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Recent:   

Human SARS-CoV-2 challenge uncovers local and systemic response dynamics

Lindeboom et al., Nature, doi:10.1038/s41586-024-07575-x
Jun 2024  
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Human SARS-CoV-2 challenge experiment, using single-cell multi-omics profiling to analyze nasopharyngeal and blood samples over time. Authors found that ciliated epithelial cells in the nasopharynx were the primary targets for productive SARS-CoV-2 infection, with some becoming "hyperinfected" and serving as major viral producers. While viral RNA was also detected in other cell types such as goblet cells, CD8+ T cells, and macrophages, only epithelial cells showed evidence of supporting successful viral replication.
Lindeboom et al., 19 Jun 2024, peer-reviewed, 44 authors. Contact: r.lindeboom@nki.nl, m.nikolic@ucl.ac.uk, sat1003@cam.ac.uk.
This PaperMiscellaneousAll
Human SARS-CoV-2 challenge uncovers local and systemic response dynamics
Rik G H Lindeboom, Kaylee B Worlock, Lisa M Dratva, Masahiro Yoshida, David Scobie, Helen R Wagstaffe, Laura Richardson, Anna Wilbrey-Clark, Josephine L Barnes, Lorenz Kretschmer, Krzysztof Polanski, Jessica Allen-Hyttinen, Puja Mehta, Dinithi Sumanaweera, Jacqueline M Boccacino, Waradon Sungnak, Rasa Elmentaite, Ni Huang, Lira Mamanova, Rakesh Kapuge, Liam Bolt, Elena Prigmore, Ben Killingley, Mariya Kalinova, Maria Mayer, Alison Boyers, Alex Mann, Leo Swadling, Maximillian N J Woodall, Samuel Ellis, Claire M Smith, Vitor H Teixeira, Sam M Janes, Rachel C Chambers, Muzlifah Haniffa, Andrew Catchpole, Robert Heyderman, Mahdad Noursadeghi, Benny Chain, Andreas Mayer, Kerstin B Meyer, Christopher Chiu, Marko Z Nikolić, Sarah A Teichmann
Nature, doi:10.1038/s41586-024-07575-x
bias as participation was voluntary and instigated by the volunteers. Due to these factors, direct extrapolation of the results to young children, older adults, those with pre-existing conditions and minority groups may not be possible.
Article Sanger Institute through the Sanger Prize. This publication is part of the Human Cell Atlas (https://www.humancellatlas.org/publications). Illustrations in Fig. 1 and Extended Data Fig. 10 were created using BioRender (https://www.biorender.com). For the purpose of Open Access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. Author contributions M.Z.N. and S.A.T. conceived, set up, directed this study and provided funding. C.C. set up the clinical study and co-ordinated sampling. K.B.W. optimized digestion protocols, processed samples for 10x and CITE-seq, isolated DNA for genotyping, performed Dextramer experiments and assisted with data analyses and interpretation. R.G.H.L. performed and led the data analyses. L.M.D. assisted with data analyses and implemented Cell2TCR in Python. L.K., J.M.B., R.E., K.P., W.S., N.H. and D. Sumanaweera advised on and assisted with data analyses. R.G.H.L., K.B.W., L.M.D., K.B.M., M.Z.N. and S.A.T. interpreted the data and wrote the manuscript. L.R., A.W.-C., L.M., R.K., L.B. and E.P. performed the single-cell sequencing library preparations. M.Y., J.L.B. and J.A.-H. assisted with CITE-seq and 10x sample processing. V.H.T., S.M.J. and R.C.C. provided student supervision to K.B.W. and P.M. H.R.W. processed blood samples. D. Scobie, B.C. and A. Mayer provided bulk TCR-seq data and advised on the data analysis. P.M. collected nasopharyngeal samples for..
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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 <jats:italic>HLA-DQA2</jats:italic> ' 'before inoculation was associated with preventing sustained infection. Ciliated cells showed ' 'multiple immune responses and were most permissive for viral replication, whereas ' 'nasopharyngeal T\u2009cells and macrophages were infected non-productively. We resolved 54 ' 'T\u2009cell states, including acutely activated T\u2009cells that clonally expanded while ' 'carrying convergent SARS-CoV-2 motifs. Our new computational pipeline Cell2TCR identifies ' 'activated antigen-responding T\u2009cells based on a gene expression signature and clusters ' 'these into clonotype groups and motifs. 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Physiol.'}], 'container-title': 'Nature', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41586-024-07575-x.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41586-024-07575-x', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41586-024-07575-x.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 6, 19]], 'date-time': '2024-06-19T16:08:02Z', 'timestamp': 1718813282000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41586-024-07575-x'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 6, 19]]}, 'references-count': 63, 'alternative-id': ['7575'], 'URL': 'http://dx.doi.org/10.1038/s41586-024-07575-x', 'relation': {}, 'ISSN': ['0028-0836', '1476-4687'], 'subject': [], 'container-title-short': 'Nature', 'published': {'date-parts': [[2024, 6, 19]]}, 'assertion': [ { 'value': '24 February 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '16 May 2024', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '19 June 2024', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'R.G.H.L., L.M.D., R.E. and S.A.T. are inventors on a filed patent that is ' 'related to the detection and application of activated T\u2009cells. In the past ' '3\u2009years, S.A.T. has received remuneration for scientific advisory board ' 'membership from Sanofi, GlaxoSmithKline, Foresite Labs and Qiagen. S.A.T. is a ' 'co-founder and holds equity in Transition Bio and Ensocell. From 8 January ' '2024, S.A.T. is a part-time employee of GlaxoSmithKline. R.E. is a co-founder ' 'and equity holder in Ensocell. P.M. is a Medical Research Council ' '(MRC)-GlaxoSmithKline EMINENT clinical training fellow with project funding ' 'unrelated to the topic of this work and receives co-funding from the National ' 'Institute for Health Research (NIHR) University College London Hospitals (UCLH) ' 'Biomedical Research Centre. P.M. reports consultancy fees from SOBI, AbbVie, ' 'UCB, Lilly, Boehringer Ingelheim and EUSA Pharma, all unrelated to this study. ' 'S.M.J. has received fees for advisory board membership in the last three years ' 'from Bard1 Lifescience. He has received grant income from GRAIL Inc. He is an ' 'unpaid member of a GRAIL advisory board. He has received lecture fees for ' 'academic meetings from Cheisi and AstraZeneca. His wife works for AstraZeneca. ' 'R.C.C. has research collaborations with Chiesi Chiesi Farmaceutici S.p.A. and ' 'GSK and receives consulting fees from Vicore, outside the submitted work.\xa0' 'A.\xa0Mann, A.C., M.K., M.M. and A.B. are full-time employees at hVIVO ' 'Services. The other authors declare no competing interests.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}]}
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