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Effectiveness of mRNA COVID-19 Vaccines as First Booster Doses in England: An Observational Study in OpenSAFELY-TPP
Elsie M F Horne1,2, William J Hulme3, Edward P K Parker4
1From the Population Health Sciences, University of Bristol, Oakfield House, Oakfield Grove, Bristol, United Kingdom.
Insights
COVID-19 vaccine boosters significantly reduced hospitalizations and deaths for up to 6 months. However, protection against positive SARS-CoV-2 tests waned, with higher incidence in boosted individuals by 6 months.
Area of Science:
- Immunology
- Epidemiology
- Vaccinology
Background:
- The UK initiated COVID-19 vaccine booster programs in September 2021, prioritizing high-risk individuals before expanding to all adults.
- Initial boosters utilized the Pfizer-BioNTech BNT162b2 vaccine, with the Moderna mRNA-1273 vaccine also being deployed.
Purpose of the Study:
- To evaluate the effectiveness of COVID-19 booster vaccinations (BNT162b2 or mRNA-1273) compared to no booster.
- To assess protection against SARS-CoV-2 infection, COVID-19 hospitalization, COVID-19 death, non-COVID-19 death, and fractures over 6 months.
Main Methods:
- Utilized routine clinical data from NHS England, matching 8,198,643 booster recipients with unboosted controls.
- Employed Cox models to estimate hazard ratios for various outcomes up to 182 days post-booster dose.
- Adjusted for factors including booster priority and prior COVID-19 immunization status.
Main Results:
- Booster vaccination showed significant effectiveness: 25% reduction in positive SARS-CoV-2 tests, 70% in COVID-19 hospitalizations, and 89% in COVID-19 deaths.
- Effectiveness against severe outcomes peaked within 3 months, with cumulative positive SARS-CoV-2 test incidence higher in boosted individuals by 6 months.
- Reduced rates of non-COVID-19 death (78% reduction) and fractures (23% reduction) were observed in boosted individuals.
Conclusions:
- COVID-19 boosters provide substantial protection against severe outcomes like hospitalization and death.
- Protection against symptomatic SARS-CoV-2 infection is limited and wanes over 6 months.
- Observed lower fracture rates in boosted individuals suggest potential unmeasured confounding, highlighting the need for careful interpretation of observational data.
Background:
The UK delivered its first "booster" COVID-19 vaccine doses in September 2021, initially to individuals at high risk of severe disease, then to all adults. The BNT162b2 Pfizer-BioNTech vaccine was used initially, then also Moderna mRNA-1273.
Methods:
With the approval of the National Health Service England, we used routine clinical data to estimate the effectiveness of boosting with BNT162b2 or mRNA-1273 compared with no boosting in eligible adults who had received two primary course vaccine doses. We matched each booster recipient with an unboosted control on factors relating to booster priority status and prior COVID-19 immunization. We adjusted for additional factors in Cox models, estimating hazard ratios up to 182 days (6 months) following booster dose. We estimated hazard ratios overall and within the following periods: 1-14, 15-42, 43-69, 70-97, 98-126, 127-152, and 155-182 days. Outcomes included a positive SARS-CoV-2 test, COVID-19 hospitalization, COVID-19 death, non-COVID-19 death, and fracture.
Results:
We matched 8,198,643 booster recipients with unboosted controls. Adjusted hazard ratios over 6-month follow-up were: positive SARS-CoV-2 test 0.75 (0.74, 0.75); COVID-19 hospitalization 0.30 (0.29, 0.31); COVID-19 death 0.11 (0.10, 0.14); non-COVID-19 death 0.22 (0.21, 0.23); and fracture 0.77 (0.75, 0.78). Estimated effectiveness of booster vaccines against severe COVID-19-related outcomes peaked during the first 3 months following the booster dose. By 6 months, the cumulative incidence of positive SARS-CoV-2 test was higher in boosted than unboosted individuals.
Conclusions:
We estimate that COVID-19 booster vaccination, compared with no booster vaccination, provided substantial protection against COVID-19 hospitalization and COVID-19 death but only limited protection against positive SARS-CoV-2 test. Lower rates of fracture in boosted than unboosted individuals may suggest unmeasured confounding. Observational studies should report estimated vaccine effectiveness against nontarget and negative control outcomes.
