Comparative effectiveness of BNT162b2 versus mRNA-1273 boosting in England: a cohort study in OpenSAFELY-TPP

Abstract

Introduction The COVID-19 booster vaccination programme in England used both BNT162b2 and mRNA-1273 vaccines. Direct comparisons of the effectiveness against severe COVID-19 of these two vaccines for boosting have not been made in trials or observational data. Methods On behalf of NHS England, we used the OpenSAFELY-TPP database to match adult recipients of each vaccine type on date of vaccination, primary vaccine course, age, and other characteristics. Recipients were eligible if boosted between 29 October 2021 and 31 January 2022, and followed up for 12 weeks. Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death. We estimated the cumulative incidence of each outcome, and quantified comparative effectiveness using risk differences (RD) and hazard ratios (HRs). Results 1,528,431 people were matched in each group, contributing a total 23,150,504 person-weeks of follow-up. The 12-week risks per 1,000 people of positive SARS-CoV-2 test were 103.2 (95%CI 102.4 to 104.0) for BNT162b2 and 96.0 (95.2 to 96.8) for mRNA-1273: the HR comparing mRNA-1273 with BNT162b2 was 0.92 (95%CI 0.91 to 0.92). For COVID-19 hospitalisations the 12-week risks per 1,000 were 0.65 (95%CI 0.56 to 0.75) and 0.44 (0.36 to 0.54): HR 0.67 (95%CI 0.58 to 0.78). COVID-19 deaths were rare: the 12-week risks per 1,000 were 0.03 (95%CI 0.02 to 0.06) and 0.01 (0.01 to 0.02): HR 1.23 (95%CI 0.59 to 2.56). Comparative effectiveness was generally similar within subgroups. Conclusion Booster vaccination with mRNA-1273 COVID-19 vaccine was more effective than BNT162b2 in preventing SARS-CoV-2 infection and COVID-19 hospitalisation during the first 12 weeks after vaccination.

Impact of Differential Vaccine Effectiveness on COVID-19 Hospitalization Cases: Projections for 10 Developed Countries where Booster Vaccines were Recommended

“…This study aimed to build upon Maschio et al by using historical data from the Omicron period, as well as incorporating recently published data into effectiveness estimates. Although the effectiveness data represent a mixture of the Delta and Omicron variants, Hulme et al 4 is one of the few publications that presents a controlled comparison of mRNA-1273 and BNT162b2 in the general population during the Omicron wave. Results from Hulme et al are consistent with other studies published during the Delta and Omicron periods.…”

“…Booster VE against hospitalization for BNT162b2 and Ad26.COV2.S were obtained from Pratama et al, 2022. 15 Similar to booster VE against infection, the HR from Hulme et al, 2022 4 for hospitalizations was applied the BNT162b2 booster hospitalization VE to obtain the VE of mRNA-1273. Data for ChAdOx1-S were unavailable from the Pratama meta-analysis.…”

“…As the purpose of the analysis was to estimate the impact of the difference in VE noted by Hulme et al, 2022, the booster waning rates for mRNA-1273 were adjusted to maintain the HRs from this study for the entire 6-month duration. 4 Sensitivity analyses on the effectiveness of mRNA-1273 were performed by varying the HRs estimated by Hulme et al using the 95% confidence intervals (CI). Using the lower bound yields estimates of VE against infection and hospitalization of 71.6% (waning 5.4%) and 93.6% (waning 1.58%), respectively.…”

“…Real world evidence of the VE against Omicron are now available from studies with large sample sizes and meta-analyses. 4,5,6,7 Butt et al 5 used a retrospective cohort matched study design to assess the VE of an mRNA-based booster dose compared to the primary series among members of the Veteran's Affairs healthcare system (median age 72 years), who are at high risk of infection and adverse outcomes from COVID-19. Ono et al 7 conducted a study of comparative effectiveness between Japanese residents aged ≥16 years who received the BNT162b2 primary series and either a mRNA-1273 or BNT162b2 booster dose; due to data availability, they were unable to adjust for known risk factors for COVID-19.…”

“…Given the small proportion of doses of Ad26.COV2.S delivered globally as a booster, data were unavailable, and were approximated by calculating the ratio between Ad26.COV2.S primary series infection to hospitalization VEs and applying it to Ad26.COV2.S booster hospitalization VE.Booster VE against hospitalization for BNT162b2 and Ad26.COV2.S were obtained from Pratama et al, 2022 15. Similar to booster VE against infection, the HR from Hulme et al, 20224 for hospitalizations was applied the BNT162b2 booster hospitalization VE to obtain the VE of mRNA-1273. Data for ChAdOx1-S were unavailable from the Pratama meta-analysis.…”