Comparative effectiveness of heterologous third dose vaccine schedules against severe covid-19 during omicron predominance in Nordic countries: population based cohort analyses

Abstract

Objective To investigate the comparative vaccine effectiveness of heterologous booster schedules (ie, three vaccine doses) compared with primary schedules (two vaccine doses) and with homologous mRNA vaccine booster schedules (three vaccine doses) during a period of omicron predominance. Design Population based cohort analyses. Setting Denmark, Finland, Norway, and Sweden, 27 December 2020 to 31 December 2022. Participants All adults aged ≥18 years who 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. Main outcome measures The main outcome measure was country 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. During a period of omicron predominance, these outcomes were compared in those who received a heterologous booster versus primary schedule (matched analyses) and versus those who received a homologous mRNA vaccine booster (weighted analyses). Follow-up was for 75 days from day 14 after the booster dose; comparative vaccine effectiveness was calculated as 1–risk ratio. Results 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. 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. Conclusion Heterologous booster schedules are associated with increased protection against severe, omicron related covid-19 outcomes compared with primary course schedules and homologous booster schedules.

COVID-19 Vaccination Effectiveness in the General Population of an Italian Province: Two Years of Follow-Up

“…While several studies reported a higher effectiveness of mRNA-1273 compared to BNT162b2 against infection and severe COVID-19 outcomes both as a primary and booster vaccination [ 51 , 52 , 53 , 54 , 55 , 56 ], in the present cohort we observed a significantly higher protection of mRNA-1273 only against SARS-CoV-2 infections or after a single dose, and the subjects who received three or more doses of mRNA-1273 showed a higher likelihood of death, as compared to the recipients of BNT162b2 only. In contrast, we observed a greater protection conferred by heterologous booster (mixed) vaccination compared with a homologous booster with BNT162b2 only, in line with the findings of immunogenicity [ 57 ] and other population-based [ 20 , 58 , 59 ] studies. Notably, however, the results are difficult to compare due to the diverse booster schedules adopted across countries.…”

Vaccine Effectiveness against GP-Attended Symptomatic COVID-19 and Hybrid Immunity among Adults in Hungary during the 2022–2023 Respiratory Season Dominated by Different SARS-CoV-2 Omicron Subvariants

“…In this study, 87.8% of heterologous vaccination series included an mRNA booster dose. According to a previous comparative analysis, heterologous booster schedules conferred slightly better protection against COVID-19-related outcomes than homologous mRNA vaccine booster schedules [29].…”

Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study

“…The reasons for the high attack rate during the study period are complicated, but the main reason should be it has been a long time (about 8–12 months) since the last dose of vaccination. The durability of the protection of COVID-19 vaccines is not good and the protection waned quickly after the vaccination, regardless of the types of COVID-19 vaccines, which has been wildly observed [ 19 ]. In addition, another probable reason is that the population in China had taken a zero-COVID policy and experienced a long period of lock-down with no natural exposure to any SARS-CoV-2 virus, which hurdled to achieve herd immunity against COVID-19, while the SARS-CoV-2 were spreading around in other areas.…”