SARS-COV-2 Screening in Dialysis Facilities: Building an Optimal Strategy to Protect High Risk Populations

项目摘要 接受透析的患者是感染SARS-CoV-2的严重疾病的最高风险群体之一。在 除了在室内设施内进行透析的固有风险外，接受透析的患者 可能是老年人，非白人，来自弱势背景，对病毒的免疫反应受损， 感染和疫苗。血液透析设施提供的通用测试可以保护这种脆弱的 使受感染者能够及早识别和治疗，并减少传播 其他病人和家属。在我们的初步工作中，我们建立了学术界和工业界的伙伴关系， 与美国第三大透析供应商（US Renal Care）和一家中心商业实验室（Ascend 临床）。我们评估了SARS-CoV-2血清阳性率，对感染和疫苗接种的反应，以及疫苗 接受透析患者的可接受性。我们现在提议在这一伙伴关系的基础上， 在透析设施中比较两种基于测试的通用筛查策略，并评估疫苗 有效性在一项实用的群集随机对照试验中，我们将随机选择62家美国肾脏护理机构 估计有2480名患者接受静态与动态通用筛查测试策略。静态通用 筛查将包括每两周为患者提供SARS-CoV-2筛查测试;动态通用 筛查策略将改变测试频率，从每周一次到每四周一次， 取决于社区COVID-19病例率。我们假设在设施中进行透析的患者随机 对社区病例率作出响应的动态测试频率将具有更高的测试可接受性（初级 结果），COVID-19死亡率和住院率较低，并报告更好的护理体验 指标.由于接受透析的患者在流感、肝炎、 B，以及COVID-19疫苗接种，我们将嵌入对COVID-19临床有效性的评估 在这种务实的干预框架内进行疫苗接种。我们将确定无症状和 接种疫苗与未接种疫苗患者的症状性SARS-CoV-2感染，以及疫苗接种的风险因素 突破，特别是ESKD持续时间是否较长以及半定量缺失或减少 受体结合域IgG应答增加突破性感染的风险。我们 网络将处于有利地位，以快速生成关于基于测试的可接受性和益处的数据。 筛查，并将为SARS-CoV-2预防政策提供信息，包括疫苗的潜在修改 剂量和/或制剂。我们的工作目标与RADx-UP计划的目标一致。在 我们将与一个主要的社区利益相关者合作，为这一医疗弱势群体提供服务， 两个最大的公共卫生问题-普遍筛查战略和疫苗评估， 降低接受透析患者的SARS-CoV-2感染、发病率和死亡率风险。

PROJECT ABSTRACT Patients receiving dialysis are one of the highest risk groups for serious illness with SARS-CoV-2 infection. In addition to the inherent risks of travel to and dialysis within indoor facilities, patients receiving dialysis are more likely to be older, non-white, from disadvantaged backgrounds, and have impaired immune responses to viral infections and vaccinations. Universal testing offered at hemodialysis facilities could shield this vulnerable population from exposure, enable early identification and treatment for those affected, and reduce transmission to other patients and family members. In our preliminary work, we created an academic-industry partnership with the third largest dialysis provider in the US (US Renal Care) and a central commercial laboratory (Ascend Clinical). We evaluated SARS-CoV-2 seroprevalence, response to infection and vaccination, and vaccine acceptability among patients receiving dialysis. We now propose to build on this partnership to implement and compare two test-based universal screening strategies in dialysis facilities, and to assess vaccine effectiveness. In a pragmatic cluster randomized controlled trial, we will randomize 62 US Renal Care facilities with an estimated 2480 patients to static versus dynamic universal screening testing strategies. Static universal screening will involve offering patients SARS-CoV-2 screening tests every two weeks; the dynamic universal screening strategy will vary the frequency of testing from once every week to once every four weeks, depending on community COVID-19 case rates. We hypothesize that patients dialyzing at facilities randomized to a dynamic testing frequency responsive to community case rates will have higher test acceptability (primary outcome), experience lower rates of COVID-19 death and hospitalization, and report better experience-of-care metrics. Since patients receiving dialysis achieve suboptimal rates of seroconversion post influenza, hepatitis B, and COVID-19 vaccination, we will embed an assessment of the clinical effectiveness of COVID-19 vaccination within the framework of this pragmatic intervention. We will determine rates of asymptomatic and symptomatic SARS-CoV-2 infection in vaccinated versus unvaccinated patients, and risk factors for vaccine breakthrough, specifically whether longer duration of ESKD and absent or diminished semi-quantitative receptor binding domain IgG response one-year post vaccination increase risk for breakthrough infection. Our network will be well-positioned to rapidly generate data on the acceptability and benefits of test-based screening, and will inform policies for SARS-CoV-2 prevention including potential modification of vaccine dosing and/or formulations. The objectives of our work align with the goals of the RADx-UP initiative. In collaboration with a major community stakeholder serving this medically vulnerable population, we will address two issues of utmost public health concern—universal screening strategies and vaccine assessments—and reduce risks for SARS-CoV-2 infection, morbidity, and mortality in patients receiving dialysis.