TICO (Therapeutics for Inpatients with COVID-19) is a master protocol to evaluate the safety and efficacy of multiple investigational agents aimed at modifying the host immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, or directly enhancing viral control in order to limit disease progression.

ACTIV-4a (Acute/Inpatient) is a randomized, open label, adaptive platform trial to compare the effectiveness and safety of different antithrombotic strategies for prevention of adverse outcomes in COVID-19 positive inpatients, including specific under-represented minority populations. The study aims to: determine the most effective antithrombotic strategy on the composite endpoint of death, deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, or other systemic arterial thrombosis; for increasing the days free of organ support and reducing death; to assess the safety through the major endpoint of major bleeding; to compare strategies on the endpoint of all-cause mortality.

The overarching goal of this project is to confirm or refute the role of passive immunization as a safe and efficacious therapy in preventing the progression from mild to severe/critical COVID-19 illness and to understand the immunologic kinetics of anti-SARS-CoV-2 antibodies after passive immunization.The primary objective is to determine the efficacy and safety of a single dose of convalescent plasma (CP) for preventing the progression from mild to severe COVID-19 illness. The secondary objective is to characterize the immunologic response to CP administration.

The COVID-19 Outpatient Thrombosis Prevention Trial is a multi-center adaptive randomized double-blind placebo-controlled platform trial to compare the effectiveness of anti-coagulation with anti-platelet agents and with placebo to prevent thrombotic events in patients diagnosed with COVID-19 who have evidence of increased inflammation based on elevated D-dimer and hsCRP levels, yet are not admitted to hospital as COVID-19 related symptoms are currently stable. Participants will all be adults between 40 and 79 years who will be enrolled from approximately 100 facilities, such as emergency rooms and other settings where a physician is present to evaluate the patient for inclusion and exclusion criteria.