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

Calvin P Sjaarda1,2, Lynette Lau3, Jared T Simpson4,5

  • 1Division of Microbiology, Kingston Health Sciences Centre, Kingston, Ontario, Canada.

JAMA Network Open
|July 21, 2023
PubMed
Abstract

Insights

Low-frequency SARS-CoV-2 variants resistant to nirmatrelvir-ritonavir are rare in patients. This suggests that antiviral resistance selection by nirmatrelvir-ritonavir treatment may also be uncommon, but continued surveillance is recommended.

Area of Science:

  • Virology
  • Infectious Diseases
  • Genomics

Background:

  • Nirmatrelvir-ritonavir is an oral antiviral for SARS-CoV-2 infections.
  • Concerns exist regarding the potential for antiviral resistance development and selection post-treatment.

Purpose of the Study:

  • To determine the prevalence of low-frequency SARS-CoV-2 variants resistant to nirmatrelvir-ritonavir.
  • To assess the potential for these variants to be selected during treatment.

Main Methods:

  • Retrospective cohort study of 78,866 SARS-CoV-2 positive patient samples from Ontario, Canada (March 2020 - January 2023).
  • Next-generation genome sequencing used to identify low-frequency antiviral resistance variants.

Main Results:

  • Low-frequency variants in the viral nsp5 gene were identified in 0.16% (128/78,866) of isolates.
  • No single variant associated with antiviral resistance predominated.

Conclusions:

  • Low-frequency nirmatrelvir-ritonavir-resistant SARS-CoV-2 variants are rare.
  • Selection of these variants by nirmatrelvir-ritonavir treatment is likely uncommon.
  • Continued surveillance for novel resistance variants is crucial as nirmatrelvir-ritonavir use expands.

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