Adults who received different primary and booster COVID-19 vaccines had better protection against severe, omicron-related COVID-19 outcomes compared with those receiving the same vaccines for the primary and booster doses. Heterologous booster schedules (3 doses) were also more protective than primary schedules (2 doses).
Population-based cohort analyses were conducted for COVID-19 vaccinations received by all adults receiving COVID-19 vaccines in Denmark, Finland, Norway, and Sweden from late 2020 through late 2021, a period of omicron predominance. Participants had received at least a primary vaccination schedule of AZD1222 (Oxford-AstraZeneca) or monovalent SARS-CoV-2 wild type (ancestral) strain-based mRNA vaccines BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna), in any combination.
The main outcome measures were the combined risks of COVID-19–related hospital admission and death with COVID-19 and additional outcomes of COVID-19–related admission to an intensive care unit and SARS-CoV-2 infection. “Across the four Nordic countries, 1,086,418 participants had received a heterologous booster schedule of AZD1222+BNT162b2 or mRNA-1273 and 2,505,093 had received a heterologous booster schedule of BNT162b2+mRNA-1273,” the authors write. “Compared with the primary schedule only (two doses), the vaccine effectiveness of heterologous booster schedules comprising AZD1222+BNT162b2 or mRNA-1273 and BNT162b2+mRNA-1273 was 82.7% (95% confidence interval 77.1% to 88.2%) and 81.5% (78.9% to 84.2%) for covid-19 related hospital admission and 95.9% (91.6% to 100.0%) and 87.5% (82.5% to 92.6%) for death with covid-19, respectively. Homologous mRNA booster schedules were similarly associated with increased protection against covid-19 related hospital admission (≥76.5%) and death with covid-19 (≥84.1%) compared with previous primary course vaccination only. When a heterologous booster schedule was compared with the homologous booster schedule, vaccine effectiveness was 27.2% (3.7% to 50.6%) for AZD1222+BNT162b2 or mRNA-1273 and 23.3% (15.8% to 30.8%) for BNT162b2+mRNA-1273 schedules against covid-19 related hospital admission and 21.7% (−8.3% to 51.7%) and 18.4% (−15.7% to 52.5%) against death with covid-19, respectively.”