Prevalence of Low-Frequency, Antiviral Resistance Variants in SARS-CoV-2 Isolates in Ontario, Canada, 2020-2023

Abstract

ImportanceNirmatrelvir-ritonavir is an oral antiviral medication that improves outcomes in SARS-CoV-2 infections. However, there is concern that antiviral resistance will develop and that these viruses could be selected for after treatment.ObjectiveTo determine the prevalence of low-frequency SARS-CoV-2 variants in patient samples that could be selected for by nirmatrelvir-ritonavir.Design, Setting, and ParticipantsThis retrospective cohort study was conducted at 4 laboratories that serve community hospitals, academic tertiary care centers, and COVID-19 assessment centers in Ontario, Canada. Participants included symptomatic or asymptomatic patients who tested positive for SARS-CoV-2 virus and submitted virus samples for diagnostic testing between March 2020 and January 2023.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresSamples with sufficient viral load underwent next-generation genome sequencing to identify low-frequency antiviral resistance variants that could not be identified through conventional sequencing.ResultsThis study included 78 866 clinical samples with next-generation whole-genome sequencing data for SARS-CoV-2. Low-frequency variants in the viral nsp5 gene were identified in 128 isolates (0.16%), and no single variant associated with antiviral resistance was predominate.Conclusions and RelevanceThis cohort study of low-frequency variants resistant to nirmatrelvir-ritonavir found that these variants were very rare in samples from patients with SARS-CoV-2, suggesting that selection of these variants by nirmatrelvir-ritonavir following the initiation of treatment may also be rare. Surveillance efforts that involve sequencing of viral isolates should continue to monitor for novel resistance variants as nirmatrelvir-ritonavir is used more broadly.

Low Prevalence of Nirmatrelvir-Ritonavir Resistance-Associated Mutations in SARS-CoV-2 Lineages From Botswana

“…This may have contributed to the very low prevalence of NTV/r RAMs in Botswana. Although modest, this prevalence is slightly higher compared with 0.5% reported globally and 0.16% reported by a Canadian cohort study [ 32 , 33 ]. The global analysis of NTV/r RAMs by Ip and colleagues [ 33 ] utilized publicly available sequences from GISAID.…”

An expanded RT-PCR melting temperature coding assay to rapidly identify all known SARS-CoV-2 variants and sub-variants of concern

“…The Kraken subvariant (XBB.1.5) could also be distinguishable from other Omicron subvariants since it is WT on the 452 codon but has an additional mutation on 484 codon. The mutations on these codons have been shown to be responsible for the increased infectivity, transmission, escape humoral immunity and reduced susceptibility to monoclonal antibody treatments 13 , 42 , 43 and resistance to antivirals 44 , 45 .…”

Can Nitazoxanide and/or other anti‐viral medications be a solution to long COVID? Case report with a brief literature review

“…1,34,45 Although no viral resistance is detected for Molnupiravir yet, 75 resistance was observed with Remdesivir 34,76,77 and Nirmatrelvir. 34,78,79 Crucially, Nitazoxanide is a host-targeted anti-viral, therefore developing viral resistance is unlikely as compared to RdRp targeting medications such as Remdesivir, Molnupiravir when mutation rates are high on RNA viruses. 80 Moreover, Paxlovid, Remdesivir, and Sotrovimab are not advised to use for below 12 yearolds and Molnupiravir below 18 year-olds nor during pregnancy unlike Nitazoxanide.…”