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: Evolution; SARS-CoV-2; Science; Acclimatization; Q; Spike Glycoprotein, Coronavirus; Humans; COVID-19; Infection; Antibodies, Viral; Antibodies, Neutralizing; Article

AbstractPersistent 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.