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

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.

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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Declaration of interests S.K. received research support from Cytosorbents and Daiichi Sankyo. He also received lecture fees from Astra, Bard, Baxter, Biotest, Cytosorbents, Daiichi Sankyo, Fresenius Medical Care, Gilead, Mitsubishi Tanabe Pharma, MSD, Pfizer, Philips, and Zoll. He received consultant fees from Fresenius, Gilead, MSD, and Pfizer. J.S.zW. received consultant and lecture fees from Gilead.