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Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium

Jessica K. Fiege, Joshua M. Thiede, Hezkiel Nanda, William E. Matchett, Patrick J. Moore, Noe Rico Montanari, Beth K. Thielen, Jerry Daniel, Emma Stanley, Ryan C. Hunter, Vineet D. Menachery, Steven S. Shen, Tyler D. Bold, Ryan A. Langlois
doi: https://doi.org/10.1101/2020.10.19.343954
Jessica K. Fiege
1Center for Immunology, University of Minnesota
2Department of Microbiology and Immunology, University of Minnesota
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Joshua M. Thiede
3Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota
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Hezkiel Nanda
4Institute for Health Informatics, University of Minnesota
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William E. Matchett
1Center for Immunology, University of Minnesota
2Department of Microbiology and Immunology, University of Minnesota
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Patrick J. Moore
2Department of Microbiology and Immunology, University of Minnesota
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Noe Rico Montanari
2Department of Microbiology and Immunology, University of Minnesota
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Beth K. Thielen
5Department of Pediatrics, Division of Infectious Diseases, University of Minnesota
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Jerry Daniel
6University of Minnesota Genomics Center
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Emma Stanley
6University of Minnesota Genomics Center
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Ryan C. Hunter
1Center for Immunology, University of Minnesota
2Department of Microbiology and Immunology, University of Minnesota
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Vineet D. Menachery
7Department of Microbiology and Immunology, University of Texas Medical Branch
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Steven S. Shen
4Institute for Health Informatics, University of Minnesota
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  • For correspondence: langlois@umn.edu tbold@umn.edu shens@umn.edu
Tyler D. Bold
1Center for Immunology, University of Minnesota
3Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota
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  • For correspondence: langlois@umn.edu tbold@umn.edu shens@umn.edu
Ryan A. Langlois
1Center for Immunology, University of Minnesota
2Department of Microbiology and Immunology, University of Minnesota
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  • For correspondence: langlois@umn.edu tbold@umn.edu shens@umn.edu
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Abstract

The human airway epithelium is the initial site of SARS-CoV-2 infection. We used flow cytometry and single cell RNA-sequencing to understand how the heterogeneity of this diverse cell population contributes to elements of viral tropism and pathogenesis, antiviral immunity, and treatment response to remdesivir. We found that, while a variety of epithelial cell types are susceptible to infection, ciliated cells are the predominant cell target of SARS-CoV-2. The host protease TMPRSS2 was required for infection of these cells. Importantly, remdesivir treatment effectively inhibited viral replication across cell types, and blunted hyperinflammatory responses. Induction of interferon responses within infected cells was rare and there was significant heterogeneity in the antiviral gene signatures, varying with the burden of infection in each cell. We also found that heavily infected secretory cells expressed abundant IL-6, a potential mediator of COVID-19 pathogenesis.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 19, 2020.
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Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium
Jessica K. Fiege, Joshua M. Thiede, Hezkiel Nanda, William E. Matchett, Patrick J. Moore, Noe Rico Montanari, Beth K. Thielen, Jerry Daniel, Emma Stanley, Ryan C. Hunter, Vineet D. Menachery, Steven S. Shen, Tyler D. Bold, Ryan A. Langlois
bioRxiv 2020.10.19.343954; doi: https://doi.org/10.1101/2020.10.19.343954
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Single cell resolution of SARS-CoV-2 tropism, antiviral responses, and susceptibility to therapies in primary human airway epithelium
Jessica K. Fiege, Joshua M. Thiede, Hezkiel Nanda, William E. Matchett, Patrick J. Moore, Noe Rico Montanari, Beth K. Thielen, Jerry Daniel, Emma Stanley, Ryan C. Hunter, Vineet D. Menachery, Steven S. Shen, Tyler D. Bold, Ryan A. Langlois
bioRxiv 2020.10.19.343954; doi: https://doi.org/10.1101/2020.10.19.343954

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