tetano
Editor, Senior Moderator
Nat Commun
. 2024 Sep 18;15(1):7999.
doi: 10.1038/s41467-024-51924-3. Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections
Mohammed Nooruzzaman[SUP] #[/SUP][SUP] 1 [/SUP], Katherine E E Johnson[SUP] #[/SUP][SUP] 2 [/SUP], Ruchi Rani[SUP] 1 [/SUP], Eli J Finkelsztein[SUP] 3 [/SUP], Leonardo C Caserta[SUP] 1 [/SUP], Rosy P Kodiyanplakkal[SUP] 3 [/SUP], Wei Wang[SUP] 2 [/SUP], Jingmei Hsu[SUP] 3 4 [/SUP], Maria T Salpietro[SUP] 5 [/SUP], Stephanie Banakis[SUP] 2 [/SUP], Joshua Albert[SUP] 2 [/SUP], Lars F Westblade[SUP] 6 [/SUP], Claudio Zanettini[SUP] 6 [/SUP], Luigi Marchionni[SUP] 6 [/SUP], Rosemary Soave[SUP] 3 [/SUP], Elodie Ghedin[SUP] 7 [/SUP], Diego G Diel[SUP] 8 [/SUP], Mirella Salvatore[SUP] 9 10 [/SUP]
Affiliations
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 (n = 3) or therapeutic monoclonal antibodies (n = 4). 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 sequentially treated with nirmatrelvir-ritonavir and remdesivir. 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.
. 2024 Sep 18;15(1):7999.
doi: 10.1038/s41467-024-51924-3. Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections
Mohammed Nooruzzaman[SUP] #[/SUP][SUP] 1 [/SUP], Katherine E E Johnson[SUP] #[/SUP][SUP] 2 [/SUP], Ruchi Rani[SUP] 1 [/SUP], Eli J Finkelsztein[SUP] 3 [/SUP], Leonardo C Caserta[SUP] 1 [/SUP], Rosy P Kodiyanplakkal[SUP] 3 [/SUP], Wei Wang[SUP] 2 [/SUP], Jingmei Hsu[SUP] 3 4 [/SUP], Maria T Salpietro[SUP] 5 [/SUP], Stephanie Banakis[SUP] 2 [/SUP], Joshua Albert[SUP] 2 [/SUP], Lars F Westblade[SUP] 6 [/SUP], Claudio Zanettini[SUP] 6 [/SUP], Luigi Marchionni[SUP] 6 [/SUP], Rosemary Soave[SUP] 3 [/SUP], Elodie Ghedin[SUP] 7 [/SUP], Diego G Diel[SUP] 8 [/SUP], Mirella Salvatore[SUP] 9 10 [/SUP]
Affiliations
- PMID: 39294134
- DOI: 10.1038/s41467-024-51924-3
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 (n = 3) or therapeutic monoclonal antibodies (n = 4). 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 sequentially treated with nirmatrelvir-ritonavir and remdesivir. 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.