2. Academic Validation
  3. Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections

Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections

  • medRxiv. 2024 Jun 18:2024.06.14.24308523. doi: 10.1101/2024.06.14.24308523.
Mohammed Nooruzzaman 1,  Katherine E E Johnson 2,  Ruchi Rani 1,  Eli J Finkelsztein 3,  Leonardo C Caserta 1,  Rosy P Kodiyanplakkal 3,  Wei Wang 2,  Jingmei Hsu 3,  Maria T Salpietro 4,  Stephanie Banakis 2,  Joshua Albert 2,  Lars Westblade 5,  Claudio Zanettini 5,  Luigi Marchionni 5,  Rosemary Soave 3,  Elodie Ghedin 2,  Diego G Diel 1,  Mirella Salvatore 3 6
Affiliations

Affiliations

  • 1 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University.
  • 2 Systems Genomics Section, NIH/NIAID/DIR/LPD.
  • 3 Department of Medicine, Weill Cornell Medicine.
  • 4 Institutional Biorepository Core, Weill Cornell Medicine.
  • 5 Department of Pathology and Laboratory Medicine, Weill Cornell Medicine.
  • 6 Department of Population Health Science, Weill Cornell Medicine.
PMID: 38946967 DOI: 10.1101/2024.06.14.24308523
Abstract

We investigated the impact of Antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n=15). All patients received remdesivir and some also received nirmatrelvir-ritonavir or monoclonal Antibodies. Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C Protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient treated with remdesivir and nirmatrelvir-ritonavir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined Antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact Animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

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