Comparative effectiveness of heterologous and homologous primary- and booster SARS-CoV-2 vaccination schedules in the Nordic countries

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)
• 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:
  The study cohort consist of all individuals aged 5 years or older at date of first vaccination identified from the nationwide registers including Denmark, Finland, Norway and Sweden during the study period of 27 December 2020 to 28 February 2022.; Inclusion criteria: ; • having received at least the primary immunisation (i.e. 1. and 2. vaccine dose against covid-19) with either AZD1222, BNT162b2 or the mRNA-1273 vaccines (for the purpose of objective #5, being vaccinated was not an eligibility criterion), ; • known residency within the specific country, ; • and no positive reverse transcription polymerase chain reaction (PCR) test before the study period start and before receiving a 2. or 3. dose in the distinct schedule evaluated.
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Other
• Special population of interest, other:
  COVID-19 patients
• Estimated number of subjects:
  19600000

Study design details

• Main study objective:
  The overall aim of this project is to provide combined and country-specific (Denmark, Finland, Norway and Sweden) estimates of covid-19 vaccination schedule effectiveness using comparative study designs.
• Outcomes:
  To provide comparative vaccination effectiveness (VE) estimates for: - Heterologous primary (2-dose) schedules compared to homologous primary (2-dose) schedules as well as heterologous booster (3-dose) schedules compared to homologous booster (3-dose) schedules. - And both heterologous and homologous booster (3-dose) schedules compared to heterologous and homologous primary (2-dose) schedules. - To provide comparative VE estimates for selected schedules in the periods of Alpha, Delta and Omicron dominance (with variant specific endpoint information to the extent this is possible). - To explore a) waning of immunity comparing time-since vaccination periods within selected schedules and b) comparative waning comparing time-since vaccination across selected schedules.
• Data analysis plan:
  Nationwide register-based cohort studies in Denmark, Finland, Norway and Sweden during the study period 27 December 2020 to 28 February 2022. We will compare schedules head-to-head and provide comparative VE estimates using survival analysis to estimate risk differences and risk ratios from adjusted survival curves. We will include adjustment for age, calendar period, sex, comorbidities and vaccination priority group.