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.

Details

Title
Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants
Author
Gonzalez-Reiche, Ana S. 1   VIAFID ORCID Logo  ; Alshammary, Hala 2 ; Schaefer, Sarah 3 ; Patel, Gopi 3 ; Polanco, Jose 2 ; Carreño, Juan Manuel 2 ; Amoako, Angela A. 2 ; Rooker, Aria 2 ; Cognigni, Christian 2 ; Floda, Daniel 1 ; van de Guchte, Adriana 1   VIAFID ORCID Logo  ; Khalil, Zain 1 ; Farrugia, Keith 1 ; Assad, Nima 4 ; Zhang, Jian 1 ; Alburquerque, Bremy 5   VIAFID ORCID Logo  ; Kleiner, Giulio 6 ; Andre, Dalles 6 ; Beach, Katherine F. 6 ; Bermúdez-González, Maria C. 6 ; Cai, Gianna 6 ; Lyttle, Neko 6 ; Mulder, Lubbertus C. F. 6 ; Oostenink, Annika 6 ; Salimbangon, Ashley Beathrese T. 6 ; Singh, Gagandeep 6 ; van Kesteren, Morgan 6 ; Monahan, Brian 6 ; Mauldin, Jacob 6 ; Awawda, Mahmoud 7 ; Sominsky, Levy A. 2   VIAFID ORCID Logo  ; Gleason, Charles 2 ; Srivastava, Komal 2 ; Sebra, Robert 8   VIAFID ORCID Logo  ; Ramirez, Juan David 9 ; Banu, Radhika 10 ; Shrestha, Paras 10 ; Krammer, Florian 11   VIAFID ORCID Logo  ; Paniz-Mondolfi, Alberto 10   VIAFID ORCID Logo  ; Sordillo, Emilia Mia 10   VIAFID ORCID Logo  ; Simon, Viviana 12   VIAFID ORCID Logo  ; van Bakel, Harm 13   VIAFID ORCID Logo 

 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 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) 
 Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
 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) 
 Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
 Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, USA (GRID:grid.59734.3c) (ISNI:0000 0001 0670 2351) 
 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) 
 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) 
Pages
3235
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2822004375
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.