Remdesivir-induced emergence of SARS-CoV2 variants in patients with prolonged infection

We sought to elucidate the influence of antiviral treatments such as remdesivir on intra-host genomic diversity and the emergence of SARS CoV2 variants in patients with a prolonged course of infection. Sequencing and variant analysis were performed in 112 longitudinal respiratory samples from SARSCoV2 infected patients with severe disease course and prolonged virus persistence. We find that fixed mutations did not generally arise in prolonged infections. However, remdesivir treatment increased intra-host genomic diversity and the emergence of major variants harboring fixed mutations. This was particularly evident in a patient with B-cell depletion, who rapidly developed mutations in the RNA-dependent RNA polymerase gene upon remdesivir treatment. Remdesivir-induced genomic diversity and fixation of new mutations are of great interest given the current recommendations in treatment guidelines for the use of remdesivir to treat severe SARS-CoV2 disease and with regard to its potential use in non-hospitalized patients with a high risk for disease progression.