The primary objective of this supplemental application is to rapidly enhance the ability of the two domestic CRSs in the Case Clinical Trials Unit to enroll and follow participants in COVID-19 prevention and treatment trials, with a particular emphasis on enhancing the sites’ capacity to collect, process, store, and ship longitudinal biological specimens from these participants at any stage of the disease process. The following specific aims are proposed to accomplish this objective: Specific aim 1: To expand CRS capacity to identify new SARS-CoV-2 infections and to offer participation in clinical trials and observational studies. A key element to contribute meaningfully to prevention and treatment trials will be to have access to recently diagnosed persons with SARS-CoV-2 infection who can be offered participation. Here, we will enhance the capacity of the two CRSs to access these potential participants by establishing partnerships with central laboratory leadership and expanding support for research staff who can support expanded testing and offer participation in research early after diagnosis. Specific aim 2: To improve CRS infrastructure to facilitate specimen collection and longitudinal follow- up of SARS-CoV-2 infected study participants. Among the challenges to refashion the CRSs to conduct COVID-19 trials are limitations in access to secure facilities and personal protection equipment. To address this, dedicated protective enclosures will be established at the Case CRS, and dedicated PPE will be acquired where needed for the duration of this funding period, which will be the critical interval during which supply bottlenecks are anticipated to persist. Specific aim 3: To enhance participation of at-risk and SARS-CoV-2-infected persons in clinical research protocols. Recruitment of at-risk and infected participants into COVID-19 trials will require novel strategies to reach out into the community, and to engage potential participants into clinical research despite no existing connection to the CRSs. To overcome these obstacles, we will devote dedicated effort from outreach coordinators specifically to COVID-19 recruitment, and establish online advertisement campaigns to maximize opportunities for enrollment. Specific aim 4: To increase CRS capacity for processing and storage of biological specimens from COVID- 19 research participants. The final barrier to processing, storing, and archiving specimens from COVID-19 prevention and treatment clinical trials is the need for enhanced biosafety precautions in the processing laboratory. At both CRSs, enhanced BSL-2 workstations will be established, with dedicated equipment when needed, to increase the ability to process efficiently specimens derived from COVID-19 trials.