Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions
By
Daniel J Butler,
Christopher Mozsary,
Cem Meydan,
David C 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 E. Levy,
Shixiu Wu,
Nicholas P Tatonetti,
Marcin Imielinski,
Hanna Rennert,
Christopher E Mason
Posted 20 Apr 2020
bioRxiv DOI: 10.1101/2020.04.20.048066
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 ACE, interferon, 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 monitoring, and new therapeutic targets. ### Competing Interest Statement N.T. and B.L. are employees at New England Biolabs.
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