Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.
IF: 17.694
Cited by: 53


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.


Spatial Transcriptomics

MeSH terms

Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Antiviral Agents
COVID-19 Nucleic Acid Testing
Drug Interactions
Gene Expression Profiling
Genome, Viral
HLA Antigens
Host Microbial Interactions
Middle Aged
Molecular Diagnostic Techniques
New York City
Nucleic Acid Amplification Techniques


Butler, Daniel
Mozsary, Christopher
Meydan, Cem
Foox, Jonathan
Rosiene, Joel
Shaiber, Alon
Danko, David
Afshinnekoo, Ebrahim
MacKay, Matthew
Sedlazeck, Fritz J
Ivanov, Nikolay A
Sierra, Maria
Pohle, Diana
Zietz, Michael
Gisladottir, Undina
Ramlall, Vijendra
Sholle, Evan T
Schenck, Edward J
Westover, Craig D
Hassan, Ciaran
Ryon, Krista
Young, Benjamin
Bhattacharya, Chandrima
Ng, Dianna L
Granados, Andrea C
Santos, Yale A
Servellita, Venice
Federman, Scot
Ruggiero, Phyllis
Fungtammasan, Arkarachai
Chin, Chen-Shan
Pearson, Nathaniel M
Langhorst, Bradley W
Tanner, Nathan A
Kim, Youngmi
Reeves, Jason W
Hether, Tyler D
Warren, Sarah E
Bailey, Michael
Gawrys, Justyna
Meleshko, Dmitry
Xu, Dong
Couto-Rodriguez, Mara
Nagy-Szakal, Dorottya
Barrows, Joseph
Wells, Heather
O'Hara, Niamh B
Rosenfeld, Jeffrey A
Chen, Ying
Steel, Peter A D
Shemesh, Amos J
Xiang, Jenny
Thierry-Mieg, Jean
Thierry-Mieg, Danielle
Iftner, Angelika
Bezdan, Daniela
Sanchez, Elizabeth
Campion, Thomas R Jr
Sipley, John
Cong, Lin
Craney, Arryn
Velu, Priya
Melnick, Ari M
Shapira, Sagi
Hajirasouliha, Iman
Borczuk, Alain
Iftner, Thomas
Salvatore, Mirella
Loda, Massimo
Westblade, Lars F
Cushing, Melissa
Wu, Shixiu
Levy, Shawn
Chiu, Charles
Schwartz, Robert E
Tatonetti, Nicholas
Rennert, Hanna
Imielinski, Marcin
Mason, Christopher E

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