Incomplete antiviral treatment may induce longer durations of viral shedding during SARS-CoV-2 infection

Life Sci Alliance. 2021 Aug 3;4(10):e202101049. doi: 10.26508/lsa.202101049. Print 2021 Oct.

Abstract

The duration of viral shedding is determined by a balance between de novo infection and removal of infected cells. That is, if infection is completely blocked with antiviral drugs (100% inhibition), the duration of viral shedding is minimal and is determined by the length of virus production. However, some mathematical models predict that if infected individuals are treated with antiviral drugs with efficacy below 100%, viral shedding may last longer than without treatment because further de novo infections are driven by entry of the virus into partially protected, uninfected cells at a slower rate. Using a simple mathematical model, we quantified SARS-CoV-2 infection dynamics in non-human primates and characterized the kinetics of viral shedding. We counterintuitively found that treatments initiated early, such as 0.5 d after virus inoculation, with intermediate to relatively high efficacy (30-70% inhibition of virus replication) yield a prolonged duration of viral shedding (by about 6.0 d) compared with no treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / pharmacology
  • Alanine / analogs & derivatives
  • Alanine / pharmacology
  • Animals
  • Antiviral Agents / pharmacology*
  • COVID-19 / virology*
  • COVID-19 Drug Treatment*
  • Lung / virology
  • Macaca mulatta
  • Models, Theoretical
  • Nose / virology
  • Pharynx / virology
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / physiology
  • Time Factors
  • Viral Load / drug effects
  • Virus Replication / drug effects
  • Virus Shedding / drug effects*

Substances

  • Antiviral Agents
  • remdesivir
  • Adenosine Monophosphate
  • Alanine