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

Vu, Stéphane Le; Bertrand, Marion; Jabagi, Marie-Joëlle; Botton, Jérémie; Drouin, Jérôme; Baricault, Bérangère; Weill, Alain; Dray‐Spira, Rosemary; Zureik, Mahmoud

doi:10.1038/s41467-022-31401-5

Cited by 86 publications

(68 citation statements)

References 31 publications

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“…Extending our previous study, 6 we conducted a matched case-control study within the entire French population aged 12 or older, from December, 27, 2020 to January, 31, 2022. We included all 4,890 cases of myocarditis admitted to French hospitals along with 48,900 controls of the general population matched for gender, age, and area of residency.…”

Section: Main Textmentioning

confidence: 99%

“…Extending our previous study 1 , we conducted a matched case-control study within the entire French population aged 12 or older, from the beginning of the Covid-19 vaccination campaign in December, 27, 2020 to January, 31, 2022.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…In addition to the matching variables (age, gender, and area of residence) and the initial covariates 1 potentially associated with a risk of myocarditis or vaccine exposure (history of myocarditis in last 5 years, SARS-CoV-2 infection within a month, and socio-economic level), we included a set of covariates in the analyses. These binary variables reflected a prior history (within 5 years unless otherwise mentioned) of the following conditions: sarcoidosis, opioid use disorder, coronary artery disease and myocardial infarction, heart failure, antihypertensive drug use, arrhythmia, diabetes, autoimmune disease, respiratory disease, active cancer, and antibiotic use (within a month).…”

Section: Supplementary Informationmentioning

confidence: 99%

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Risk of Myocarditis after Covid-19 mRNA Vaccination: Impact of Booster Dose and Dosing Interval

Vu¹,

Bertrand²,

Jabagi³

et al. 2022

Preprint

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Covid-19 mRNA vaccines have been shown to be associated with a short-term increased risk of myocarditis, with the highest risk observed after the second dose compared to the first. The extent of the risk associated with more distant booster doses is less clear. Here, we aimed to assess the relation between dosing interval and the risk of myocarditis, for both the two-dose primary series and the third dose (first booster). Extending our previous matched case-control study, we included 4 890 cases of myocarditis aged 12 or more and 48 900 controls up to January 31, 2022. We found that the risk of myocarditis remained elevated after the booster dose and that longer intervals between each consecutive dose (including booster doses) may decrease the occurrence of vaccine-associated myocarditis.

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Section: Main Textmentioning

confidence: 99%

Section: Supplementary Informationmentioning

confidence: 99%

Section: Supplementary Informationmentioning

confidence: 99%

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Risk of Myocarditis after Covid-19 mRNA Vaccination: Impact of Booster Dose and Dosing Interval

Vu¹,

Bertrand²,

Jabagi³

et al. 2022

Preprint

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“…Indeed, two studies reported that COVID-19 mRNA vaccine-induced myocarditis disproportionately affected adolescents (reporting odds ratio (ROR): 22.3; 95% confidence interval (CI): 19.2-25.9), 18-29-year-olds (ROR: 6.6; 95% CI: 5.9-7.5), and males (ROR: 9.4; 95% CI: 8.3-10.6) [ 5 , 6 ]. These findings were supported by another large registry study that identified increased myocarditis risk following SARS-CoV-2 mRNA vaccination, with the highest risk detected in people aged 18-24 years, particularly after the second dose, where 8.1-fold increased risk after the BNT162b2 SARS-CoV-2 mRNA vaccine (95% CI: 6.7-9.9) and 30-fold increased risk after the mRNA-1273 SARS-CoV-2 vaccine (95% CI: 21-43) were reported [ 7 ]. An Israeli government dataset demonstrated 13.6-fold increased myocarditis risk (95% CI: 9.3-19.2) among males aged between 16 and 19 years compared to the expected following historical data, while a ninefold increased myocarditis risk (95% CI: 4.5-17.8) was recorded when compared to unvaccinated people of similar age and sex during the same period [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Not only were myocarditis risks identified, but a great burden following these cardiac events was also described [ 7 ]. Indeed, young males with comorbidities may experience dramatic cardiac remodeling following SARS-CoV-2 mRNA vaccination [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Catecholamines Are the Key Trigger of COVID-19 mRNA Vaccine-Induced Myocarditis: A Compelling Hypothesis Supported by Epidemiological, Anatomopathological, Molecular, and Physiological Findings

Cadegiani¹

2022

Cureus

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine-induced myocarditis is a rare but well-documented complication in young males. The increased incidence of sudden death among athletes following vaccination has been reported and requires further investigation. Whether the risk of myocarditis, a known major cause of sudden death in young male athletes, also increases after coronavirus disease 2019 (COVID-19) infection is unknown. The severity and implications of these critical adverse effects require a thorough analysis to elucidate their key triggering mechanisms. The present review aimed to evaluate whether there is a justification to hypothesize that catecholamines in a “hypercatecholaminergic” state are the key trigger of SARS-CoV-2 mRNA vaccine-induced myocarditis and related outcomes and whether similar risks are also present following COVID-19 infection. A thorough, structured scoping review of the literature was performed to build the hypothesis through three pillars: detection of myocarditis risk, potential alterations and abnormalities identified after SARS-CoV-2 mRNA vaccination or COVID-19 infection and consequent events, and physiological characteristics of the most affected population. The following terms were searched in indexed and non-indexed peer review articles and recent preprints (<12 months): agent, “SARS-CoV-2” or “COVID-19”; event, “myocarditis” or “sudden death(s)” or “myocarditis+sudden death(s)” or “cardiac event(s)”; underlying cause, “mRNA” or “spike protein” or “infection” or “vaccine”; proposed trigger, “catecholamine(s)” or “adrenaline” or “epinephrine” or “noradrenaline” or “norepinephrine” or “testosterone”; and affected population, “young male(s)” or “athlete(s).” The rationale and data that supported the hypothesis were as follows: SARS-CoV-2 mRNA vaccine-induced myocarditis primarily affected young males, while the risk was not observed following COVID-19 infection; independent autopsies or biopsies of patients who presented post-SARS-CoV-2 mRNA vaccine myocarditis in different geographical regions enabled the conclusion that a primary hypercatecholaminergic state was the key trigger of these events; SARS-CoV-2 mRNA was densely present, and SARS-CoV-2 spike protein was progressively produced in adrenal medulla chromaffin cells, which are responsible for catecholamine production; the dihydroxyphenylalanine decarboxylase enzyme that converts dopamine into noradrenaline was overexpressed in the presence of SARS-CoV-2 mRNA, leading to enhanced noradrenaline activity; catecholamine responses were physiologically higher in young adults and males than in other populations; catecholamine responses and resting catecholamine production were higher in male athletes than in non-athletes; catecholamine responses to stress and its sensitivity were enhanced in the presence of androgens; and catecholamine expressions in young male athletes were already high at baseline, were higher following vaccination, and were higher than those in non-vaccinated athle...

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Long-Term Prognosis of Patients With Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2 Infection, or Conventional Etiologies

Semenzato,

Le Vu,

Botton

et al. 2024

JAMA

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ImportanceAlthough patients with myocarditis after COVID-19 mRNA vaccination appear to have a good prognosis near hospital discharge, their longer-term prognosis and management remain unknown.ObjectiveTo study the cardiovascular complications of post–COVID-19 mRNA vaccination myocarditis and other types of myocarditis during an 18-month follow-up, as well as disease management based on a study of the frequency of medical procedures and drug prescriptions.Design, Setting, and ParticipantsIn this cohort study based on the French National Health Data System, all individuals aged 12 to 49 years hospitalized for myocarditis in France between December 27, 2020, and June 30, 2022, were identified.ExposureIndividuals were categorized as having postvaccine myocarditis (within 7 days after COVID-19 mRNA vaccine), post–COVID-19 myocarditis (within 30 days of SARS-CoV-2 infection), or conventional myocarditis.Main Outcomes and MeasuresThe occurrence of clinical outcomes (hospital readmission for myopericarditis, other cardiovascular events, all-cause death, and a composite outcome of these events) over the 18 months following hospital admission were analyzed using weighted Cox models to standardize the comparisons with the conventional myocarditis group. Also, medical management after hospital discharge was longitudinally assessed using generalized estimated equation models.ResultsIn total, 4635 individuals were hospitalized for myocarditis: 558 with postvaccine myocarditis, 298 with post–COVID-19 myocarditis, and 3779 with conventional myocarditis. Patients with postvaccine myocarditis were younger than those with post–COVID-19 and conventional myocarditis (mean [SD] age of 25.9 [8.6], 31.0 [10.9], and 28.3 [9.4] years, respectively) and were more frequently men (84%, 67%, and 79%). Patients with postvaccine myocarditis had a lower standardized incidence of the composite clinical outcome than those with conventional myocarditis (32/558 vs 497/3779 events; weighted hazard ratio, 0.55 [95% CI, 0.36-0.86]), whereas individuals with post–COVID-19 myocarditis had similar results (36/298 events; weighted hazard ratio, 1.04 [95% CI, 0.70-1.52]). The standardized frequency of medical procedures and drugs prescribed in patients with postvaccine myocarditis or post–COVID-19 myocarditis followed a similar trend in the 18 months following hospital discharge to that of patients with conventional myocarditis.Conclusions and RelevancePatients with post–COVID-19 mRNA vaccination myocarditis, contrary to those with post–COVID-19 myocarditis, show a lower frequency of cardiovascular complications than those with conventional myocarditis at 18 months. However, affected patients, mainly healthy young men, may require medical management up to several months after hospital discharge.

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

Cited by 86 publications

References 31 publications

Risk of Myocarditis after Covid-19 mRNA Vaccination: Impact of Booster Dose and Dosing Interval

Risk of Myocarditis after Covid-19 mRNA Vaccination: Impact of Booster Dose and Dosing Interval

Catecholamines Are the Key Trigger of COVID-19 mRNA Vaccine-Induced Myocarditis: A Compelling Hypothesis Supported by Epidemiological, Anatomopathological, Molecular, and Physiological Findings

Long-Term Prognosis of Patients With Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2 Infection, or Conventional Etiologies

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