TitleShotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions.
Publication TypeJournal Article
Year of Publication2020
AuthorsButler, Daniel J., Mozsary Christopher, Meydan Cem, Danko David, Foox Jonathan, Rosiene Joel, Shaiber Alon, Afshinnekoo Ebrahim, MacKay Matthew, Sedlazeck Fritz J., Ivanov Nikolay A., Sierra Maria, Pohle Diana, Zietz Michael, Gisladottir Undina, Ramlall Vijendra, Westover Craig D., Ryon Krista, Young Benjamin, Bhattacharya Chandrima, Ruggiero Phyllis, Langhorst Bradley W., Tanner Nathan, Gawrys Justyna, Meleshko Dmitry, Xu Dong, Steel Peter A. D., Shemesh Amos J., Xiang Jenny, Thierry-Mieg Jean, Thierry-Mieg Danielle, Schwartz Robert E., Iftner Angelika, Bezdan Daniela, Sipley John, Cong Lin, Craney Arryn, Velu Priya, Melnick Ari M., Hajirasouliha Iman, Horner Stacy M., Iftner Thomas, Salvatore Mirella, Loda Massimo, Westblade Lars F., Cushing Melissa, Levy Shawn, Wu Shixiu, Tatonetti Nicholas, Imielinski Marcin, Rennert Hanna, and Mason Christopher E.
Date Published2020 May 01

<p>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.</p>

Alternate JournalbioRxiv
PubMed ID32511352
PubMed Central IDPMC7255793
Grant ListR01 MH117406 / MH / NIMH NIH HHS / United States
T15 LM007079 / LM / NLM NIH HHS / United States
TL1 TR002386 / TR / NCATS NIH HHS / United States
U19 AI144297 / AI / NIAID NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
R35 GM131905 / GM / NIGMS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
R25 EB020393 / EB / NIBIB NIH HHS / United States
R01 AI151059 / AI / NIAID NIH HHS / United States