Title | Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Nooruzzaman M, Johnson KEE, Rani R, Finkelsztein EJ, Caserta LC, Kodiyanplakkal RP, Wang W, Hsu JM, Salpietro MT, Banakis S, Albert J, Westblade L, Zanettini C, Marchionni L, Soave R, Ghedin E, Diel DG, Salvatore M |
Journal | medRxiv |
Date Published | 2024 Jun 18 |
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. |
DOI | 10.1101/2024.06.14.24308523 |
Alternate Journal | medRxiv |
PubMed ID | 38946967 |
PubMed Central ID | PMC11213110 |
Grant List | R01 AI166791 / AI / NIAID NIH HHS / United States UL1 TR002384 / TR / NCATS NIH HHS / United States |
Related Faculty:
Luigi Marchionni, M.D., Ph.D. Lars Westblade, Ph.D.