Post-vaccination SARS-CoV-2 infection: risk factors and illness profile in a prospective, observational community-based case-control study

Antonelli, M.; Penfold, R. S.; Merino, J.; Sudre, C. H.; Molteni, E.; Berry, S.; Canas, L. S.; Graham, M. S.; Klaser, K.; Modat, M.; Murray, B.; Österdahl, M. F.; Cheetham, N. J.; Drew, D. A.; Nguyen, L. A.; Capdeila, J.; Hu, C.; Selvachandran, S.; Polidori, L.; May, A.; Wolf, J.; Chan, A. T.; Hammers, A.; Duncan, E.; Spector, T.; Ourselin, S.; Steves, C. J.

Background: Both BNT162b2 and ChAdOx1 vaccines show good efficacy in clinical trials and real-world data. However, some still contract SARS-CoV-2 post-vaccination. This study identifies risk factors associated with SARS-CoV-2 infection at least 14 days after first vaccination and describes characteristics of post-vaccination illness. Methods: Cases were UK adults reporting post-vaccination SARS-CoV-2 infection between 8th December 2020 and 1st May 2021, reporting on the COVID Symptom Study app. We assessed the associations of age, frailty, comorbidity, area-level deprivation and lifestyle factors with infection (vaccinated cases vs. negative-vaccinated controls); and vaccination with illness profile (vaccinated cases vs positive-unvaccinated controls). Findings: Post-vaccination infection risk was substantially higher in older adults with frailty (OR= 2.78, 95% CI [1.98-3.89], p-value<0.0001) and in individuals living in most deprived areas (OR vs. intermediate group=1.22, 95%CI [1.04-1.43], p-value=0.01). Risk was lower in individuals with a healthier diet (OR=0.73, 95%CI [0.62-0.86], p-value<0.0001) and without obesity (OR=0.6, 95% CI [0.44-0.82], p-value=0.001). Vaccination was associated with reduced odds of hospitalisation (OR=0.36, 95%CI [0.28-0.46], p-value<0.0001), and high acute-symptom burden (OR=0.51, 95%CI [0.42-0.61], p-value<0.0001). In the 60+ age group, risk of >28 days illness was lower following vaccination (OR=0.72 , 95%CI [0.51-1.00], p-value=0.05). Most symptoms were reported less in positive-vaccinated vs. positive-unvaccinated individuals, except sneezing, which was more common post-vaccination (OR=1.24, 95%CI [1.05-1.46], p-value=0.01). Interpretation: Our findings highlight reduced symptom burden and duration in those infected post-vaccination. Whilst reassuring, our data should prompt efforts to boost vaccine effectiveness in at-risk populations; moreover, targeted infection control measures will still be appropriate to minimise SARS-CoV-2 infection.