Use of whole genome sequencing to identify low-frequency mutations in SARS-COV-2 patients treated with remdesivir

Remdesivir (RDV) has been shown to reduce hospitalization and mortality in COVID-19 patients. Resistance mutations caused by RDV are rare and when identified have mostly been in patients who are on prolonged therapy and immunocompromised. Resistance can develop when sub-optimal treatment with the drug occurs, and therefore we investigated the effects of short courses of RDV treatment on low-frequency drug resistance mutations in moderately ill hospitalized COVID-19 patients and compared them to patients without RDV treatment. Drug-resistant mutations in nsp12 were not identified during short courses of RDV therapy. We did not detect significant differences in within-host diversity and positive selection between the RDV-treated and untreated groups. Minimal intra-host variability and low-frequency variants were detected in moderately ill patients, which suggests little selective pressure in patients receiving short courses of RDV. The barrier to RDV resistance is high in patients with moderate disease. Ongoing surveillance is needed to ensure that the frequency of mutations in SARS-CoV-2 that confer resistance to RDV remains low.

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