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Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions

Daniel Butler, Christopher Mozsary, Cem Meydan, Jonathan Foox, Joel Rosiene, Alon Shaiber, David Danko, Ebrahim Afshinnekoo, Matthew MacKay, Fritz J. Sedlazeck, Nikolay A. Ivanov, Maria Sierra, Diana Pohle, Michael Zietz, Undina Gisladottir, Vijendra Ramlall, Evan T. Sholle, Edward J. Schenck, Craig D. Westover, Ciaran Hassan, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Dianna L. Ng, Andrea C. Granados, Yale A. Santos, Venice Servellita, Scot Federman, Phyllis Ruggiero, Arkarachai Fungtammasan, Chen-Shan Chin, Nathaniel M. Pearson, Bradley W. Langhorst, Nathan A. Tanner, Youngmi Kim, Jason W. Reeves, Tyler D. Hether, Sarah E. Warren, Michael Bailey, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Mara Couto-Rodriguez, Dorottya Nagy-Szakal, Joseph Barrows, Heather Wells, Niamh B. O’Hara, Jeffrey A. Rosenfeld, Ying Chen, Peter A. D. Steel, Amos J. Shemesh, Jenny Xiang, Jean Thierry-Mieg, Danielle Thierry-Mieg, Angelika Iftner, Daniela Bezdan, Elizabeth Sanchez, Thomas R. Campion, John Sipley, Lin Cong, Arryn Craney, Priya Velu, Ari M. Melnick, Sagi Shapira, Iman Hajirasouliha, Alain Borczuk, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Melissa Cushing, Shixiu Wu, Shawn Levy, Charles Chiu, Robert E. Schwartz (), Nicholas Tatonetti (), Hanna Rennert (), Marcin Imielinski () and Christopher E. Mason ()
Additional contact information
Daniel Butler: Weill Cornell Medicine
Christopher Mozsary: Weill Cornell Medicine
Cem Meydan: Weill Cornell Medicine
Jonathan Foox: Weill Cornell Medicine
Joel Rosiene: New York Genome Center
Alon Shaiber: New York Genome Center
David Danko: Weill Cornell Medicine
Ebrahim Afshinnekoo: Weill Cornell Medicine
Matthew MacKay: Weill Cornell Medicine
Fritz J. Sedlazeck: Baylor College of Medicine
Nikolay A. Ivanov: Weill Cornell Medicine
Maria Sierra: Weill Cornell Medicine
Diana Pohle: University Hospital Tuebingen
Michael Zietz: Columbia University
Undina Gisladottir: Columbia University
Vijendra Ramlall: Columbia University
Evan T. Sholle: Weill Cornell Medicine
Edward J. Schenck: Weill Cornell Medicine
Craig D. Westover: Weill Cornell Medicine
Ciaran Hassan: Weill Cornell Medicine
Krista Ryon: Weill Cornell Medicine
Benjamin Young: Weill Cornell Medicine
Chandrima Bhattacharya: Weill Cornell Medicine
Dianna L. Ng: University of California
Andrea C. Granados: University of California
Yale A. Santos: University of California
Venice Servellita: University of California
Scot Federman: University of California
Phyllis Ruggiero: Weill Cornell Medicine
Arkarachai Fungtammasan: DNAnexus, Inc.
Chen-Shan Chin: DNAnexus, Inc.
Nathaniel M. Pearson: Root Deep Insight
Bradley W. Langhorst: New England Biolabs
Nathan A. Tanner: New England Biolabs
Youngmi Kim: NanoString Technologies
Jason W. Reeves: NanoString Technologies
Tyler D. Hether: NanoString Technologies
Sarah E. Warren: NanoString Technologies
Michael Bailey: NanoString Technologies
Justyna Gawrys: Weill Cornell Medicine
Dmitry Meleshko: Weill Cornell Medicine
Dong Xu: Weill Cornell Medicine
Mara Couto-Rodriguez: Biotia, Inc.
Dorottya Nagy-Szakal: Biotia, Inc.
Joseph Barrows: Biotia, Inc.
Heather Wells: Biotia, Inc.
Niamh B. O’Hara: Biotia, Inc.
Jeffrey A. Rosenfeld: Rutgers Cancer Institute of New Jersey
Ying Chen: Rutgers Cancer Institute of New Jersey
Peter A. D. Steel: Weill Cornell Medicine
Amos J. Shemesh: Weill Cornell Medicine
Jenny Xiang: Weill Cornell Medicine
Jean Thierry-Mieg: National Institutes of Health
Danielle Thierry-Mieg: National Institutes of Health
Angelika Iftner: University Hospital Tuebingen
Daniela Bezdan: University Hospital Tuebingen
Elizabeth Sanchez: Weill Cornell Medicine
Thomas R. Campion: Weill Cornell Medicine
John Sipley: Weill Cornell Medicine
Lin Cong: Weill Cornell Medicine
Arryn Craney: Weill Cornell Medicine
Priya Velu: Weill Cornell Medicine
Ari M. Melnick: Weill Cornell Medicine
Sagi Shapira: Columbia University
Iman Hajirasouliha: Weill Cornell Medicine
Alain Borczuk: Weill Cornell Medicine
Thomas Iftner: University Hospital Tuebingen
Mirella Salvatore: Weill Cornell Medicine
Massimo Loda: Weill Cornell Medicine
Lars F. Westblade: Weill Cornell Medicine
Melissa Cushing: Weill Cornell Medicine
Shixiu Wu: Hangzhou Cancer Hospital
Shawn Levy: HudsonAlpha Discovery Institute
Charles Chiu: University of California
Robert E. Schwartz: Weill Cornell Medicine
Nicholas Tatonetti: Columbia University
Hanna Rennert: Weill Cornell Medicine
Marcin Imielinski: New York Genome Center
Christopher E. Mason: Weill Cornell Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) killed over a million people, including >25,000 in New York City (NYC) alone. The COVID-19 pandemic caused by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods to clinical specimens gathered from 669 patients in New York City during the first two months of the outbreak, yielding a broad molecular portrait of the emerging COVID-19 disease. We find significant enrichment of a NYC-distinctive clade of the virus (20C), as well as host responses in interferon, ACE, hematological, and olfaction pathways. In addition, we use 50,821 patient records to find that renin–angiotensin–aldosterone system inhibitors have a protective effect for severe COVID-19 outcomes, unlike similar drugs. Finally, spatial transcriptomic data from COVID-19 patient autopsy tissues reveal distinct ACE2 expression loci, with macrophage and neutrophil infiltration in the lungs. These findings can inform public health and may help develop and drive SARS-CoV-2 diagnostic, prevention, and treatment strategies.

Date: 2021
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DOI: 10.1038/s41467-021-21361-7

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