Innovative solutions are required to effectively address the unprecedented surge of demand on our healthcare systems created by the COVID-19 pandemic. Home treatment and monitoring of patients who are asymptomatic or mildly symptomatic can be readily implemented to ameliorate the health system burden while maintaining safety and effectiveness of care. Such endeavor requires careful triage and coordination, telemedicine and technology support, workforce and education, as well as robust infrastructure. In the understandable paucity of evidence-based, protocolized approaches toward HOT for COVID-19 patients, our group has created the current document based on the cumulative experience of members of the Joint ACAIM-WACEM COVID-19 Clinical Management Taskforce. Utilizing available evidence-based resources and extensive front-line experience, the authors have suggested a pragmatic pathway for providing safe and effective home oxygen therapy in the community setting.
SARS-CoV-2 utilizes the IMPα/β1 heterodimer to enter host cell nuclei after gaining cellular access through the ACE2 receptor. Ivermectin has shown antiviral activity by inhibiting the formation of the importin-α (IMPα) and IMPβ1 subunits as well as dissociating the IMPα/β1 heterodimer and has in vitro efficacy against SARS-CoV-2. Plasma and lung ivermectin concentrations vs. time profiles in cattle were used to determine the apparent plasma to lung tissue partition coefficient of ivermectin. This coefficient, together with a simulated geometric mean plasma profile of ivermectin from a published population pharmacokinetic model, was utilized to develop a minimal physiologically-based pharmacokinetic (mPBPK) model. The mPBPK model accurately described the simulated ivermectin plasma concentration profile in humans. The mPBPK model was also used to simulate human lung exposure to ivermectin after 12, 30, and 120 mg oral doses. The simulated ivermectin lung exposures reached a maximum concentration of 772 ng/mL, far less than the estimated 1750 ng/mL IC50 reported for ivermectin against SARS-CoV-2 in vitro. Further studies of ivermectin either reformulated for inhaled delivery or in combination with other antivirals with differing mechanisms of action is needed to assess its therapeutic potential.