Association between COVID-19 vaccines and paediatric safety outcomes in children and adolescents aged 5-19 years in the Nordic countries: Myocarditis, pericarditis and thromboembolic events

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Nationwide register-based study

Study drug and medical condition

• Medical condition to be studied:
  COVID-19

  COVID-19 immunisation

Population studied

• Short description of the study population:
  Subjects aged 5-19 years identified from the four larger Nordic countries (Denmark, Finland, Norway, and Sweden) for the study period of 1 January 2021 to 31 October 2022.
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)
• Special population of interest:
  Other
• Special population of interest, other:
  COVID-19 patients
• Estimated number of subjects:
  4200000

Study design details

• Main study objective:
  The overall aim of this project is to conduct nationwide cohort studies of current COVID-19 vaccine safety issues in children/adolescents. The aim of this project also is to conduct a feasibility study of the possible association between COVID-19 vaccination in children and adolescents and a wide range of immune-mediated conditions.
• Outcomes:
  To evaluate the association between COVID-19 vaccines and myocarditis/pericarditis, and thromboembolic and thrombocytopenic outcomes in children/adolescents aged 5 to 19 years. To conduct a feasibility study on the association between COVID-19 vaccination and 47 different immune-mediated diseases including autoimmune hepatitis and type 1 diabetes in children/adolescents aged 5 to 19 years. To evaluate the association between COVID-19 infection and myocarditis/pericarditis and thromboembolic and thrombocytopenic outcomes in children/adolescents aged 5 to 19 years. To evaluate the association between COVID-19 infection and 47 different immune-mediated diseases in children/adolescents aged 5 to 19 years.
• Data analysis plan:
  Nationwide register-based cohort studies in Denmark, Finland, Norway and Sweden. We will analyse the follow-up periods and outcome counts using three complementary survival analysis approaches, 1) observed vs expected analyses providing standardized morbidity ratios and risk differences, 2) contemporary cohort analyses providing adjusted rate ratios and excess risk, and 3) self-controlled case series analyses nested in the cohorts providing rate ratios and excess risk, which are by design unconfounded by time-independent covariates. We will include an adjustment age, sex, year and calendar month, country-specific region, maternal country of birth (Nordic, Western, non-Western), comorbidities and vaccination priority group.