Pathophysiological Basis and Rationale for Early Outpatient Treatment of SARS-CoV-2 (COVID-19) Infection.

Approximately 9 months of the SARS-CoV-2 virus spreading across the globe has led to widespread COVID-19 acute hospitalizations and death. The rapidity and highly communicable nature of the SARS-CoV-2 outbreak has hampered the design and execution of definitive randomized, controlled trials of therapy outside of the clinic or hospital. In the absence of clinical trial results, physicians must use what has been learned about the pathophysiology of SARS-CoV-2 infection in determining early outpatient treatment of the illness with the aim of preventing hospitalization or death. This paper outlines key pathophysiological principles that relate to the patient with early infection treated at home. Therapeutic approaches based on these principles include: 1) reduction of reinoculation, 2) combination antiviral therapy, 3) immunomodulation, 4) antiplatelet/antithrombotic therapy 5) administration of oxygen, monitoring, and telemedicine. Future randomized trials testing the principles and agents discussed in this paper will undoubtedly refine and clarify their individual roles, however we emphasize the immediate need for management guidance in the setting of widespread hospital resource consumption, morbidity, and mortality.