Human SARS-CoV-2 challenge uncovers local and systemic response dynamics
Issued Date
2024-01-01
Resource Type
ISSN
00280836
eISSN
14764687
Scopus ID
2-s2.0-85196315697
Journal Title
Nature
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature (2024)
Suggested Citation
Lindeboom R.G.H., Worlock K.B., Dratva L.M., Yoshida M., Scobie D., Wagstaffe H.R., Richardson L., Wilbrey-Clark A., Barnes J.L., Kretschmer L., Polanski K., Allen-Hyttinen J., Mehta P., Sumanaweera D., Boccacino J.M., Sungnak W., Elmentaite R., Huang N., Mamanova L., Kapuge R., Bolt L., Prigmore E., Killingley B., Kalinova M., Mayer M., Boyers A., Mann A., Swadling L., Woodall M.N.J., Ellis S., Smith C.M., Teixeira V.H., Janes S.M., Chambers R.C., Haniffa M., Catchpole A., Heyderman R., Noursadeghi M., Chain B., Mayer A., Meyer K.B., Chiu C., Nikolić M.Z., Teichmann S.A. Human SARS-CoV-2 challenge uncovers local and systemic response dynamics. Nature (2024). doi:10.1038/s41586-024-07575-x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98990
Title
Human SARS-CoV-2 challenge uncovers local and systemic response dynamics
Author(s)
Lindeboom R.G.H.
Worlock K.B.
Dratva L.M.
Yoshida M.
Scobie D.
Wagstaffe H.R.
Richardson L.
Wilbrey-Clark A.
Barnes J.L.
Kretschmer L.
Polanski K.
Allen-Hyttinen J.
Mehta P.
Sumanaweera D.
Boccacino J.M.
Sungnak W.
Elmentaite R.
Huang N.
Mamanova L.
Kapuge R.
Bolt L.
Prigmore E.
Killingley B.
Kalinova M.
Mayer M.
Boyers A.
Mann A.
Swadling L.
Woodall M.N.J.
Ellis S.
Smith C.M.
Teixeira V.H.
Janes S.M.
Chambers R.C.
Haniffa M.
Catchpole A.
Heyderman R.
Noursadeghi M.
Chain B.
Mayer A.
Meyer K.B.
Chiu C.
Nikolić M.Z.
Teichmann S.A.
Worlock K.B.
Dratva L.M.
Yoshida M.
Scobie D.
Wagstaffe H.R.
Richardson L.
Wilbrey-Clark A.
Barnes J.L.
Kretschmer L.
Polanski K.
Allen-Hyttinen J.
Mehta P.
Sumanaweera D.
Boccacino J.M.
Sungnak W.
Elmentaite R.
Huang N.
Mamanova L.
Kapuge R.
Bolt L.
Prigmore E.
Killingley B.
Kalinova M.
Mayer M.
Boyers A.
Mann A.
Swadling L.
Woodall M.N.J.
Ellis S.
Smith C.M.
Teixeira V.H.
Janes S.M.
Chambers R.C.
Haniffa M.
Catchpole A.
Heyderman R.
Noursadeghi M.
Chain B.
Mayer A.
Meyer K.B.
Chiu C.
Nikolić M.Z.
Teichmann S.A.
Author's Affiliation
hVIVO Services Limited
UCL Division of Medicine
Department of Physics
University of Cambridge
University College London Hospitals NHS Foundation Trust
University College London
The Netherlands Cancer Institute
Imperial College London
Mahidol University
UCL Great Ormond Street Institute of Child Health
Wellcome Sanger Institute
Biodata Innovation Centre
UCL Division of Medicine
Department of Physics
University of Cambridge
University College London Hospitals NHS Foundation Trust
University College London
The Netherlands Cancer Institute
Imperial College London
Mahidol University
UCL Great Ormond Street Institute of Child Health
Wellcome Sanger Institute
Biodata Innovation Centre
Corresponding Author(s)
Other Contributor(s)
Abstract
The COVID-19 pandemic is an ongoing global health threat, yet our understanding of the dynamics of early cellular responses to this disease remains limited1. Here in our SARS-CoV-2 human challenge study, we used single-cell multi-omics profiling of nasopharyngeal swabs and blood to temporally resolve abortive, transient and sustained infections in seronegative individuals challenged with pre-Alpha SARS-CoV-2. Our analyses revealed rapid changes in cell-type proportions and dozens of highly dynamic cellular response states in epithelial and immune cells associated with specific time points and infection status. We observed that the interferon response in blood preceded the nasopharyngeal response. Moreover, nasopharyngeal immune infiltration occurred early in samples from individuals with only transient infection and later in samples from individuals with sustained infection. High expression of HLA-DQA2 before inoculation was associated with preventing sustained infection. Ciliated cells showed multiple immune responses and were most permissive for viral replication, whereas nasopharyngeal T cells and macrophages were infected non-productively. We resolved 54 T cell states, including acutely activated T cells that clonally expanded while carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies activated antigen-responding T cells based on a gene expression signature and clusters these into clonotype groups and motifs. Overall, our detailed time series data can serve as a Rosetta stone for epithelial and immune cell responses and reveals early dynamic responses associated with protection against infection.