Abstract
The SARS-CoV-2 virus spreading across the United States has led to surges of COVID-19 hospitalizations and death. It is clear that randomized trials of single drugs will fail to resolve the crisis due to the complex and multifaceted nature of COVID-19 illness including viral mediated organ damage, cytokine storm, and thrombosis. Patients endure long untreated periods before succumbing to hospitalization and delayed treatment. Thus, early innovative, sequenced multidrug regimens have the best chance of success and are prudent as the next direction in randomized trials and advanced practice. Early management includes: 1) environmental efforts to reduce reinoculation and maintain isolation in the home, 2) combination anti-infective therapy, 3) corticosteroids, 4) antiplatelet agents/antithrombotics, 5) supportive care including supplemental oxygen, monitoring, and telemedicine. Randomized trials of novel oral therapies have not delivered tools of physicians to combat the pandemic in practice. Thus, an immediate pivot from single drug to innovative sequenced multidrug regimens is required as the only strategy to deal with current acute cases of COVID-19 with the aim of avoiding hospitalization and death.