Potency and timing of antiviral therapy as determinants of duration of SARS CoV-2 shedding and intensity of inflammatory response

Ashish Goyal; E. Fabian Cardozo-Ojeda; Joshua T Schiffer

Using a multi-compartment PK/PD model for hydroxychloroquine (Fig. S3a) , we first recapitulated drug levels of the drug over time following a single dose (Fig. S3b) , simulated twice daily doses over 10 days (Fig. S3c) , generated theoretical dose response curves (Fig. S3d) , and then projected drug efficacy over time (Fig. S3e) . As with remdesivir, the predicted efficacy of therapy on shedding depended on timing of treatment and the intracellular in vivo EC50 (Fig. S4a-e) . Lowering the area under the curve again required extremely early initiation of potent treatment (Fig. S4f) while decreasing the number of effector cells required effective dosing within the first 5 days of infection (Fig. S4g) .