ArticleInfection and drug resistance2024
Emergence of SARS-CoV-2 with Dual-Drug Resistant Mutations During a Long-Term Infection in a Kidney Transplant Recipient.
Article in Infection and drug resistance, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- RNA Polymerase Inhibitor Enisamium for Treatment of Moderate COVID-19 Patients: A Randomized, Placebo-Controlled, Multicenter, Double-Blind Phase 3 Clinical Trial.Advances in respiratory medicine · 2024Trial
- Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections.Nature communications · 2026Article
- Corrected and republished from: "Clinical validation of an RSV neutralization assay and analysis of cross-sectional sera associated with 2021-2023 RSV outbreaks to investigate the immunity debt hypothesis".Microbiology spectrum · 2026Article
- SARS-CoV-2 Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug Resistance.Viruses · 2025Article
- A general and biomedical perspective of viral quasispecies.RNA (New York, N.Y.) · 2025Review
- The Emergence of Escape Mutations in COVID-19 Following Anti-Spike Monoclonal Antibody Treatment: How Do We Tackle It?Infection and drug resistance · 2025Review
- Nirmatrelvir Resistance in an Immunocompromised Patient with Persistent Coronavirus Disease 2019.Viruses · 2024Article
- SARS-CoV-2 resistance to monoclonal antibodies and small-molecule drugs.Cell chemical biology · 2024Review
- Enhanced detection and molecular modeling of adaptive mutations in SARS-CoV-2 coding and non-coding regions using the c/µ test.Virus evolution · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Various therapeutic agents are being developed for the treatment of coronavirus disease 2019 (COVID-19). Therefore, it is crucial to accumulate information regarding the features of drug-resistant viruses to these antiviral drugs. Methods: We investigated the emergence of dual-drug resistance in a kidney transplant recipient who received sotrovimab (from day 0) and remdesivir (RDV) (from day 8 to day 17). We sequenced the whole viral genomes from nasopharyngeal swabs taken on day 0 and seven points after starting treatment (on days 12, 19, 23, 37, 43, 48, and 58). The genetic traits of the wild-type (day 0) and descendant viruses (after day 12) were determined by comparing the genomes with those of a Wuhan strain and the day 0 wild-type strain, respectively. Three viral isolates (from samples collected on days 0, 23, and 37) were investigated for their escape ability and growth kinetics in vitro. Results: The sotrovimab resistant mutation (S:E340K) and the RDV resistant mutation RdRp:V792I (nt: G15814A) emerged within 12 days (day 12) and 11 days (day 19) after the treatment, respectively. The day 23 isolate harboring S:E340K/RdRp:V791I was resistant to both sotrovimab and RDV, showing 364- and 2.73-fold higher resistance respectively, compared with the wild-type. Moreover, compared with the day 23 isolate, the day 37 isolate accumulated multiple additional mutations and had a higher level of resistance to both drugs. Conclusion: Drug-resistant variants with double mutations (S:E340K/RdRp:V791I) became dominant within 23 days after starting treatment, suggesting that even a combination therapy involving sotrovimab and RDV, dual-drug resistant viruses may emerge rapidly in immunocompromised patients. The dual-resistant variants had lower virus yields than those of the wild-type virus in vitro, suggesting that they paid a fitness cost.
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