{Reference Type}: Journal Article
{Title}: Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro.
{Author}: Nair MS;Luck MI;Huang Y;Sabo Y;Ho DD;
{Journal}: J Infect Dis
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 12
{Factor}: 7.759
{DOI}: 10.1093/infdis/jiae385
{Abstract}: Reports have described SARS-CoV-2 rebound in COVID-19 patients treated with nirmatrelvir, a 3CL protease inhibitor. The cause remains a mystery, although drug resistance, re-infection, and lack of adequate immune responses have been excluded. We now present virologic findings that provide a clue to the cause of viral rebound, which occurs in ∼20% of the treated cases. Persistence of infectious SARS-CoV-2 was experimentally documented in vitro after treatment with nirmatrelvir or another 3CL protease inhibitor, but not with a polymerase inhibitor, remdesivir. This infectious form decayed slowly with a half-life of ∼1 day, suggesting that its persistence could outlive the treatment course to re-ignite SARS-CoV-2 infection as the drug is eliminated. Notably, extending nirmatrelvir treatment beyond 8 days abolished viral rebound in vitro. Our findings point in a particular direction for future investigation of virus persistence and offer a specific treatment recommendation that should be tested clinically.