Risk factors for SARS-CoV-2 infection after primary vaccination with ChAdOx1 nCoV-19 or BNT162b2 and after booster vaccination with BNT162b2 or mRNA-1273: a population-based cohort study (COVIDENCE UK)

Background: Little is known about how demographic, behavioural, and vaccine-related factors affect risk of post-vaccination SARS-CoV-2 infection. We aimed to identify risk factors for SARS-CoV-2 infection after primary and booster vaccinations. Methods: This prospective, population-based, UK study in adults (≥16 years) vaccinated against SARS-CoV-2 assessed risk of breakthrough SARS-CoV-2 infection up to February, 2022, for participants who completed a primary vaccination course (ChAdOx1 nCoV-19 or BNT162b2) and those who received a booster dose (BNT162b2 or mRNA-1273). Cox regression models explored associations between sociodemographic, behavioural, clinical, pharmacological, and nutritional factors and test-positive breakthrough infection, adjusted for local weekly SARS-CoV-2 incidence. Findings: 1051 (7·1%) of 14 713 post-primary participants and 1009 (9·5%) of 10 665 post-booster participants reported breakthrough infection, over a median follow-up of 203 days (IQR 195–216) and 85 days (66–103), respectively. Primary vaccination with ChAdOx1 (vs BNT162b2) was associated with higher risk of infection in both post-primary analysis (adjusted hazard ratio 1·63, 95% CI 1·41–1·88) and after an mRNA-1273 booster (1·26 [1·00–1·57] vs BNT162b2 primary and booster). Lower risk of infection was associated with older age (post-primary: 0·97 [0·96–0·97] per year; post-booster: 0·97 [0·97–0·98]), whereas higher risk of infection was associated with lower educational attainment (post-primary: 1·78 [1·44–2·20] for primary/secondary vs postgraduate; post-booster: 1·46 [1·16–1·83]) and at least three weekly visits to indoor public places (post-primary: 1·36 [1·13–1·63] vs none; post-booster: 1·29 [1·07–1·56]). Interpretation: Vaccine type, socioeconomic status, age, and behaviours affect risk of breakthrough infection after primary and booster vaccinations. Funding: Barts Charity, UK Research and Innovation Industrial Strategy Challenge Fund.