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Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

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, Craig D. Westover, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Phyllis Ruggiero, Bradley W. Langhorst, Nathan Tanner, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Jenny Xiang, Angelika Iftner, Daniela Bezdan, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Iman Hajirasouliha, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Shawn Levy, Melissa Cushing, 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
3The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
4WorldQuant 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
2Tri-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
3The 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
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Ebrahim Afshinnekoo
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
3The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
4WorldQuant 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
7Baylor College of Medicine, Houston, TX, USA
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Nikolay A. Ivanov
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
3The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
8Clinical & 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
13Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Germany
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Michael Zietz
14Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, NY, USA
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Undina Gisladottir
14Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, 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
15New England Biolabs, MA, USA
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Nathan Tanner
15New 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
2Tri-Institutional Computational Biol. & Medicine Program, Weill Cornell Medicine, NY, USA
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Dong Xu
10Genomics Resources Core Facility, Weill Cornell Medicine, NY, USA
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Jenny Xiang
8Clinical & Translational Science Center, Weill Cornell Medicine, NY, USA
10Genomics Resources Core Facility, Weill Cornell Medicine, NY, USA
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Angelika Iftner
13Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Germany
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Daniela Bezdan
13Institute 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
16Department of Medicine, Weill Cornell Medicine, NY, USA
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Iman Hajirasouliha
1Department of Physiology and Biophysics, Weill Cornell Medicine, NY, USA
3The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
17Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, NY, USA
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Thomas Iftner
13Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Germany
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Mirella Salvatore
9Division 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
9Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, NY, USA
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Shawn Levy
11HudsonAlpha Discovery Institute, Huntsville, AL, USA
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Melissa Cushing
6Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, NY, USA
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Nicholas Tatonetti
14Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, NY, USA
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Marcin Imielinski
5New York Genome Center, NY, USA
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
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
3The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, NY, USA
5New York Genome Center, NY, USA
12The 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

A global pandemic of the 2019 coronavirus disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is responsible for over 150,000 deaths worldwide, including >12,000 deaths in New York City (NYC) alone. Given the rapid emergence of this pathogen, little is known about its genetic variation, immune system interactions, population prevalence, and environmental distribution. As a result, there is a pressing clinical and public health need for scalable molecular technologies that can rapidly detect SARS-CoV-2 infection and robustly interrogate strain evolution and host response in patients. To address these challenges, we designed a loop-mediated isothermal amplification (LAMP) assay to identify SARS-CoV-2 infection within 30 minutes of application, including directly from lysed cells. Simultaneously, we developed a large-scale host and viral transcriptomic profiling platform that employs total RNA sequencing (RNA-seq) of nasopharyngeal swab specimens. Applying both technologies to 442 samples, spanning 338 clinical samples tested for SARS-CoV-2, 86 environmental samples from the NYC subway, and 14 controls, we assembled a broad molecular picture of the COVID-19 epidemic in NYC. We found close concordance between viral titers measured with our rapid LAMP assay, RNA-seq, and the state-of-the-art RT-PCR. Full transcriptomic analyses revealed a distinct subset of the Western European clade A2a as the predominant genomic subtype in NYC cases, which was defined by two single nucleotide variants in nsp2 and ORF 3a and a clade-specific, 9-bp in-frame deletion in the virulence factor nsp1. High SARS-CoV2 viral titers were associated with distinct host transcriptional responses, including activation of the ACE2 gene and interferon response genes (e.g., IFIT1). Since ACE inhibitors (ACEIs) can also increase ACE2 expression, outcomes for patients taking ACEIs were examined, and showed a significantly increased risk of intubation and death. Our results demonstrate the utility of two molecular diagnostic platforms in defining the genetic features of an evolving global pandemic and provide insights that can aid future COVID-19 diagnostics, public health monitoring, and therapeutic options.

Competing Interest Statement

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

Footnotes

  • Updated text for clarity.

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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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Posted April 20, 2020.
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Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
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, Craig D. Westover, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Phyllis Ruggiero, Bradley W. Langhorst, Nathan Tanner, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Jenny Xiang, Angelika Iftner, Daniela Bezdan, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Iman Hajirasouliha, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Shawn Levy, Melissa Cushing, 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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Host, Viral, and Environmental Transcriptome Profiles of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
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, Craig D. Westover, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Phyllis Ruggiero, Bradley W. Langhorst, Nathan Tanner, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Jenny Xiang, Angelika Iftner, Daniela Bezdan, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Iman Hajirasouliha, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Shawn Levy, Melissa Cushing, 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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