought to be due to the generalized inflammatory response to COVID-19, part of 342 which is Th1 activation. 45 Hence in COVID-19 mRNA vaccine associated myocarditis, it appears 343 unlikely that the translation of large amount of SARS-CoV-2 spike proteins through the vaccines 344 may also engage the ACE2 and related receptors and play a role in reaction onset. 345 346 This retrospective pharmacovigilance analysis has some limitations and strengths. 347

VigiBase and VAERS are based on spontaneous reports. Anyone can submit a report, including 348 parents and patients, which are analyzed and documented by national or regional 349 pharmacovigilance centers. Spontaneous reports will likely feature under-reporting of total real 350 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint world cases and variable data quality, all of which are inherent to any pharmacovigilance system. 351 46 

For instance, previous prospective study of the incidence of myocarditis/pericarditis following 353 smallpox and influenza vaccination suggested significant underestimation of true incidence of 354 these complications with passive surveillance alone. 47 Hence, one major limitation of 355 spontaneous reporting is that it is not possible to assess incidence of inflammatory heart reactions 356 following COVID-19 vaccination and total number of cases is highly underestimated. However, 357

VigiBase, covering more than 90% of the world's population, provides a unique opportunity to 358 analyze rare adverse events at a global scale. Furthermore, although we cannot eliminate residual 359 confounders, disproportionality analysis on VigiBase has proven its value in detecting safety 360 signal or increased risk of events. 34 We first report a global analysis on inflammatory cardiac reactions such as 373 myocarditis/pericarditis occurring after COVID-19 mRNA vaccine. Compared to hundreds of 374 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint millions of doses administered worldwide, these complications appeared to be rarely reported, 375 although most of them required hospitalization. Reporting risk of myocarditis is highly increased 376 in adolescents or young adults, and in males. Absolute risk may greatly increase with the 377 achievements of the mass immunization campaign and the enlargement of vaccination to young 378 adults. COVID-19 mRNA vaccine causality has been established by national authorities; further 379 data will be needed to analyze this safety signal. Meanwhile, recommendations should be 380 communicated to manage mass immunization in young adults and children, especially males. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint

VigiBase is a fully deidentified database maintained by the Uppsala Monitoring Center (UMC). 397

The authors are indebted to the National Pharmacovigilance centres that contributed data. 398

Information from VigiBase comes from a variety of sources, and the probability that the 399 suspected adverse effect is drug-related is not the same in all cases. The information does not 400 represent the opinion of the Uppsala Monitoring Center (UMC) or the World Health Organization 401 and only reflects the authors' opinion. 402

According to VigiBase access rules, no specific ethical approval is needed. VigiBase access is 403 granted to national and regional pharmacovigilance centers such our teams. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Case-non-case approach is similar to case-control method but for the purposes of 620 pharmacovigilance studies. Disproportionality in adverse drug reaction reporting between groups 621 is expressed using reporting odds ratios (ROR) and their 95% confidence interval (95% CI). ROR 622 is a ratio similar in concept to the odds ratio in case-control studies and corresponds to the 623 exposure odds among reported cases of inflammatory cardiac disorders over the exposure odds 624 among reported non-cases. An ROR over 1.0 suggests that inflammatory cardiac disorders are 625 more frequently reported in COVID-19 mRNA vaccine recipients specific group compared with 626 control group. We performed the main analysis and a secondary analysis stratified to age groups. The typical journey of patient experienced a myocarditis following an mRNACOVID-19 vaccine 635 is described. Starting at day 0 after receiving 1 st or 2 nd dose of vaccine. Appearance of systemic 636 reactogenicity symptoms at day 1, followed by chest pain and shortness of breath (SOB) at day 3, 637 leading to consultation at the Emergency Room (ER), and hospitalization for a median of 2 days. 638 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 18, 2021. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 18, 2021. ; https://doi.org/10.1101/2021.08.12.21261955 doi: medRxiv preprint 

Role of innate and adaptive immune mechanisms in cardiac 421 injury and repair

Report of the 1995 World Health 424

Organization/International Society and Federation of Cardiology Task Force on the 425 Definition and Classification of cardiomyopathies

Prospective Case-Control Study of Cardiovascular 431 Abnormalities 6 Months Following Mild COVID-19 in Healthcare Workers

Big 437 Ten COVID-19 Cardiac Registry Investigators

Myocarditis in Competitive Athletes With Recent SARS-CoV-2 Infection: Results From the 439 Big Ten COVID-19 Cardiac Registry

Immune checkpoint inhibitors-related myocarditis 441 in patients with cancer: an analysis of international spontaneous reporting systems

Engler 445 RJM, Department of Defense Smallpox Vaccination Clinical Evaluation Team. Incidence 446 and follow-up of inflammatory cardiac complications after smallpox vaccination

Clozapine-Associated Myocarditis: A 449 Protocol for Monitoring Upon Clozapine Initiation and Recommendations for How to 450 Conduct a Clozapine Rechallenge

Myocarditis Following 471 Immunization With mRNA COVID-19 Vaccines in Members of the US Military

Borgeson 475 DD. Myocarditis After BNT162b2 and mRNA-1273 Vaccination

Myocarditis with COVID-19 mRNA Vaccines

Use of mRNA COVID-19

Vaccine After Reports of Myocarditis Among Vaccine Recipients: Update from the 483

Advisory Committee on Immunization Practices -United States

The promise of mRNA 486 vaccines: a biotech and industrial perspective

Efficacy and Safety 492 of the mRNA-1273 SARS-CoV-2 Vaccine

Surveillance for safety after immunization: 532 Vaccine Adverse Event Reporting System (VAERS)--United States

French legal approach to patient 535 consent in clinical research

Benefits and strengths of the 537 disproportionality analysis for identification of adverse drug reactions in a 538 pharmacovigilance database

Case-non-case studies: Principle, methods, bias and interpretation

Adverse drug 542 reaction risks obtained from meta-analyses and pharmacovigilance disproportionality 543 analyses are correlated in most cases

COVID-19 Vaccine Safety in 546

Adolescents Aged 12-17 Years -United States

550 Department of Defense Smallpox Vaccination Clinical Evaluation Team. Myopericarditis 551 following smallpox vaccination among vaccinia-naive US military personnel

Decreased Influenza Activity During the COVID-19 Pandemic -United States

How COVID-19 is changing the cold and flu season

A Novel Circulating 566 MicroRNA for the Detection of Acute Myocarditis

The Science Underlying COVID-19: Implications for the 568 Cardiovascular System

Chahal 570 CAA. Recognizing COVID-19-related myocarditis: The possible pathophysiology and 571 proposed guideline for diagnosis and management

The protein expression 573 profile of ACE2 in human tissues

Myocarditis in COVID-19 patients: current 575 problems

Temporal Associations 577 Between Immunization With the COVID-19 mRNA Vaccines and Myocarditis: The 578 Vaccine Safety Surveillance System Is Working

A prospective study of 582 the incidence of myocarditis/pericarditis and new onset cardiac symptoms following 583 smallpox and influenza vaccination

Causality assessment of 586 adverse events reported to the Vaccine Adverse Event Reporting System (VAERS)

Myocarditis After mRNA COVID-19 Vaccine

Management of Acute Myocarditis and Chronic Inflammatory 594