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Comparative effectiveness of heterologous third dose vaccine schedules against severe covid-19 during omicron predominance in Nordic countries: population based cohort analyses.
BMJ. 2023 07 24; 382:e074325.BMJ

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.

Authors+Show Affiliations

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark nian@ssi.dk.Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.Infectious Disease Control and Vaccinations Unit, Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland.Division of Licensing, Swedish Medical Products Agency, Uppsala, Sweden.Department of Infection Control and Preparedness, Norwegian Institute of Public Health, Oslo, Norway.Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.Infectious Disease Control and Vaccinations Unit, Department of Health Security, Finnish Institute for Health and Welfare, Helsinki, Finland. Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland.Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.Department of Infectious Disease Epidemiology and Prevention, Statens Serum Institut, Copenhagen, Denmark.Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.Data Analytics Center, Danish Medicines Agency, Copenhagen, Denmark.European Medicines Agency, Amsterdam, Netherlands.European Medicines Agency, Amsterdam, Netherlands.Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark. Clinical Pharmacology, Odense University Hospital, Odense, Denmark.Department of Infection Control and Vaccines, Norwegian Institute of Public Health, Oslo, Norway.Division of Use and Information, Swedish Medical Products Agency, Uppsala, Sweden. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

37487623

Citation

Andersson, Niklas Worm, et al. "Comparative Effectiveness of Heterologous Third Dose Vaccine Schedules Against Severe Covid-19 During Omicron Predominance in Nordic Countries: Population Based Cohort Analyses." BMJ (Clinical Research Ed.), vol. 382, 2023, pp. e074325.
Andersson NW, Thiesson EM, Baum U, et al. Comparative effectiveness of heterologous third dose vaccine schedules against severe covid-19 during omicron predominance in Nordic countries: population based cohort analyses. BMJ. 2023;382:e074325.
Andersson, N. W., Thiesson, E. M., Baum, U., Pihlström, N., Starrfelt, J., Faksová, K., Poukka, E., Lund, L. C., Hansen, C. H., Aakjær, M., Kjær, J., Cohet, C., Goossens, M., Andersen, M., Hallas, J., Meijerink, H., Ljung, R., & Hviid, A. (2023). Comparative effectiveness of heterologous third dose vaccine schedules against severe covid-19 during omicron predominance in Nordic countries: population based cohort analyses. BMJ (Clinical Research Ed.), 382, e074325. https://doi.org/10.1136/bmj-2022-074325
Andersson NW, et al. Comparative Effectiveness of Heterologous Third Dose Vaccine Schedules Against Severe Covid-19 During Omicron Predominance in Nordic Countries: Population Based Cohort Analyses. BMJ. 2023 07 24;382:e074325. PubMed PMID: 37487623.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effectiveness of heterologous third dose vaccine schedules against severe covid-19 during omicron predominance in Nordic countries: population based cohort analyses. AU - Andersson,Niklas Worm, AU - Thiesson,Emilia Myrup, AU - Baum,Ulrike, AU - Pihlström,Nicklas, AU - Starrfelt,Jostein, AU - Faksová,Kristýna, AU - Poukka,Eero, AU - Lund,Lars Christian, AU - Hansen,Christian Holm, AU - Aakjær,Mia, AU - Kjær,Jesper, AU - Cohet,Catherine, AU - Goossens,Mathijs, AU - Andersen,Morten, AU - Hallas,Jesper, AU - Meijerink,Hinta, AU - Ljung,Rickard, AU - Hviid,Anders, Y1 - 2023/07/24/ PY - 2023/7/26/medline PY - 2023/7/25/pubmed PY - 2023/7/24/entrez SP - e074325 EP - e074325 JF - BMJ (Clinical research ed.) JO - BMJ VL - 382 N2 - 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. SN - 1756-1833 UR - https://www.unboundmedicine.com/medline/citation/37487623/Comparative_effectiveness_of_heterologous_third_dose_vaccine_schedules_against_severe_covid_19_during_omicron_predominance_in_Nordic_countries:_population_based_cohort_analyses_ DB - PRIME DP - Unbound Medicine ER -