Latest Research

Cardiotoxic Impact of Covid mRNA Vaccines, Published Papers

The studies listed below are peer reviewed papers on the topic of the impact of the Covid mRNA vaccines on the cardiovascular system Please check back from time to time as this list is expanded with the release of new papers.

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mRNA-based SARS-CoV-2 vaccines: intracellular processing and aggregation of the encoded spike protein as a mechanistic contributor to cardiac cellular stress

Study Details
FULL TEXT LINK: View Paper (Download PDF)
PUBLICATION DATE: February, 2026
PUBLICATION: Frontiers
AUTHORS
Rolf Schreckenberg, Nadine Woitasky, Nadja Itani, Laureen Czech, Anita C. Windhorst, Malte Juchem, Christian Bär, Thomas Thum, Péter Ferdinandy
CORRESPONDENCE TO
rolf.schreckenberg@physiologie.med.uni-giessen.de
DOI: 10.3389/fimmu.2026.1635478
PMID: Not indexed
ABSTRACT
Introduction:
The trimeric spike (S) protein on the envelope of the SARS-CoV-2 virus is the primary target structure for currently approved corona vaccines. For this reason, the two mRNA-based corona vaccines Comirnaty (BNT162b2, Pfizer/BioNTech) and Spikevax (mRNA-1273, Moderna) first induce the production of a spike monomer in body cells. After enzymatic cleavage by the endoprotease furin, two S subunits are formed, which are supposed to trigger the desired
immune response following secretion. Based on this concept, a preventive measure against symptomatic SARS-CoV-2 infections became available within one year of the pandemic’s onset. mRNA-based vaccines have proven highly effective in reducing severe disease and mortality. However, both the virus itself and mRNA vaccines have been associated with cardiac symptoms, which are commonly classified as myocarditis, pericarditis, or a combination thereof based on clinical presentation. Although vaccine-induced myocarditis remains a rare
adverse event, recent longitudinal studies have raised questions regarding its long-term impact.
Objective:
To better understand the molecular mechanisms potentially involved in vaccine-associated cardiac side effects, we investigated the translation and proteolytic processing of the encoded spike monomers in human AC16 cardiomyocytes, as well as (for comparative purposes) in HEK-293 and HeLa cells.
Results:
In all three cell types, both BNT162b2 and mRNA-1273 produced two divergently sized monomer translation products from which one S1 subunit was formed after enzymatic cleavage. However, the number of identified S2 subunits varied between two and four depending on the cell line and mRNA used. Within a few hours, covalently bonded high-molecular complexes formed from both the spike monomers and their subunits. The arrangement of these complexes always adhered to a consistent pattern in each cell type. Particularly in AC16 cardiomyocytes, the various spike protein derivatives impaired not only cell
proliferation, but also induced a pro-inflammatory response and oxidative stress. Only the secreted S1 subunit was detected as an immunogen in the supernatant of all three cell lines.
Conclusion:
Our findings may help to improve the safety and specificity of future mRNA platform technologies by emphasizing the importance of evaluating intracellular protein processing and the potential cellular effects of translated immunogens already during preclinical development.

COVID-19 Vaccine-Induced Subclinical Myopericarditis: Pathophysiology, Diagnosis, and Clinical Management

Study Details
FULL TEXT LINK: View Paper (PDF)
PUBLICATION DATE: November, 2025
PUBLICATION: European Society of Medicine
AUTHORS
Peter A. McCullough, MD, MPH, M. Nathaniel Mead, MSc, PhD, Nicolas Hulscher, MPH
CORRESPONDENCE TO
nichulscher@gmail.com
DOI: 10.18103/mra.v13i11.7078
PMID: Not indexed
ABSTRACT
The currently approved COVID-19 mRNA boosters carry a warning for acute, clinically apparent, vaccine-induced myocarditis. This serious condition has resulted in hospitalization and, in well-documented cases, fatalities. However, there is growing concern that long-lasting synthetic mRNA and persistent production of SARS-CoV-2 Spike protein may accumulate in the heart and cause cardiotoxicity over time. Additionally, subtler cardiovascular symptoms, which may not require immediate hospitalization, can also develop. Such symptoms include atypical or pleuritic chest pain, palpitations, intermittent arrhythmias, labile blood pressure with hyper- and hypotension and effort intolerance. Areas of inflammation found at autopsy too small to be detectable by cardiac magnetic resonance imaging have been associated with sudden death. Alarmingly, the initial presentation can include cardiac arrest with no premonitory symptoms. A thorough evaluation, including history of SARS-CoV-2 infections, the number and type of mRNA COVID-19 vaccines received, quantitative Spike protein antibody levels, ECG, imaging, and laboratory tests, form the cornerstone of initial assessment. Clinical and preclinical observations suggest combined oral administration of nattokinase, bromelain, and curcumin may support detoxification of the heart and cardiovascular system from Spike protein. The addition of colchicine and other targeted therapies may be essential in reducing myocardial and systemic vascular inflammation. These approaches hold promise to risk mitigation of sudden cardiac death in immunized individuals affected by subclinical COVID-19 vaccine induced myopericarditis.

Autopsy findings in cases of fatal COVID-19 vaccine-induced myocarditis

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: October, 2025
PUBLICATION: PubMed
AUTHORS
Nicolas Hulscher, Roger Hodkinson, William Makis, Peter A McCullough
CORRESPONDENCE TO
nichulscher@gmail.com
DOI: 10.1002/ehf2.14680
PMID: 38221509
ABSTRACT
COVID-19 vaccines have been linked to myocarditis, which, in some circumstances, can be fatal. This systematic review aims to investigate potential causal links between COVID-19 vaccines and death from myocarditis using post-mortem analysis. We performed a systematic review of all published autopsy reports involving COVID-19 vaccination-induced myocarditis through 3 July 2023. All autopsy studies that include COVID-19 vaccine-induced myocarditis as a possible cause of death were included. Causality in each case was assessed by three independent physicians with cardiac pathology experience and expertise. We initially identified 1691 studies and, after screening for our inclusion criteria, included 14 papers that contained 28 autopsy cases. The cardiovascular system was the only organ system affected in 26 cases. In two cases, myocarditis was characterized as a consequence from multisystem inflammatory syndrome. The mean age of death was 44.4 years old. The mean and median number of days from last COVID-19 vaccination until death were 6.2 and 3 days, respectively. We established that all 28 deaths were most likely causally linked to COVID-19 vaccination by independent review of the clinical information presented in each paper. The temporal relationship, internal and external consistency seen among cases in this review with known COVID-19 vaccine-induced myocarditis, its pathobiological mechanisms, and related excess death, complemented with autopsy confirmation, independent adjudication, and application of the Bradford Hill criteria to the overall epidemiology of vaccine myocarditis, suggests that there is a high likelihood of a causal link between COVID-19 vaccines and death from myocarditis.

Myocarditis after SARS-CoV-2 infection and COVID-19 vaccination: Epidemiology, outcomes, and new perspectives

Study Details
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PUBLICATION DATE: March, 2025
PUBLICATION: RESEAPRO Journals
AUTHORS
M. Nathaniel Mead, Jessica Rose, William Makis, Kirk Milhoan, Nicolas Hulscher, Peter A. McCullough
CORRESPONDENCE TO
mead33@me.com
DOI: 10.61577/ijcri.2025.100001
PMID: Not indexed
ABSTRACT
Myocarditis, typically manifesting as myopericarditis, is among the serious cardiac consequences observed over the course of the COVID-19 pandemic. We performed a comprehensive, evidence-based literature synthesis of findings from clinical trial data reanalyses, post-marketing surveillance, large observational studies, and other diverse research sources that help shed light on the phenomenon of myocarditis post SARS-CoV-2 infection versus COVID-19 vaccine-induced myocarditis. Our conclusions refute several claims previously made by public health agencies and professional associations, namely the following: (1) the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Omicron infections have caused more cases of myocarditis than the COVID-19 mRNA immunizations; (2) mRNA vaccine-induced myocarditis is typically mild, transient, and rare, with no long-term sequelae; and (3) the risk-benefit calculus favors continued use of these products despite evidence of more iatrogenic cases. We address each of these misconceptions by applying a combination of epidemiological, clinical, and immunological perspectives. We urge governments to remove the COVID-19 mRNA products from the market due to the well-documented risk of myocardial damage, a risk that is strongest for younger males (<40 years old).

Risk stratification for future cardiac arrest after COVID-19 vaccination

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: February, 2025
PUBLICATION: PubMed
AUTHORS
Peter A McCullough, Nicolas Hulscher
CORRESPONDENCE TO
nichulscher@gmail.com
DOI: 10.4330/wjc.v17.i2.103909
PMID: 40061285
ABSTRACT
Unheralded cardiac arrest among previously healthy young people without antecedent illness, months or years after coronavirus disease 2019 (COVID-19) vaccination, highlights the urgent need for risk stratification. The most likely underlying pathophysiology is subclinical myopericarditis and reentrant ventricular tachycardia or spontaneous ventricular fibrillation that is commonly precipitated after a surge in catecholamines during exercise or the waking hours of terminal sleep. Small patches of inflammation and/or edema can be missed on cardiac imaging and autopsy, and the heart can appear grossly normal. This paper reviews evidence linking COVID-19 vaccines to cardiac arrest where unfortunately the majority of victims have had no antecedent clinical evaluation. We propose a comprehensive strategy for evaluating cardiovascular risk post-vaccination, incorporating detailed patient history, antibody testing, and cardiac diagnostics in the best attempt to detect abnormalities before sudden cardiac death. This approach aims to identify individuals at higher risk of cardiac events after COVID-19 vaccination and guide appropriate clinical management. It is prudent for each primary care physician to have a pre-established plan when addressing this issue in their practice

Excess Cardiopulmonary Arrest and Mortality after COVID-19 Vaccination in King County, Washington

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: October, 2024
PUBLICATION: Journal of Emergency Medicine
AUTHORS
Nicolas Hulscher, Michael J. Cook, Raphael B. Stricker, Peter A. McCullough
CORRESPONDENCE TO
nichulscher@gmail.com
DOI: 10.33140/JEMOA.02.01.12
PMID: Not Indexed
ABSTRACT
Introduction: Since the onset of widespread COVID-19 vaccination campaigns, there have been concerns about serious cardiovascular adverse events as a result of mass vaccination. This study aimed to estimate excess cardiopulmonary arrest mortality in King County, WA, and investigate any association with COVID-19 vaccination rates. Methods: An exploratory data analysis was performed. Comparative analyses were performed to evaluate the changes in total EMS attendances over time. Excess deaths were calculated using the 2015-2020 cardiopulmonary arrest mortality trend line. The relationship between excess cardiopulmonary arrest mortality and vaccination rates was analyzed using polynomial regression analysis. Results: Approximately 98% of the King County population received at least one dose of a COVID-19 vaccine by 2023. As of August 2nd, 2024, there have been approximately 589,247 confirmed COVID-19 cases in King County. In 20212022, Total EMS attendances in King County sharply increased by 35.34% from 2020 and by 11% from pre-pandemic years. Cases of ‘obvious death’ upon EMS arrival increased by 19.89% in 2020, 36.57% in 2021, and 53.80% in 2022 compared to the 2017-2019 average. We found a 25.7% increase in total cardiopulmonary arrests and a 25.4% increase in cardiopulmonary arrest mortality from 2020 to 2023 in King County, WA. Excess fatal cardiopulmonary arrests were estimated to have increased by 1,236% from 2020 to 2023, rising from 11 excess deaths (95% CI: -12, 34) in 2020 to 147 excess deaths (95% CI: 123, 170) in 2023. A quadratic increase in excess cardiopulmonary arrest mortality was observed with higher COVID-19 vaccination rates. The general population of King County sharply declined by 0.94% (21,300) in 2021, deviating from the expected population size. Applying our model from these data to the entire United States yielded 49,240 excess fatal cardiopulmonary arrests from 2021-2023. Conclusions: We identified a significant ecological and temporal association between excess fatal cardiopulmonary arrests and the COVID-19 vaccination campaign. The increase in excess cardiopulmonary arrest deaths may also be attributed to COVID-19 infection and disruptions in emergency care during the pandemic. Urgent further research is needed to confirm our observations with attention to risk mitigation for incident events and improved survival with resuscitation.

Determinants of COVID-19 vaccine-induced myocarditis

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: January, 2024
PUBLICATION: Sage Journals
AUTHORS
Jessica Rose, Nicolas Hulscher, Peter A McCullough
CORRESPONDENCE TO
nichulscher@gmail.com
DOI: 10.1177/20420986241226566
PMID: 38293564
ABSTRACT
Background:
Following the roll-out of the Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, and Janssen Ad26.COV2.S coronavirus disease 2019 (COVID-19) injections in the United States, millions of individuals have reported adverse events (AEs) using the vaccine adverse events reports system (VAERS). The objective of this analysis is to describe the myocarditis data in VAERS and the COVID-19 vaccines as potential determinants of myocarditis.
Methods:
We used VAERS data to examine the frequency of reporting myocarditis since the beginning of the mass vaccination campaign and compared this with historical values in VAERS and COVID-19 vaccine administration data from the Our World in Data database. We examined myocarditis reports in VAERS in the context of sex, age, and dose. Statistical analysis was done using the Student’s t-test to determine statistically significant differences between ages among myocarditis adverse events (AEs) and the chi-square test to determine relationships between categorical variables with statistical significance.
Results:
We found the number of myocarditis reports in VAERS after COVID-19 vaccination in 2021 was 223 times higher than the average of all vaccines combined for the past 30 years. This represented a 2500% increase in the absolute number of reports in the first year of the campaign when comparing historical values prior to 2021. Demographic data revealed that myocarditis occurred most in youths (50%) and males (69%). A total of 76% of cases resulted in emergency care and hospitalization. Of the total myocarditis reports, 92 individuals died (3%). Myocarditis was more likely after dose 2 (p < 0.00001) and individuals less than 30 years of age were more likely than individuals older than 30 to acquire myocarditis (p < 0.00001).

Sex-specific differences in myocardial injury incidence after COVID-19 mRNA-1273 booster vaccination

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: October, 2023
PUBLICATION: European Journal of Heart Failure
AUTHORS
Natacha Buergin, Pedro Lopez-Ayala, Julia R Hirsiger, Philip Mueller, Daniela Median, Noemi Glarner, Klara Rumora, Timon Herrmann, Luca Koechlin, Philip Haaf, Katharina Rentsch, Manuel Battegay, Florian Banderet, Christoph T Berger, Christian Mueller
CORRESPONDENCE TO
christian.mueller@usb.ch
DOI: 10.1002/ejhf.2978
PMID: 37470105
ABSTRACT
Aims:
To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination.
Methods and results:
Hospital employees scheduled to undergo mRNA-1273 booster vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper limit of normal on day 3 (48-96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against interleukin-1 receptor antagonist (IL-1RA), the SARS-CoV-2-nucleoprotein (NP) and -spike (S1) proteins and an array of 14 inflammatory cytokines were quantified. Among 777 participants (median age 37 years, 69.5% women), 40 participants (5.1%; 95% confidence interval [CI] 3.7-7.0%) had elevated hs-cTnT concentration on day 3 and mRNA-1273 vaccine-associated myocardial injury was adjudicated in 22 participants (2.8% [95% CI 1.7-4.3%]). Twenty cases occurred in women (3.7% [95% CI 2.3-5.7%]), two in men (0.8% [95% CI 0.1-3.0%]). Hs-cTnT elevations were mild and only temporary. No patient had electrocardiographic changes, and none developed major adverse cardiac events within 30 days (0% [95% CI 0-0.4%]). In the overall booster cohort, hs-cTnT concentrations (day 3; median 5, interquartile range [IQR] 4-6 ng/L) were significantly higher compared to matched controls (n = 777, median 3 [IQR 3-5] ng/L, p < 0.001). Cases had comparable systemic reactogenicity, concentrations of anti-IL-1RA, anti-NP, anti-S1, and markers quantifying systemic inflammation, but lower concentrations of interferon (IFN)-λ1 (IL-29) and granulocyte-macrophage colony-stimulating factor (GM-CSF) versus persons without vaccine-associated myocardial injury.
Conclusion:
mRNA-1273 vaccine-associated myocardial injury was more common than previously thought, being mild and transient, and more frequent in women versus men. The possible protective role of IFN-λ1 (IL-29) and GM-CSF warrant further studies.

Autopsy-based histopathological characterization of myocarditis after anti-SARS-CoV-2-vaccination

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: November, 2022
PUBLICATION: Springer Nature
AUTHORS
Constantin Schwab, Lisa Maria Domke, Laura Hartmann, Albrecht Stenzinger, Thomas Longerich, Peter Schirmacher
CORRESPONDENCE TO
peter.schirmacher@med.uni-heidelberg.de
DOI: 10.1007/s00392-022-02129-5
PMID: 36436002
ABSTRACT
Cases of myocarditis, diagnosed clinically by laboratory tests and imaging have been described in the context of mRNA-based anti-SARS-CoV-2 vaccination. Autopsy-based description of detailed histological features of vaccine-induced myocarditis is lacking. We describe the autopsy findings and common characteristics of myocarditis in untreated persons who received anti-SARS-CoV-2 vaccination. Standardized autopsies were performed on 25 persons who had died unexpectedly and within 20 days after anti-SARS-CoV-2 vaccination. In four patients who received a mRNA vaccination, we identified acute (epi-)myocarditis without detection of another significant disease or health constellation that may have caused an unexpected death. Histology showed patchy interstitial myocardial T-lymphocytic infiltration, predominantly of the CD4 positive subset, associated with mild myocyte damage. Overall, autopsy findings indicated death due to acute arrhythmogenic cardiac failure. Thus, myocarditis can be a potentially lethal complication following mRNA-based anti-SARS-CoV-2 vaccination. Our findings may aid in adequately diagnosing unclear cases after vaccination and in establishing a timely diagnosis in vivo, thus, providing the framework for adequate monitoring and early treatment of severe clinical cases.

Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: September, 2022
PUBLICATION: Science Direct
AUTHORS
Joseph Fraiman, Juan Erviti, Mark Jones, Sander Greenland, Patrick Whelan, Robert M. Kaplan, Peter Doshi
CORRESPONDENCE TO
josephfraiman@gmail.com, pdoshi@rx.umaryland.edu
DOI: 10.1016/j.vaccine.2022.08.036
PMID: 36055877
ABSTRACT
Introduction
In 2020, prior to COVID-19 vaccine rollout, the Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We adapted the Brighton Collaboration list to evaluate serious adverse events of special interest observed in mRNA COVID-19 vaccine trials.
Methods
Secondary analysis of serious adverse events reported in the placebo-controlled, phase III randomized clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines in adults (NCT04368728 and NCT04470427), focusing analysis on Brighton Collaboration adverse events of special interest.
Results
Pfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95 % CI −0.4 to 20.6 and −3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated (95 % CI 2.1 to 22.9); risk ratio 1.43 (95 % CI 1.07 to 1.92). The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % CI 1.2 to 34.9); risk ratio 1.36 (95 % CI 1.02 to 1.83). The Moderna trial exhibited a 6 % higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000 (95 % CI –23.2 to 37.4); risk ratio 1.06 (95 % CI 0.84 to 1.33). Combined, there was a 16 % higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2 (95 % CI −3.2 to 29.6); risk ratio 1.16 (95 % CI 0.97 to 1.39).
Discussion
The excess risk of serious adverse events found in our study points to the need for formal harm-benefit analyses, particularly those that are stratified according to risk of serious COVID-19 outcomes. These analyses will require public release of participant level datasets.

A Case Report: Multifocal Necrotizing Encephalitis and Myocarditis after BNT162b2 mRNA Vaccination against COVID-19

Study Details
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PUBLICATION DATE: August, 2022
PUBLICATION: MDPI
AUTHORS
Michael Mörz
CORRESPONDENCE TO
michael.moerz@klinikum-dresden.de
DOI: 10.3390/vaccines10101651
PMID: 36055877
ABSTRACT
Introduction
The current report presents the case of a 76-year-old man with Parkinson’s disease (PD) who died three weeks after receiving his third COVID-19 vaccination. The patient was first vaccinated in May 2021 with the ChAdOx1 nCov-19 vector vaccine, followed by two doses of the BNT162b2 mRNA vaccine in July and December 2021. The family of the deceased requested an autopsy due to ambiguous clinical signs before death. PD was confirmed by post-mortem examinations. Furthermore, signs of aspiration pneumonia and systemic arteriosclerosis were evident. However, histopathological analyses of the brain uncovered previously unsuspected findings, including acute vasculitis (predominantly lymphocytic) as well as multifocal necrotizing encephalitis of unknown etiology with pronounced inflammation including glial and lymphocytic reaction. In the heart, signs of chronic cardiomyopathy as well as mild acute lympho-histiocytic myocarditis and vasculitis were present. Although there was no history of COVID-19 for this patient, immunohistochemistry for SARS-CoV-2 antigens (spike and nucleocapsid proteins) was performed. Surprisingly, only spike protein but no nucleocapsid protein could be detected within the foci of inflammation in both the brain and the heart, particularly in the endothelial cells of small blood vessels. Since no nucleocapsid protein could be detected, the presence of spike protein must be ascribed to vaccination rather than to viral infection. The findings corroborate previous reports of encephalitis and myocarditis caused by gene-based COVID-19 vaccines.

Cardiovascular Manifestation of the BNT162b2 mRNA COVID-19 Vaccine in Adolescents

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: July, 2022
PUBLICATION: MDPI
AUTHORS
Suyanee Mansanguan, Prakaykaew Charunwatthana, Watcharapong Piyaphanee, Wilanee Dechkhajorn, Akkapon Poolcharoen, Chayasin Mansanguan
CORRESPONDENCE TO
chayasin.man@mahidol.ac.th
DOI: 10.3390/tropicalmed7080196
PMID: 36006288
ABSTRACT
This study focuses on cardiovascular manifestation, particularly myocarditis and pericarditis events, after BNT162b2 mRNA COVID-19 vaccine injection in Thai adolescents. This prospective cohort study enrolled students aged 13–18 years from two schools, who received the second dose of the BNT162b2 mRNA COVID-19 vaccine. Data including demographics, symptoms, vital signs, ECG, echocardiography, and cardiac enzymes were collected at baseline, Day 3, Day 7, and Day 14 (optional) using case record forms. We enrolled 314 participants; of these, 13 participants were lost to follow-up, leaving 301 participants for analysis. The most common cardiovascular signs and symptoms were tachycardia (7.64%), shortness of breath (6.64%), palpitation (4.32%), chest pain (4.32%), and hypertension (3.99%). One participant could have more than one sign and/or symptom. Seven participants (2.33%) exhibited at least one elevated cardiac biomarker or positive lab assessments. Cardiovascular manifestations were found in 29.24% of patients, ranging from tachycardia or palpitation to myopericarditis. Myopericarditis was confirmed in one patient after vaccination. Two patients had suspected pericarditis and four patients had suspected subclinical myocarditis. In conclusion, Cardiovascular manifestation in adolescents after BNT162b2 mRNA COVID-19 vaccination included tachycardia, palpitation, and myopericarditis. The clinical presentation of myopericarditis after vaccination was usually mild and temporary, with all cases fully recovering within 14 days. Hence, adolescents receiving mRNA vaccines should be monitored for cardiovascular side effects.

Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: June, 2022
PUBLICATION: Nature
AUTHORS
Stéphane Le Vu, Marion Bertrand, Marie-Joelle Jabagi, Jérémie Botton, Jérôme Drouin, Bérangère Baricault, Alain Weill, Rosemary Dray-Spira, Mahmoud Zureik
CORRESPONDENCE TO
stephane.le-vu@ansm.sante.fr
DOI: 10.1038/s41467-022-31401-5
PMID: 35752614
ABSTRACT
Cases of myocarditis and pericarditis have been reported following the receipt of Covid-19 mRNA vaccines. As vaccination campaigns are still to be extended, we aimed to provide a comprehensive assessment of the association, by vaccine and across sex and age groups. Using nationwide hospital discharge and vaccine data, we analysed all 1612 cases of myocarditis and 1613 cases of pericarditis that occurred in France in the period from May 12, 2021 to October 31, 2021. We perform matched case-control studies and find increased risks of myocarditis and pericarditis during the first week following vaccination, and particularly after the second dose, with adjusted odds ratios of myocarditis of 8.1 (95% confidence interval [CI], 6.7 to 9.9) for the BNT162b2 and 30 (95% CI, 21 to 43) for the mRNA-1273 vaccine. The largest associations are observed for myocarditis following mRNA-1273 vaccination in persons aged 18 to 24 years. Estimates of excess cases attributable to vaccination also reveal a substantial burden of both myocarditis and pericarditis across other age groups and in both males and females.

Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: June, 2022
PUBLICATION: JAMA
AUTHORS
Sarah A Buchan, Chi Yon Seo, Caitlin Johnson, Sarah Alley, Jeffrey C Kwong, Sharifa Nasreen, Andrew Calzavara, Diane Lu, Tara M Harris, Kelly Yu, Sarah E Wilson
CORRESPONDENCE TO
sarah.wilson@oahpp.ca
DOI: 10.1001/jamanetworkopen.2022.18505
PMID: 35749115
ABSTRACT
Importance:
Increased rates of myocarditis or pericarditis following receipt of COVID-19 mRNA vaccines have been observed. However, few available data are associated with differences in rates of myocarditis or pericarditis specific to vaccine products, which may have important implications for vaccination programs.
Objective:
To estimate rates of reported myocarditis or pericarditis following receipt of a COVID-19 mRNA vaccine by product, age, sex, dose number, and interdose interval.
Design, setting, and participants:
This population-based cohort study was conducted in Ontario, Canada (population: 14.7 million) from December 2020 to September 2021 and used data from Ontario’s COVID-19 vaccine registry and passive vaccine-safety surveillance system. All individuals in Ontario, Canada, who received at least 1 dose of COVID-19 mRNA vaccine between December 14, 2020, and September 4, 2021, and had a reported episode of myocarditis or pericarditis following receipt of the COVID-19 vaccine during this period were included. We obtained information on all vaccine doses administered in the province to calculate reported rates of myocarditis or pericarditis.
Exposures:
Receipt of a COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]).
Main outcomes and measures:
All reports of myocarditis or pericarditis meeting levels 1 to 3 of the Brighton Collaboration case definitions were included. Rates and 95% CIs of reported cases of myocarditis or pericarditis per 1 000 000 mRNA vaccine doses administered were calculated by age, sex, dose number, vaccine product, and interdose interval.
Results:
Among 19 740 741 doses of mRNA vaccines administered, there were 297 reports of myocarditis or pericarditis meeting the inclusion criteria; 228 (76.8%) occurred in male individuals, and the median age of individuals with a reported event was 24 years (range, 12-81 years). Of the reported cases, 207 (69.7%) occurred following the second dose of the COVID-19 mRNA vaccine. When restricted to individuals who received their second dose during the period of enhanced passive surveillance (on or after June 1, 2021), the highest rate of myocarditis or pericarditis was observed in male individuals aged 18 to 24 years following mRNA-1273 as the second dose (299.5 cases per 1 000 000 doses; 95% CI, 171.2-486.4 cases per 1 000 000 doses); the rate following BNT162b2 as the second dose was 59.2 cases per 1 000 000 doses (95% CI, 19.2-138.1 cases per 1 000 000 doses). Overall rates for both vaccine products were significantly higher when the interdose interval was 30 or fewer days (BNT162b2: 52.1 cases per 1 000 000 doses [95% CI, 31.8-80.5 cases per 1 000 000 doses]; mRNA-1273: 83.9 cases per 1 000 000 doses [95% CI, 47.0-138.4 cases per 1 000 000 doses]) compared with 56 or more days (BNT162b2: 9.6 cases per 1 000 000 doses [95% CI, 6.5-13.6 cases per 1 000 000 doses]; mRNA-1273: 16.2 cases per 1 000 000 doses [95% CI, 10.2-24.6 cases per 1 000 000 doses]).
Conclusions and relevance:
The findings of this population-based cohort study of Ontario adolescents and adults with myocarditis or pericarditis following mRNA COVID-19 vaccination suggest that vaccine products and interdose intervals, in addition to age and sex, may be associated with the risk of myocarditis or pericarditis after receipt of these vaccines. Vaccination program strategies, such as age-based product considerations and longer interdose intervals, may reduce the risk of myocarditis or pericarditis following receipt of mRNA vaccin

Increased emergency cardiovascular events among under-40 population in Israel during vaccine rollout and third COVID-19 wave

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: April, 2022
PUBLICATION: Nature
AUTHORS
Christopher L. F. Sun, Eli Jaffe, Retsef Levi
CORRESPONDENCE TO
retsef@mit.edu
DOI: 10.1038/s41598-022-10928-z
PMID: 35484304
ABSTRACT
Cardiovascular adverse conditions are caused by coronavirus disease 2019 (COVID-19) infections and reported as side-effects of the COVID-19 vaccines. Enriching current vaccine safety surveillance systems with additional data sources may improve the understanding of COVID-19 vaccine safety. Using a unique dataset from Israel National Emergency Medical Services (EMS) from 2019 to 2021, the study aims to evaluate the association between the volume of cardiac arrest and acute coronary syndrome EMS calls in the 16–39-year-old population with potential factors including COVID-19 infection and vaccination rates. An increase of 25% was detected in both call types during January–May 2021, compared with the years 2019–2020. Using Negative Binomial regression models, the weekly emergency call counts were significantly associated with the rates of 1st and 2nd vaccine doses administered to this age group but were not with COVID-19 infection rates. While not establishing causal relationships, the findings raise concerns regarding vaccine-induced undetected severe cardiovascular side-effects and underscore the already established causal relationship between vaccines and myocarditis, a frequent cause of unexpected cardiac arrest in young individuals. Surveillance of potential vaccine side-effects and COVID-19 outcomes should incorporate EMS and other health data to identify public health trends (e.g., increased in EMS calls), and promptly investigate potential underlying causes.

SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents

Study Details
FULL TEXT LINK: View Paper
PUBLICATION DATE: April, 2022
PUBLICATION: JAMA Cardiology
AUTHORS
Øystein Karlstad, MSc Pharm, PhD; Petteri Hovi, MD, PhD; Anders Husby, MD, PhD;
Tommi Härkänen, PhD; Randi Marie Selmer, MSc, PhD; Nicklas Pihlström, MSc; Jørgen Vinsløv Hansen, MSc, PhD; Hanna Nohynek, MD, PhD; Nina Gunnes, MSc, PhD; Anders Sundström, BA, PhD; Jan Wohlfahrt, MSc, DMSC; Tuomo A. Nieminen, MSocSc; Maria Grünewald, MSc, PhD; Hanne Løvdal Gulseth, MD, PhD; Anders Hviid, MSc, DMSC; Rickard Ljung, MD, PhD, MPH
CORRESPONDENCE TO
rickard.ljung@lakemedelsverket.se
DOI: 10.1001/jamacardio.2022.0583
PMID: 35442390
ABSTRACT
Importance
Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged.
Objective
To evaluate the risks of myocarditis and pericarditis following SARS-CoV-2 vaccination by vaccine product, vaccination dose number, sex, and age.
Design, Setting, and Participants
Four cohort studies were conducted according to a common protocol, and the results were combined using meta-analysis. Participants were 23 122 522 residents aged 12 years or older. They were followed up from December 27, 2020, until incident myocarditis or pericarditis, censoring, or study end (October 5, 2021). Data on SARS-CoV-2 vaccinations, hospital diagnoses of myocarditis or pericarditis, and covariates for the participants were obtained from linked nationwide health registers in Denmark, Finland, Norway, and Sweden.
Exposures
The 28-day risk periods after administration date of the first and second doses of a SARS-CoV-2 vaccine, including BNT162b2, mRNA-1273, and AZD1222 or combinations thereof. A homologous schedule was defined as receiving the same vaccine type for doses 1 and 2.
Main Outcomes and Measures
Incident outcome events were defined as the date of first inpatient hospital admission based on primary or secondary discharge diagnosis for myocarditis or pericarditis from December 27, 2020, onward. Secondary outcome was myocarditis or pericarditis combined from either inpatient or outpatient hospital care. Poisson regression yielded adjusted incidence rate ratios (IRRs) and excess rates with 95% CIs, comparing rates of myocarditis or pericarditis in the 28-day period following vaccination with rates among unvaccinated individuals.
Results
Among 23 122 522 Nordic residents (81% vaccinated by study end; 50.2% female), 1077 incident myocarditis events and 1149 incident pericarditis events were identified. Within the 28-day period, for males and females 12 years or older combined who received a homologous schedule, the second dose was associated with higher risk of myocarditis, with adjusted IRRs of 1.75 (95% CI, 1.43-2.14) for BNT162b2 and 6.57 (95% CI, 4.64-9.28) for mRNA-1273. Among males 16 to 24 years of age, adjusted IRRs were 5.31 (95% CI, 3.68-7.68) for a second dose of BNT162b2 and 13.83 (95% CI, 8.08-23.68) for a second dose of mRNA-1273, and numbers of excess events were 5.55 (95% CI, 3.70-7.39) events per 100 000 vaccinees after the second dose of BNT162b2 and 18.39 (9.05-27.72) events per 100 000 vaccinees after the second dose of mRNA-1273. Estimates for pericarditis were similar.
Conclusions and Relevance
Results of this large cohort study indicated that both first and second doses of mRNA vaccines were associated with increased risk of myocarditis and pericarditis. For individuals receiving 2 doses of the same vaccine, risk of myocarditis was highest among young males (aged 16-24 years) after the second dose. These findings are compatible with between 4 and 7 excess events in 28 days per 100 000 vaccinees after BNT162b2, and between 9 and 28 excess events per 100 000 vaccinees after mRNA-1273. This risk should be balanced against the benefits of protecting against severe COVID-19 disease.

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