RESUMO
BackgroundKidney 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. MethodsWith the approval of NHS England, we performed a retrospective cohort study to estimate the comparative effectiveness of schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with 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. FindingsAfter 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{middle dot}43 [1{middle dot}37-1{middle dot}50], 1{middle dot}59 [1{middle dot}43-1{middle dot}77], 1{middle dot}44 [1{middle dot}12-1{middle dot}85], and 1{middle dot}09 [1{middle dot}02-1{middle dot}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. InterpretationAmong 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. FundingNational Core Studies, Wellcome Trust, MRC, and Health Data Research UK. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Medline for studies published between 1st December 2020 and 7th September 2022 using the following term: "(coronavir* or covid* or sars*) and (vaccin* or immunis* or immuniz*) and (kidney or dialysis or h?emodialysis or transplant or renal) and (efficacy or effectiveness)". We identified studies reporting on the effectiveness of various COVID-19 vaccines in individuals with chronic kidney disease (CKD) or end-stage renal disease. Several studies have reported no clear differences in effectiveness against outcomes of varying severity after two doses of BNT162b2 or AZD1222 compared to unvaccinated controls, which is contrary to the significantly higher antibody levels observed after BNT162b2 in immunogenicity studies. One study also showed that a third dose of RNA vaccine restored some protection against the Omicron variant among BNT162b2- and AZD1222-primed individuals, with no clear differences between these groups. This finding is consistent with immunogenicity data suggesting that a third dose of BNT162b2 may reduce the gap in antibody levels observed after two of AZD1222 versus BNT162b2. Notably, we found few studies directly comparing effectiveness in BNT162b2 versus AZD1222 recipients, which reduces biases associated with comparison to a small and potentially unrepresentative group of unvaccinated controls. We also found no studies exploring COVID-19 vaccine effectiveness in kidney disease groups of varying severity (CKD, dialysis, and kidney transplant). Added value of this studyThis is the largest study to compare the effectiveness of two- and three-dose regimens involving AZD1222 and BNT162b2 among people with moderate-to-severe kidney disease. We compared effectiveness after two and three doses in 426,780 and 377,395 individuals, respectively, and harnessed unique data linkages between primary care records and UK Renal Registry data to identify people with CKD and end-stage renal disease (including dialysis and kidney transplant recipients) with high accuracy. During the Delta wave of infection, we observed a higher risk of COVID-19-related outcomes of varying severity after two doses of AZD1222 versus BNT162b2, with consistent findings in CKD, dialysis, and transplant subgroups. After a third dose of BNT162b2, AZD1222- and BNT162b2-primed individuals had similar rates of COVID-19-related outcomes during a period of Omicron dominance. Implications of all the available evidence A growing body of immunogenicity and effectiveness data - including the present study - suggest that two doses of BNT162b2 confers stronger protection than AZD1222 among people with moderate-to-severe kidney disease. However, a third dose of BNT162b2 appears to compensate for this immunity deficit, providing equivalent protection in BNT162b2- and AZD1222-primed individuals. Achieving high coverage with additional RNA vaccine doses (whether homologous or heterologous) has the capacity to reduce the burden of disease in this vulnerable population.
RESUMO
BackgroundKidney disease is a significant risk factor for COVID-19-related mortality. Achieving high COVID-19 vaccine coverage among people with kidney disease is therefore a public health priority. MethodsWith the approval of NHS England, we performed a retrospective cohort study using the OpenSAFELY-TPP platform. Individual-level routine clinical data from 24 million people in England were included. A cohort of individuals with stage 3-5 chronic kidney disease (CKD) or receiving renal replacement therapy (RRT) at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate or inclusion in the UK Renal Registry. Individual-level factors associated with vaccine uptake were explored via Cox proportional hazards models. Results948,845 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 11th May 2022 was 97.5%, 97.0%, and 93.5% for doses 1, 2, and 3, respectively, and 61.1% among individuals with one or more indications for receipt of a fourth dose. Delayed 3-dose vaccine uptake was associated with non-White ethnicity, social deprivation, and severe mental illness - associations that were consistent across CKD stages and in RRT recipients. Similar associations were observed for 4-dose uptake, which was also delayed among care home residents. ConclusionAlthough high primary and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across demographic groups. Identifying how to address these disparities remains a priority to reduce the risk of severe disease in this vulnerable patient group.
RESUMO
BackgroundThe UK COVID-19 vaccination programme delivered its first "booster" doses in September 2021, initially in groups at high risk of severe disease then across the adult population. The BNT162b2 Pfizer-BioNTech vaccine was used initially, with Moderna mRNA-1273 subsequently also used. MethodsWe used the OpenSAFELY-TPP database, covering 40% of English primary care practices and linked to national coronavirus surveillance, hospital episodes, and death registry data, to estimate the effectiveness of boosting with BNT162b2 compared with no boosting in eligible adults who had received two primary course vaccine doses between 16 September and 16 December 2021 when the Delta variant of SARS-CoV-2 was dominant. Follow up was for up to 10 weeks. Each booster recipient was matched with an unboosted control on factors relating to booster priority status and prior immunisation. Additional factors were adjusted for in Cox models estimating hazard ratios (HRs). Outcomes were positive SARS-CoV-2 test, COVID-19 hospitalisation, COVID-19 death and non-COVID-9 death. Booster vaccine effectiveness was defined as 1-HR. ResultsAmong 4,352,417 BNT162b2 booster recipients matched with unboosted controls, estimated effectiveness of a booster dose compared with two doses only was 50.7% (95% CI 50.1-51.3) for positive SARS-CoV-2 test, 80.1% (78.3-81.8) for COVID-19 hospitalisation, 88.5% (85.0-91.1) for COVID-19 death, and 80.3% (79.0-81.5) for non-COVID-19 death. Estimated effectiveness was similar among those who had received a BNT162b2 or ChAdOx1-S two-dose primary vaccination course, but effectiveness against severe COVID-19 was slightly lower in those classified as clinically extremely vulnerable (76.3% (73.1-79.1) for COVID-19 hospitalisation, and 85.1% (79.6-89.1) for COVID-19 death). Estimated effectiveness against each outcome was lower in those aged 18-65 years than in those aged 65 and over. ConclusionOur findings are consistent with strong protection of BNT162b2 boosting against positive SARS-CoV-2 test, COVID-19 hospitalisation, and COVID-19 death.
RESUMO
BackgroundThe rate at which COVID-19 vaccine effectiveness wanes over time is crucial for vaccination policies, but is incompletely understood with conflicting results from different studies. MethodsThis cohort study, using the OpenSAFELY-TPP database and approved by NHS England, included individuals without prior SARS-CoV-2 infection assigned to vaccines priority groups 2-12 defined by the UK Joint Committee on Vaccination and Immunisation. We compared individuals who had received two doses of BNT162b2 or ChAdOx1 with unvaccinated individuals during six 4-week comparison periods, separately for subgroups aged 65+ years; 16-64 years and clinically vulnerable; 40-64 years and 18-39 years. We used Cox regression, stratified by first dose eligibility and geographical region and controlled for calendar time, to estimate adjusted hazard ratios (aHRs) comparing vaccinated with unvaccinated individuals, and quantified waning vaccine effectiveness as ratios of aHRs per-4-week period. The outcomes were COVID-19 hospitalisation, COVID-19 death, positive SARS-CoV-2 test, and non-COVID-19 death. FindingsThe BNT162b2, ChAdOx1 and unvaccinated groups comprised 1,773,970, 2,961,011 and 2,433,988 individuals, respectively. Waning of vaccine effectiveness was similar across outcomes and vaccine brands: e.g. in the 65+ years subgroup ratios of aHRs versus unvaccinated for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test ranged from 1.23 (95% CI 1.15-1.32) to 1.27 (1.20-1.34) for BNT162b2 and 1.16 (0.98-1.37) to 1.20 (1.14-1.27) for ChAdOx1. Despite waning, rates of COVID-19 hospitalisation and COVID-19 death were substantially lower among vaccinated individuals compared to unvaccinated individuals up to 26 weeks after second dose, with estimated aHRs <0.20 (>80% vaccine effectiveness) for BNT162b2, and <0.26 (>74%) for ChAdOx1. By weeks 23-26, rates of SARS-CoV-2 infection in fully vaccinated individuals were similar to or higher than those in unvaccinated individuals: aHRs ranged from 0.85 (0.78-0.92) to 1.53 (1.07-2.18) for BNT162b2, and 1.21 (1.13-1.30) to 1.99 (1.94-2.05) for ChAdOx1. InterpretationThe rate at which estimated vaccine effectiveness waned was strikingly consistent for COVID-19 hospitalisation, COVID-19 death and positive SARS-CoV-2 test, and similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the Omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination doses.
