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

• DOI: 10.1038/s41467-023-38867-x
• Publication Date: 2023-06-03T14:01:44Z
• Authors: Ana S. Gonzalez-R...; Hala Alshammary; Sarah Schaefer; Gopi Patel; Jose Polanco; Juan Manuel Carreño; Angela A. Amoako; Aria Rooker; Christian Cognigni; Daniel Floda; Adriana van de Gu...; Zain Khalil; Keith Farrugia; Nima Assad; Jian Zhang; Bremy Alburquerque; ; Giulio Kleiner; Dalles Andre; Katherine F. Beach; Maria C. Bermúdez...; Gianna Cai; Neko Lyttle; Lubbertus C. F. M...; Annika Oostenink; Ashley Beathrese ...; Gagandeep Singh; Morgan van Kesteren; Brian Monahan; Jacob Mauldin; Mahmoud Awawda; Levy A. Sominsky; Charles Gleason; Komal Srivastava; Robert Sebra; Juan David Ramirez; Radhika Banu; Paras Shrestha; Florian Krammer; Alberto Paniz-Mon...; Emilia Mia Sordillo; Viviana Simon; Harm van Bakel
• Keywords: Lineage (genetic); Viral evolution

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 documented, direct evidence of subsequent transmission continued stepwise adaptation is lacking. Here we describe sequential persistent SARS-CoV-2 three that led to the emergence, forward transmission, 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 spike protein (E96D, R346T, L455W, K458M, A484V, H681R, A688V), displayed substantial resistance neutralization by sera from boosted and/or BA.1-infected study participants. Subsequent replication resulted (S254F, N448S, F456L, M458K, F981L, S982L) as well five other virus proteins. Our findings demonstrate not only BA.1 lineage can diverge further its already exceptionally mutated genome but also patients with transmit these viral variants. Thus, there is, urgent need implement strategies prevent prolonged limit spread newly emerging, neutralization-resistant variants vulnerable patients.