Clinical outcomes of myocarditis after SARS-CoV-2 mRNA vaccination in four Nordic countries: population based cohort study

Objective To investigate the clinical outcomes of myocarditis associated with mRNA vaccines against the SARS-CoV-2 virus compared with other types of myocarditis. Design Population based cohort study. Setting Nationwide register data from four Nordic countries (Denmark, Finland, Norway, and Sweden), from 1 January 2018 to the latest date of follow-up in 2022. Participants The Nordic myocarditis cohort; 7292 individuals aged ≥12 years who had an incident diagnosis of myocarditis as a main or secondary diagnosis, in a population of 23 million individuals in Denmark, Finland, Norway, and Sweden. Main outcome measures Heart failure, or death from any cause within 90 days of admission to hospital for new onset myocarditis, and hospital readmission within 90 days of discharge to hospital for new onset myocarditis. Clinical outcomes of myocarditis associated with SARS-CoV-2 mRNA vaccination, covid-19 disease, and conventional myocarditis were compared. Results In 2018-22, 7292 patients were admitted to hospital with new onset myocarditis, with 530 (7.3%) categorised as having myocarditis associated with SARS-CoV-2 mRNA vaccination, 109 (1.5%) with myocarditis associated with covid-19 disease, and 6653 (91.2%) with conventional myocarditis. At the 90 day follow-up, 62, nine, and 988 patients had been readmitted to hospital in each group (vaccination, covid-19, and conventional myocarditis groups, respectively), corresponding to a relative risk of readmission of 0.79 (95% confidence interval 0.62 to 1.00) and 0.55 (0.30 to 1.04) for the vaccination type and covid-19 type myocarditis groups, respectively, compared with the conventional myocarditis group. At the 90 day follow-up, 27, 18, and 616 patients had a diagnosis of heart failure or died in the vaccination type, covid-19 type, and conventional myocarditis groups, respectively. The relative risk of heart failure within 90 days was 0.56 (95% confidence interval 0.37 to 0.85) and 1.48 (0.86 to 2.54) for myocarditis associated with vaccination and covid-19 disease, respectively, compared with conventional myocarditis; the relative risk of death was 0.48 (0.21 to 1.09) and 2.35 (1.06 to 5.19), respectively. Among patients aged 12-39 years with no predisposing comorbidities, the relative risk of heart failure or death was markedly higher for myocarditis associated with covid-19 disease than for myocarditis associated with vaccination (relative risk 5.78, 1.84 to 18.20). Conclusions Compared with myocarditis associated with covid-19 disease and conventional myocarditis, myocarditis after vaccination with SARS-CoV-2 mRNA vaccines was associated with better clinical outcomes within 90 days of admission to hospital.

[1]  Jens K. Boldsen,et al.  Seroprevalence and infection fatality rate of the SARS-CoV-2 Omicron variant in Denmark: A nationwide serosurveillance study , 2022, The Lancet Regional Health - Europe.

[2]  M. Bertrand,et al.  Age and sex-specific risks of myocarditis and pericarditis following Covid-19 messenger RNA vaccines , 2022, Nature Communications.

[3]  S. Malhotra,et al.  Myocarditis after COVID‐19 mRNA vaccination: A systematic review of case reports and case series , 2022, Clinical cardiology.

[4]  Sarah E. Wilson,et al.  Epidemiology of Myocarditis and Pericarditis Following mRNA Vaccination by Vaccine Product, Schedule, and Interdose Interval Among Adolescents and Adults in Ontario, Canada , 2022, JAMA network open.

[5]  M. Oster,et al.  Comparison of Multisystem Inflammatory Syndrome in Children–Related Myocarditis, Classic Viral Myocarditis, and COVID‐19 Vaccine‐Related Myocarditis in Children , 2022, Journal of the American Heart Association.

[6]  T. Härkänen,et al.  SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents , 2022, JAMA cardiology.

[7]  E. Sagiv,et al.  Persistent Cardiac Magnetic Resonance Imaging Findings in a Cohort of Adolescents with Post-Coronavirus Disease 2019 mRNA Vaccine Myopericarditis , 2022, The Journal of Pediatrics.

[8]  V. Saliba,et al.  Effectiveness of BNT162b2 against COVID-19 in adolescents , 2022, The Lancet Infectious Diseases.

[9]  Michael John Smith,et al.  Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021. , 2022, JAMA.

[10]  N. Andrews,et al.  Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines , 2022, The New England journal of medicine.

[11]  H. Sørensen,et al.  SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study , 2021, BMJ.

[12]  K. Khunti,et al.  Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection , 2021, Nature Medicine.

[13]  A. Wallace,et al.  SARS-CoV-2 vaccine protection and deaths among US veterans during 2021 , 2021, Science.

[14]  R. Balicer,et al.  Myocarditis after Covid-19 Vaccination in a Large Health Care Organization , 2021, The New England journal of medicine.

[15]  Manfred S. Green,et al.  Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel , 2021, The New England journal of medicine.

[16]  C. Torp‐Pedersen,et al.  Mortality and ventricular arrhythmia after acute myocarditis: a nationwide registry-based follow-up study , 2021, Open Heart.

[17]  O. Schueler‐Furman,et al.  Harnessing protein folding neural networks for peptide–protein docking , 2021, Nature Communications.

[18]  L. Cooper,et al.  Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military. , 2021, JAMA cardiology.

[19]  Antonio Gasparrini,et al.  An extended mixed‐effects framework for meta‐analysis , 2019, Statistics in medicine.

[20]  H. Bøtker,et al.  Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study , 2016, BMJ Open.

[21]  Gun Peggy Knudsen,et al.  Ethical aspects of registry-based research in the Nordic countries , 2015, Clinical epidemiology.

[22]  C. Pipper,et al.  [''R"--project for statistical computing]. , 2008, Ugeskrift for laeger.