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. 2023 May 3:30:100636.
doi: 10.1016/j.lanepe.2023.100636. Online ahead of print.

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

OpenSAFELY Collaborative; Edward P K Parker  1 , Elsie M F Horne  2   3 , William J Hulme  4 , John Tazare  1 , Bang Zheng  1 , Edward J Carr  5 , Fiona Loud  6 , Susan Lyon  7 , Viyaasan Mahalingasivam  1 , Brian MacKenna  4 , Amir Mehrkar  4 , Miranda Scanlon  8 , Shalini Santhakumaran  9 , Retha Steenkamp  9 , Ben Goldacre  2 , Jonathan A C Sterne  2   3   10 , Dorothea Nitsch  1   9 , Laurie A Tomlinson  1 ; LH&W NCS (or CONVALESCENCE) Collaborative
Affiliations

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

OpenSAFELY Collaborative et al. Lancet Reg Health Eur. .

Abstract

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.

Keywords: COVID-19; Chronic kidney disease; Effectiveness; NHS England; SARS-CoV-2; Vaccination.

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Conflict of interest statement

EPKP has been employed as a consultant by the WHO Strategic Advisory Group of Experts on Immunization Working Group on COVID-19 Vaccines. WJH and VM have received research funding from the National Institute for Health and Care Research (NIHR). EJC has received research funding (paid to the institution) form Kidney Research UK and partner charities and patient associations. FL is employed as Policy Director of Kidney Care UK, which has received funding from AstraZeneca, Pfizer, Novartis, and GSK, and honoraria (paid to the institution) from AstraZeneca, Novartis, and University College London for invited talks and meeting attendance. FL is Lay Chair of the West Herts Hospital Organ Donation committee; Vice Chair of the Lister Hospital Kidney Patients’ Association; and member of the International Society for Nephrology patient liaison advisory group. SL has received medical writing fees from the UK Kidney Association and Vascular Society of Great Britain and Ireland; freelance employment as Deputy Editor for Kidney Care UK's Kidney Matters magazine; and support for conference attendance from the UK Kidney Association. SL is Chair of the UK Kidney Association Patient Council and member of the Guy’s and St Thomas’ Kidney Patients’ Association. BMK is also employed by NHS England as a specialist pharmacist adviser. AM has received consultancy fees from Induction Healthcare and is a member of the Royal College of General Practitioners’ health informatics group and the NHS Digital GP data Professional Advisory Group. BG’s work on better use of data in healthcare more broadly is currently funded in part by: the Bennett Foundation, the Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation; all Bennett Institute staff are supported by BG’s grants on this work. BG is a Non-Executive Director at NHS Digital. DN is the UK Kidney Association's Director of Informatics Research. LAT has received research funding from the Medical Research Council (MRC), Wellcome, and NIHR; has consulted for Bayer in relation to an observational study of chronic kidney disease (unpaid); is a member of four non-industry funded (NIHR/MRC) trial advisory committees (unpaid); and is a member of the Medicines and Healthcare products Regulatory Agency expert advisory group (Women’s Health). The authors disclose no other competing interests.

Figures

Fig. 1
Fig. 1
Cumulative incidence rates by vaccine group. Kaplan–Meier estimates of cumulative incidence in matched two-dose and three-dose sub-cohorts. Kaplan–Meier steps are delayed until ≥5 events occur in compliance with re-identification minimisation requirements in OpenSAFELY. Data for the matched sub-cohorts are shown here to minimise confounding associated with key matching variables; see Supplementary Fig. S2 for equivalent plots relating to the unmatched cohorts. Numbers at risk at days 0, 15, 71, and 127 are provided in Supplementary Tables S8 (two-dose cohort) and S10 (three-dose cohort). AZ, AZD1222 (AstraZeneca); BNT, BNT162b2 (Pfizer/BioNTech).
Fig. 2
Fig. 2
Hazard ratios for the comparative effectiveness of two- and three-dose schedules in kidney disease subgroups. See Supplementary Tables S9 (two-dose cohort) and S11 (three-dose cohort) for associated population sizes and incidence rates. AZ, AZD1222; BNT, BNT162b2; CI, confidence interval; CKD, chronic kidney disease; [R], redacted due to low event counts in one or both vaccine groups; RRT, renal replacement therapy.
Fig. 3
Fig. 3
Hazard ratios for the comparative effectiveness of two- and three-dose schedules. See Supplementary Tables S8 (two-dose cohort) and S10 (three-dose cohort) for associated population sizes and incidence rates. AZ, AZD1222; BNT, BNT162b2; CI, confidence interval; [R], redacted due to low event counts in one or more groups.
See this image and copyright information in PMC

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