Abstract
Objective:
Estimate the effectiveness and comparative effectiveness of booster vaccination with bivalent original/omicron BA.1 mRNA-1273 (Moderna) and original/omicron BA.1 BNT162b2 (Pfizer-BioNTech) against COVID-19 hospitalisation and death in adults aged ≥50 years.
Design:
Matched cohort studies emulating target trials.
Setting:
With approval of NHS England, we analysed linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform.
Participants:
For comparison of boosting with no boosting, 3,464,877 adults eligible for booster vaccination during the autumn 2022 UK COVID-19 vaccine rollout, registered with a general practice using the TPP SystmOne clinical information system in England. For the between-vaccine comparison 531,129 boosted pairs.
Interventions:
Vaccination with bivalent BA.1 mRNA-1273 or BNT162b2.
Main outcome measures:
COVID-19-related hospital admission or death, non-COVID-19 death, fracture (negative control outcome).
Results:
In approximately 2.5-million person-years follow up there were 14,436 COVID-19-related hospital admissions, 1,152 COVID-19-related deaths, 32,184 non-COVID-19 deaths, and 52,758 fractures. The 350-day risks/1000 of COVID-19 hospitalisation and COVID-19 death were 3.78 (95% CI 3.65-3.91) and 0.29 (0.26, 0.33) respectively after boosting and 6.81 (6.65-6.98) and 0.61 (0.56, 0.66) without boosting. Over 350 days’ follow-up, adjusted hazard ratios were: COVID-19 hospitalisation 0.51 (95% CI 0.50, 0.53); COVID-19 death 0.45 (0.40, 0.51); non-COVID-19 death 0.56 (0.55, 0.58) and fracture 0.89 (0.87, 0.91). Booster effectiveness waned over time, with greatest effectiveness in the first 70 days after vaccination. The 350-day risks of COVID-19 hospitalisation, COVID-19 death and fracture were similar for the two vaccine brands but higher in the bivalent mRNA-1273 group for non-COVID-19 death (risk difference per 1000 0.88 [0.35, 1.40]).
Conclusions:
Rates of COVID-19-related hospitalisation and death were substantially lower after bivalent original/omicron BA.1 mRNA booster vaccine than in people who remained unboosted. Apparent protection against fracture suggests some unmeasured confounding. Outcomes appeared similar for the Moderna and Pfizer-BioNTech vaccines.
Estimate the effectiveness and comparative effectiveness of booster vaccination with bivalent original/omicron BA.1 mRNA-1273 (Moderna) and original/omicron BA.1 BNT162b2 (Pfizer-BioNTech) against COVID-19 hospitalisation and death in adults aged ≥50 years.
Design:
Matched cohort studies emulating target trials.
Setting:
With approval of NHS England, we analysed linked primary care, hospital, and COVID-19 surveillance records available within the OpenSAFELY-TPP research platform.
Participants:
For comparison of boosting with no boosting, 3,464,877 adults eligible for booster vaccination during the autumn 2022 UK COVID-19 vaccine rollout, registered with a general practice using the TPP SystmOne clinical information system in England. For the between-vaccine comparison 531,129 boosted pairs.
Interventions:
Vaccination with bivalent BA.1 mRNA-1273 or BNT162b2.
Main outcome measures:
COVID-19-related hospital admission or death, non-COVID-19 death, fracture (negative control outcome).
Results:
In approximately 2.5-million person-years follow up there were 14,436 COVID-19-related hospital admissions, 1,152 COVID-19-related deaths, 32,184 non-COVID-19 deaths, and 52,758 fractures. The 350-day risks/1000 of COVID-19 hospitalisation and COVID-19 death were 3.78 (95% CI 3.65-3.91) and 0.29 (0.26, 0.33) respectively after boosting and 6.81 (6.65-6.98) and 0.61 (0.56, 0.66) without boosting. Over 350 days’ follow-up, adjusted hazard ratios were: COVID-19 hospitalisation 0.51 (95% CI 0.50, 0.53); COVID-19 death 0.45 (0.40, 0.51); non-COVID-19 death 0.56 (0.55, 0.58) and fracture 0.89 (0.87, 0.91). Booster effectiveness waned over time, with greatest effectiveness in the first 70 days after vaccination. The 350-day risks of COVID-19 hospitalisation, COVID-19 death and fracture were similar for the two vaccine brands but higher in the bivalent mRNA-1273 group for non-COVID-19 death (risk difference per 1000 0.88 [0.35, 1.40]).
Conclusions:
Rates of COVID-19-related hospitalisation and death were substantially lower after bivalent original/omicron BA.1 mRNA booster vaccine than in people who remained unboosted. Apparent protection against fracture suggests some unmeasured confounding. Outcomes appeared similar for the Moderna and Pfizer-BioNTech vaccines.
| Original language | English |
|---|---|
| Journal | Vaccine |
| Publication status | Accepted/In press - 20 Jan 2026 |
Keywords
- BNT162b2
- COVID-19
- mRNA-1273
- Omicron variant
- OpenSAFELY
- Vaccine effectiveness
