Abstract This supplement will support ACTIV-2D ACTIV-2D is a master protocol to evaluate the safety and efficacy of investigational agents for the treatment of symptomatic non-hospitalized adults with SARS-CoV-2 infection. The protocol is a phase III multicenter, randomized, double blind trial to evaluate the safety and efficacy of S-217622 for the treatment of symptomatic high-risk non-hospitalized adults with SARS-CoV-2 infection. The primary outcome is to determine if the investigational agent (S-217622) will prevent the composite endpoint of hospitalization due to any cause or death due to any cause through study Day 29. Hospitalization is defined as ≥24 hours of acute care, in a hospital or similar acute care facility, including Emergency Rooms or temporary facilities instituted to address medical needs of those with severe coronavirus disease 2019 (COVID-19) during the COVID-19 pandemic.