Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study
Parker EPK., Horne EMF., Hulme WJ., Tazare J., Zheng B., Carr EJ., Loud F., Lyon S., Mahalingasivam V., MacKenna B., Mehrkar A., Scanlon M., Santhakumaran S., Steenkamp R., Goldacre B., Sterne JAC., Nitsch D., Tomlinson LA.
Background: Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England. Methods: With the approval of NHS England, we performed a retrospective cohort study among people with moderate-to-severe kidney disease. Using linked primary care and UK Renal Registry records in the OpenSAFELY-TPP platform, we identified adults with stage 3–5 chronic kidney disease, dialysis recipients, and kidney transplant recipients. We used Cox proportional hazards models to compare COVID-19-related outcomes and non-COVID-19 death after two-dose (AZ–AZ vs BNT–BNT) and three-dose (AZ–AZ–BNT vs BNT–BNT–BNT) schedules. Findings: After two doses, incidence during the Delta wave was higher in AZ–AZ (n = 257,580) than BNT–BNT recipients (n = 169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37–1.50], 1.59 [1.43–1.77], 1.44 [1.12–1.85], and 1.09 [1.02–1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ–AZ–BNT (n = 220,330) and BNT–BNT–BNT recipients (n = 157,065) for any outcome during a period of Omicron dominance. Interpretation: Among individuals with moderate-to-severe kidney disease, two doses of BNT conferred stronger protection than AZ against SARS-CoV-2 infection and severe disease. A subsequent BNT dose levelled the playing field, emphasising the value of heterologous RNA doses in vulnerable populations. Funding: National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.