Comparative effectiveness of different primary vaccination courses on mRNA based booster vaccines against SARs-COV-2 infections: A time-varying cohort analysis using trial emulation in the Virus Watch community cohort (preprint)

ABSTRACT

Abstract Importance The Omicron (B.1.1.529) variant has increased SARs-CoV-2 infections in double vaccinated individuals globally, particularly in ChAdOx1 recipients. To tackle rising infections, the UK accelerated booster vaccination programmes used mRNA vaccines irrespective of an individual's primary course vaccine type with booster doses rolled out according to clinical priority. There is limited understanding of the effectiveness of different primary vaccination courses on mRNA based booster vaccines against SARs-COV-2 infections and how time-varying confounders can impact the evaluations comparing different vaccines as primary courses for mRNA boosters. Objective To evaluate the comparative effectiveness of ChAdOx1 versus BNT162b2 as primary doses against SARs-CoV-2 in booster vaccine recipients whilst accounting for time-varying confounders. Design Trial emulation was used to reduce time-varying confounding-by-indication driven by prioritising booster vaccines based upon age, vulnerability and exposure status e.g. healthcare worker. Trial emulation was conducted by meta-analysing eight cohort results whose booster vaccinations were staggered between 16/09/2021 to 05/01/2022 and followed until 23/01/2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end-of-study was modelled using Cox proportional hazards models for each cohort and adjusted for age, sex, minority ethnic status, clinically vulnerability, and deprivation. Setting Prospective observational study using the Virus Watch community cohort in England and Wales. Participants People over the age of 18 years who had their booster vaccination between 16/09/2021 to 05/01/2022 without prior natural immunity. Exposures ChAdOx1 versus BNT162b2 as a primary dose, and an mRNA booster vaccine. Results Across eight cohorts, 19,692 mRNA vaccine boosted participants were analysed with 12,036 ChAdOx1 and 7,656 BNT162b2 primary courses with a median follow-up time of 73 days (IQR54-90). Median age, clinical vulnerability status and infection rates fluctuate through time. 7.2% (n=864) of boosted adults with ChAdOx1 primary course experienced a SARS-CoV-2 infection compared to 7.6% (n=582) of those with BNT162b2 primary course during follow-up. The pooled adjusted hazard ratio was 0.99 [95%CI0.88-1.11], demonstrating no difference between the incidence of SARs-CoV-2 infections based upon the primary vaccine course. Conclusion and Relevance In mRNA boosted individuals, we found no difference in protection comparing those with a primary course of BNT162b2 to those with aChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection.