It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported in immune-compromised individuals and people undergoing immune-modulatory treatments. Although intrahost evolution has been documented, direct evidence of subsequent transmission and continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 infections in three individuals that led to the emergence, forward transmission, and continued evolution of a new Omicron sublineage, BA.1.23, over an eight-month period. The initially transmitted BA.1.23 variant encoded seven additional amino acid substitutions within the spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), and displayed substantial resistance to neutralization by sera from boosted and/or Omicron BA.1-infected study participants. Subsequent continued BA.1.23 replication resulted in additional substitutions in the spike protein (S254F, N448S, F456L, M458K, F981L, S982L) as well as in five other virus proteins. Our findings demonstrate not only that the Omicron BA.1 lineage can diverge further from its already exceptionally mutated genome but also that patients with persistent infections can transmit these viral variants. Thus, there is, an urgent need to implement strategies to prevent prolonged SARS-CoV-2 replication and to limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.
There is limited understanding of SARS-CoV-2 intra-host evolution and subsequent transmission and adaptations in the context of persistent infection. Here, the authors describe sequential persistent SARS-CoV-2 infections that led to the emergence, transmission and further evolution of a novel Omicron BA.1.23 lineage.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details










1 Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
2 Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn School of Medicine at Mount Sinai, Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
3 Icahn School of Medicine at Mount Sinai, Division of Infectious Diseases, Department of Medicine, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
4 Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
5 Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
6 Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
7 Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
8 Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
9 Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Department of Pathology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Centro de Investigaciones en Microbiología y Biotecnología-UR (CIMBIUR), Facultad de Ciencias Naturales, Universidad del Rosario, Bogotá, Colombia (GRID:grid.412191.e) (ISNI:0000 0001 2205 5940)
10 Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Department of Pathology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
11 Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn School of Medicine at Mount Sinai, Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Department of Pathology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
12 Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn School of Medicine at Mount Sinai, Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn School of Medicine at Mount Sinai, Division of Infectious Diseases, Department of Medicine, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, Department of Pathology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); The Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)
13 Icahn School of Medicine at Mount Sinai, Department of Genetics and Genomic Sciences, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351); Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351)