Yanev Ivan, Gagnon Michael, Cheng Matthew P, Paraskevas Steven, Kumar Deepali, Dragomir Alice, Sapir-Pichhadze Ruth
Centre for Outcomes Research and Evaluation, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Division of Nephrology and Multi-Organ Transplant Program, Department of Medicine, McGill University, Montreal, QC, Canada.
Can J Kidney Health Dis. 2021 Sep 14;8:20543581211040332. doi: 10.1177/20543581211040332. eCollection 2021.
The coronavirus disease 2019 (COVID-19) pandemic impacted transplant programs across Canada.
We evaluated the implications of delays in transplantation among Canadian end-stage kidney disease (ESKD) patients to allow pretransplant vaccination.
We used a Markov microsimulation model and ESKD patient perspective to study the effectiveness (quality-adjusted life years [QALY]) of living (LD) or deceased donor (DD) kidney transplantation followed by 2-dose SARS-CoV-2 vaccine versus delay in LD ("Delay LD") or refusal of DD offer ("Delay DD") to receive 2-dose SARS-CoV-2 vaccine pretransplant.
Canadian dialysis and transplant centers.
We simulated a 10 000-waitlisted ESKD patient cohort, which was predictively modeled for a lifetime horizon in monthly cycles.
Inputs on patient and graft survival estimates by patient, LD or DD characteristics, were extracted from the Treatment of End-Stage Organ Failure in Canada, Canadian Organ Replacement Register, 2009 to 2018. In addition, a literature review provided inputs on quality of life, SARS-CoV-2 transmissibility, new variants of concern, mortality risk, and antibody responses to 2-dose SARS-CoV-2 mRNA vaccines.
We conducted base case, scenario, and sensitivity analyses to illustrate the impact of patient, donor, vaccine, and pandemic characteristics on the preferred strategy.
In the average waitlisted Canadian patient, receiving 2-dose SARS-CoV-2 vaccine post-transplant provided an effectiveness of 22.32 (95% confidence interval: 22.00-22.7) for LD and 19.34 (19.02-19.67) QALYs for DD. Delaying transplants for 6 months to allow 2-dose SARS-CoV-2 vaccine before LD and DD transplant yielded effectiveness of 22.83 (21.51-23.14) and 20.65 (20.33-20.96) QALYs, respectively. Scenario analysis suggested a benefit to short delays in DD transplants to receive 2-dose SARS-CoV-2 vaccine in waitlisted patients ≥55 years. Two-way sensitivity analysis suggested decreased effectiveness of the strategy prioritizing 2-dose SARS-CoV-2 vaccine prior to DD transplant the longer the delay and the higher the Kidney Donor Risk Index of the eventual DD transplant. When assessing the impact of SARS-CoV-2 variants of concern (infection rates ≥10-fold and associated mortality ≥3-fold vs base case), we found short delays to allow 2-dose SARS-CoV-2 vaccine administration pretransplant to be preferable.
Risks associated with nosocomial exposure of LDs were not considered. There was uncertainty regarding input parameters related to SARS-CoV-2 infection, new variants, and COVID-19 severity in ESKD patients. Given rollout of population-level SARS-CoV-2 vaccination, we assumed a linear decrease in infection rates over 1 year. Proportions of patients mounting an antibody response to 2-dose SARS-CoV-2 mRNA vaccines were considered in lieu of data on vaccine efficacy in dialysis and following transplantation. Non-age-stratified annual mortality rates were used for waitlisted candidates.
Our analyses suggest that short delays allowing pretransplant vaccination offered comparable to greater effectiveness than pursuing transplantation without delay, proposing transplant candidates should be prioritized to receive at least 2 doses of SARS-CoV-2 vaccine. Our scenario and sensitivity analyses suggest that caution must be exercised when declining DD offers in patients offered low risk DD and who are likely to incur significant delays in access to transplantation. While population-level herd immunity may decrease infection risk in transplant patients, more data are required on vaccine efficacy against SARS-CoV-2 and variants of concern in ESKD, and how efficacy may be modified by a third vaccine dose, maintenance immunosuppression and timing of induction and rejection therapies.
2019年冠状病毒病（COVID-19）大流行对加拿大各地的移植项目产生了影响。
我们评估了加拿大终末期肾病（ESKD）患者移植延迟以进行移植前疫苗接种的影响。
我们使用马尔可夫微观模拟模型，并从ESKD患者的角度研究活体（LD）或 deceased donor（DD）肾移植，随后接种2剂严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗，与延迟LD（“延迟LD”）或拒绝DD供体提议（“延迟DD”）以在移植前接受2剂SARS-CoV-2疫苗相比的有效性（质量调整生命年[QALY]）。
加拿大透析和移植中心。
我们模拟了一个10000名等待移植的ESKD患者队列，并针对其一生进行了每月周期的预测建模。
根据患者、LD或DD特征对患者和移植物存活估计的输入数据，从2009年至2018年加拿大终末期器官衰竭治疗、加拿大器官替代登记处提取。此外，文献综述提供了关于生活质量、SARS-CoV-2传播性、新的关注变体、死亡风险以及对2剂SARS-CoV-2 mRNA疫苗的抗体反应的输入数据。
我们进行了基础病例、情景和敏感性分析，以说明患者、供体、疫苗和大流行特征对首选策略的影响。
在平均等待移植的加拿大患者中，移植后接种2剂SARS-CoV-2疫苗，LD的有效性为22.32（95%置信区间：22.00 - 22.7），DD为19.34（19.02 - 19.67）QALY。将移植延迟6个月以在LD和DD移植前接种2剂SARS-CoV-2疫苗，有效性分别为22.83（21.51 - 23.14）和20.65（20.33 - 20.96）QALY。情景分析表明，对于≥55岁的等待移植患者，DD移植短期延迟以接种2剂SARS-CoV-2疫苗有好处。双向敏感性分析表明，DD移植前优先接种2剂SARS-CoV-2疫苗的策略，延迟时间越长且最终DD移植的肾脏供体风险指数越高，有效性越低。在评估SARS-CoV-2关注变体的影响（感染率≥10倍且相关死亡率≥3倍与基础病例相比）时，我们发现移植前短期延迟以允许接种2剂SARS-CoV-2疫苗更可取。
未考虑与LD医院暴露相关的风险。与SARS-CoV-2感染、新变体以及ESKD患者中COVID-19严重程度相关的输入参数存在不确定性。鉴于人群层面SARS-CoV-2疫苗的推出，我们假设感染率在1年内呈线性下降。考虑了对2剂SARS-CoV-2 mRNA疫苗产生抗体反应的患者比例，以代替透析和移植后疫苗效力的数据。对等待移植的候选人使用了非年龄分层的年度死亡率。
我们的分析表明，短期延迟以进行移植前疫苗接种提供了与不延迟进行移植相当或更高的有效性，建议应优先安排移植候选人接受至少2剂SARS-CoV-2疫苗。我们的情景和敏感性分析表明，对于提供低风险DD且可能在获得移植方面出现显著延迟的患者，拒绝DD提议时必须谨慎。虽然人群层面的群体免疫可能会降低移植患者的感染风险，但仍需要更多关于ESKD中针对SARS-CoV-2及其关注变体的疫苗效力的数据，以及第三剂疫苗、维持免疫抑制以及诱导和排斥治疗时机如何改变效力的数据。
