TY - JOUR
T1 - Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants
AU - Gonzalez-Reiche, Ana S.
AU - Alshammary, Hala
AU - Schaefer, Sarah
AU - Patel, Gopi
AU - Polanco, Jose
AU - Carreño, Juan Manuel
AU - Amoako, Angela A.
AU - Rooker, Aria
AU - Cognigni, Christian
AU - Floda, Daniel
AU - van de Guchte, Adriana
AU - Khalil, Zain
AU - Farrugia, Keith
AU - Assad, Nima
AU - Zhang, Jian
AU - Alburquerque, Bremy
AU - Kleiner, Giulio
AU - Andre, Dalles
AU - Beach, Katherine F.
AU - Bermúdez-González, Maria C.
AU - Cai, Gianna
AU - Lyttle, Neko
AU - Mulder, Lubbertus C.F.
AU - Oostenink, Annika
AU - Salimbangon, Ashley Beathrese T.
AU - Singh, Gagandeep
AU - van Kesteren, Morgan
AU - Monahan, Brian
AU - Mauldin, Jacob
AU - Awawda, Mahmoud
AU - Sominsky, Levy A.
AU - Gleason, Charles
AU - Srivastava, Komal
AU - Sebra, Robert
AU - Ramirez, Juan David
AU - Banu, Radhika
AU - Shrestha, Paras
AU - Krammer, Florian
AU - Paniz-Mondolfi, Alberto
AU - Sordillo, Emilia Mia
AU - Simon, Viviana
AU - van Bakel, Harm
N1 - Funding Information:
We thank the Mount Sinai Hospital and School Leadership, in particular Dr. David Reich, Dr. Dennis Charney, and Dr. Carlos Cordon-Cardo, for their ongoing support of the MS-PSP throughout the pandemic. We thank the laboratory technologists and staff in the Molecular Microbiology Laboratories and the Rapid Response Laboratories of the Mount Sinai Health System since without their assistance and help, none of this surveillance work would be possible. We thank Dr. R. A. Albrecht for oversight of the conventional BSL-3 biocontainment facility at Mount Sinai, which makes our work with replication-competent SARS-CoV-2 isolates possible. We gratefully acknowledge the authors and originating and submitting laboratories of sequences from GISAID’s EpiCoV (www.gisaid.org) that were used as background for our phylogenetic inferences. The work reported was, in part, supported by a contract from the National Institute of Allergy and Infectious Diseases (75N93021C00014, Option 12 A, to V.S. and H.v.B.) awarded to the Center for Research on Influenza Pathogenesis and Transmission and by an Option to the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 (to F.K. and V.S.) as part of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) Program, a contract from the National Institute of Allergy and Infectious Diseases (HHSN272201400008C, Option 20, to V.S., F.K., and H.v.B.) awarded to the Center for Research on Influenza Pathogenesis, and awards (S10OD026880 and S10OD030463, to ISMMS) from the NIH Office of Research Infrastructure Programs. Additional support was provided by R21AI169280 (to V.S.) and U19AI168631 (to V.S., F.K., and H.v.B.). The Mount Sinai Pathogen Surveillance Program is supported in part by Institutional funds from the Icahn School of Medicine as well as the Mount Sinai Hospital (to E.M.S., V.S. and H.v.B.). This work was also supported in part through the computational and data resources and staff expertise provided by Scientific Computing and Data at the Icahn School of Medicine at Mount Sinai and supported by the Clinical and Translational Science Awards (CTSA) grant UL1TR004419 from the National Center for Advancing Translational Sciences (to the Icahn School of Medicine at Mount Sinai).
Funding Information:
We thank the Mount Sinai Hospital and School Leadership, in particular Dr. David Reich, Dr. Dennis Charney, and Dr. Carlos Cordon-Cardo, for their ongoing support of the MS-PSP throughout the pandemic. We thank the laboratory technologists and staff in the Molecular Microbiology Laboratories and the Rapid Response Laboratories of the Mount Sinai Health System since without their assistance and help, none of this surveillance work would be possible. We thank Dr. R. A. Albrecht for oversight of the conventional BSL-3 biocontainment facility at Mount Sinai, which makes our work with replication-competent SARS-CoV-2 isolates possible. We gratefully acknowledge the authors and originating and submitting laboratories of sequences from GISAID’s EpiCoV ( www.gisaid.org ) that were used as background for our phylogenetic inferences. The work reported was, in part, supported by a contract from the National Institute of Allergy and Infectious Diseases (75N93021C00014, Option 12 A, to V.S. and H.v.B.) awarded to the Center for Research on Influenza Pathogenesis and Transmission and by an Option to the Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051 (to F.K. and V.S.) as part of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) Program, a contract from the National Institute of Allergy and Infectious Diseases (HHSN272201400008C, Option 20, to V.S., F.K., and H.v.B.) awarded to the Center for Research on Influenza Pathogenesis, and awards (S10OD026880 and S10OD030463, to ISMMS) from the NIH Office of Research Infrastructure Programs. Additional support was provided by R21AI169280 (to V.S.) and U19AI168631 (to V.S., F.K., and H.v.B.). The Mount Sinai Pathogen Surveillance Program is supported in part by Institutional funds from the Icahn School of Medicine as well as the Mount Sinai Hospital (to E.M.S., V.S. and H.v.B.). This work was also supported in part through the computational and data resources and staff expertise provided by Scientific Computing and Data at the Icahn School of Medicine at Mount Sinai and supported by the Clinical and Translational Science Awards (CTSA) grant UL1TR004419 from the National Center for Advancing Translational Sciences (to the Icahn School of Medicine at Mount Sinai).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85160894508&partnerID=8YFLogxK
U2 - 10.1038/s41467-023-38867-x
DO - 10.1038/s41467-023-38867-x
M3 - Article
C2 - 37270625
AN - SCOPUS:85160894508
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3235
ER -
