Remdesivir-induced emergence of SARS-CoV2 variants in patients with prolonged infection
Andreas Heyer, Thomas Günther, Alexis Robitaille, Marc Lütgehetmann, Marylyn M. Addo, Dominik Jarczak, Stefan Kluge, Martin Aepfelbacher, Julian Schulze zur Wiesch, Nicole Fischer, Adam Grundhoff
Abstract
We here investigate the impact of antiviral treatments such as remdesivir on intra-host genomic diversity and emergence of SARS-CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis performed in 112 longitudinal respiratory samples from 14 SARS-CoV2-infected patients with severe disease progression show that major frequency variants do not generally arise during prolonged infection. However, remdesivir treatment can increase intra-host genomic diversity and result in the emergence of novel major variant species harboring fixed mutations. This is particularly evident in a patient with B cell depletion who rapidly developed mutations in the RNA-dependent RNA polymerase gene following remdesivir treatment. Remdesivir treatment-associated emergence of novel variants is of great interest in light of current treatment guidelines for hospitalized patients suffering from severe SARS-CoV2 disease, as well as the potential use of remdesivir to preventively treat non-hospitalized patients at high risk for severe disease progression.