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Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions

Daniel J. Butler, Christopher Mozsary, Cem Meydan, David Danko, Jonathan Foox, Joel Rosiene, Alon Shaiber, Ebrahim Afshinnekoo, Matthew MacKay, Fritz J. Sedlazeck, Nikolay A. Ivanov, Maria Sierra, Diana Pohle, Michael Zietz, Undina Gisladottir, Vijendra Ramlall, Craig D. Westover, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Phyllis Ruggiero, Bradley W. Langhorst, Nathan Tanner, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Peter A. D. Steel, Amos J. Shemesh, Jenny Xiang, Jean Thierry-Mieg, Danielle Thierry-Mieg, Robert E. Schwartz, Angelika Iftner, Daniela Bezdan, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Iman Hajirasouliha, Stacy M. Horner, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Melissa Cushing, Shawn Levy, Shixiu Wu, View ORCID ProfileNicholas Tatonetti, Marcin Imielinski, Hanna Rennert, View ORCID ProfileChristopher E. Mason
doi: https://doi.org/10.1101/2020.04.20.048066
Daniel J. Butler
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Christopher Mozsary
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Cem Meydan
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
2The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
3WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, NY, USA
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David Danko
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
4Tri-Institutional Computational Biol. & Medicine Program, Weill Cornell Medicine, NY, USA
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Jonathan Foox
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
2The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
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Joel Rosiene
5New York Genome Center, NY, USA
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Alon Shaiber
5New York Genome Center, NY, USA
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
7Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, NY, USA
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Ebrahim Afshinnekoo
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
2The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
3WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, NY, USA
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Matthew MacKay
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Fritz J. Sedlazeck
8Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
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Nikolay A. Ivanov
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
2The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
9Clinical & Translational Science Center, Weill Cornell Medicine, NY, USA
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Maria Sierra
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Diana Pohle
10Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Germany
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Michael Zietz
11Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, NY, USA
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Undina Gisladottir
11Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, NY, USA
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Vijendra Ramlall
11Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, NY, USA
12Department of Cellular, Molecular Physiology & Biophysics, Columbia University, NY, USA
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Craig D. Westover
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Krista Ryon
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Benjamin Young
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Chandrima Bhattacharya
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
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Phyllis Ruggiero
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Bradley W. Langhorst
13New England Biolabs, MA, USA
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Nathan Tanner
13New England Biolabs, MA, USA
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Justyna Gawrys
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Dmitry Meleshko
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
4Tri-Institutional Computational Biol. & Medicine Program, Weill Cornell Medicine, NY, USA
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Dong Xu
14Genomics Resources Core Facility, Weill Cornell Medicine, NY, USA
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Peter A. D. Steel
15Department of Emergency Medicine, Weill Cornell Medicine, NY, USA
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Amos J. Shemesh
15Department of Emergency Medicine, Weill Cornell Medicine, NY, USA
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Jenny Xiang
14Genomics Resources Core Facility, Weill Cornell Medicine, NY, USA
16Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, NY, USA
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Jean Thierry-Mieg
17National Center for Biotechnology Information, National Library of Medicine, National Institute of Health, MD, USA
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Danielle Thierry-Mieg
17National Center for Biotechnology Information, National Library of Medicine, National Institute of Health, MD, USA
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Robert E. Schwartz
18Department of Medicine, Weill Cornell Medicine, NY, USA
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Angelika Iftner
10Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Germany
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Daniela Bezdan
10Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Germany
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John Sipley
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Lin Cong
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Arryn Craney
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Priya Velu
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Ari M. Melnick
18Department of Medicine, Weill Cornell Medicine, NY, USA
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Iman Hajirasouliha
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
2The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
7Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, NY, USA
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Stacy M. Horner
19Department of Molecular Genetics and Microbiology, Duke University Medical Center, NC, USA
20Department of Medicine, Duke University Medical Center, NC, USA
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Thomas Iftner
10Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Germany
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Mirella Salvatore
16Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, NY, USA
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Massimo Loda
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Lars F. Westblade
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
16Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, NY, USA
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Melissa Cushing
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Shawn Levy
21HudsonAlpha Discovery Institute, Huntsville, AL, USA
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Shixiu Wu
22Hangzhou Cancer Institute, Hangzhou Cancer Hospital, Hangzhou, China
23Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, China
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Nicholas Tatonetti
11Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, NY, USA
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  • ORCID record for Nicholas Tatonetti
Marcin Imielinski
5New York Genome Center, NY, USA
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
7Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, NY, USA
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  • For correspondence: mai9037@med.cornell.edu har2006@med.cornell.edu chm2042@med.cornell.edu
Hanna Rennert
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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  • For correspondence: mai9037@med.cornell.edu har2006@med.cornell.edu chm2042@med.cornell.edu
Christopher E. Mason
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
2The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
3WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, NY, USA
24The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, NY, USA
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  • ORCID record for Christopher E. Mason
  • For correspondence: mai9037@med.cornell.edu har2006@med.cornell.edu chm2042@med.cornell.edu
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Abstract

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.

Competing Interest Statement

N.T. and B.L. are employees at New England Biolabs.

Footnotes

  • Fixed a typo in the abstract.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions
Daniel J. Butler, Christopher Mozsary, Cem Meydan, David Danko, Jonathan Foox, Joel Rosiene, Alon Shaiber, Ebrahim Afshinnekoo, Matthew MacKay, Fritz J. Sedlazeck, Nikolay A. Ivanov, Maria Sierra, Diana Pohle, Michael Zietz, Undina Gisladottir, Vijendra Ramlall, Craig D. Westover, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Phyllis Ruggiero, Bradley W. Langhorst, Nathan Tanner, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Peter A. D. Steel, Amos J. Shemesh, Jenny Xiang, Jean Thierry-Mieg, Danielle Thierry-Mieg, Robert E. Schwartz, Angelika Iftner, Daniela Bezdan, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Iman Hajirasouliha, Stacy M. Horner, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Melissa Cushing, Shawn Levy, Shixiu Wu, Nicholas Tatonetti, Marcin Imielinski, Hanna Rennert, Christopher E. Mason
bioRxiv 2020.04.20.048066; doi: https://doi.org/10.1101/2020.04.20.048066
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Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions
Daniel J. Butler, Christopher Mozsary, Cem Meydan, David Danko, Jonathan Foox, Joel Rosiene, Alon Shaiber, Ebrahim Afshinnekoo, Matthew MacKay, Fritz J. Sedlazeck, Nikolay A. Ivanov, Maria Sierra, Diana Pohle, Michael Zietz, Undina Gisladottir, Vijendra Ramlall, Craig D. Westover, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Phyllis Ruggiero, Bradley W. Langhorst, Nathan Tanner, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Peter A. D. Steel, Amos J. Shemesh, Jenny Xiang, Jean Thierry-Mieg, Danielle Thierry-Mieg, Robert E. Schwartz, Angelika Iftner, Daniela Bezdan, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Iman Hajirasouliha, Stacy M. Horner, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Melissa Cushing, Shawn Levy, Shixiu Wu, Nicholas Tatonetti, Marcin Imielinski, Hanna Rennert, Christopher E. Mason
bioRxiv 2020.04.20.048066; doi: https://doi.org/10.1101/2020.04.20.048066

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