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...