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

SARS CoV-2 infection is characterized by a stereotypical viral kinetic pattern with a high peak viral load during the first several days of infection, a subsequent short rapid decay period followed by a slower clearance phase of variable duration, and a final, rapid elimination phase. Our mathematical model reproduces this data and explains that the transition from first to second phase viral decay is governed by a density dependent term in which a massive die off of infected cells occurs during peak viremia. Viral clearance rate slows considerably once the viral load decreases below a threshold of ~10 5 RNA copies. A late slowly expanding cytolytic T cell response is predicted to induce eradication of infected cells in the upper airway 2-20 days later. The timing of this final response appears to be variable among infected people. Moreover, it is unknown if cessation of viral replication in the nasopharynx guarantees the same result in the lung or other anatomic compartments (8) .