Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants

Ana S. Gonzalez-Reiche, Hala Alshammary, Sarah Schaefer, Gopi Patel, Jose Polanco, Juan Manuel Carreño, Angela A. Amoako, Aria Rooker, Christian Cognigni, Daniel Floda, Adriana Guchte, Zain Khalil, Keith Farrugia, Nima Assad, Jian Zhang, Bremy Alburquerque, Levy A. Sominsky, Charles Gleason, Komal Srivastava, Robert Sebra, Juan David Ramirez, Radhika Banu, Paras Shrestha, Florian Krammer, Alberto Paniz-Mondolfi, Emilia Mia Sordillo (), Viviana Simon () and Harm Bakel ()
Additional contact information
Ana S. Gonzalez-Reiche: Icahn School of Medicine at Mount Sinai
Hala Alshammary: Icahn School of Medicine at Mount Sinai
Sarah Schaefer: Icahn School of Medicine at Mount Sinai
Gopi Patel: Icahn School of Medicine at Mount Sinai
Jose Polanco: Icahn School of Medicine at Mount Sinai
Juan Manuel Carreño: Icahn School of Medicine at Mount Sinai
Angela A. Amoako: Icahn School of Medicine at Mount Sinai
Aria Rooker: Icahn School of Medicine at Mount Sinai
Christian Cognigni: Icahn School of Medicine at Mount Sinai
Daniel Floda: Icahn School of Medicine at Mount Sinai
Adriana Guchte: Icahn School of Medicine at Mount Sinai
Zain Khalil: Icahn School of Medicine at Mount Sinai
Keith Farrugia: Icahn School of Medicine at Mount Sinai
Nima Assad: Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai
Jian Zhang: Icahn School of Medicine at Mount Sinai
Bremy Alburquerque: Icahn School of Medicine at Mount Sinai
Levy A. Sominsky: Icahn School of Medicine at Mount Sinai
Charles Gleason: Icahn School of Medicine at Mount Sinai
Komal Srivastava: Icahn School of Medicine at Mount Sinai
Robert Sebra: Icahn School of Medicine at Mount Sinai
Juan David Ramirez: Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai
Radhika Banu: Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai
Paras Shrestha: Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai
Florian Krammer: Icahn School of Medicine at Mount Sinai
Alberto Paniz-Mondolfi: Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai
Emilia Mia Sordillo: Molecular, and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai
Viviana Simon: Icahn School of Medicine at Mount Sinai
Harm Bakel: Icahn School of Medicine at Mount Sinai

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38867-x

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