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: 92


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
COVID-19 Drug Treatment


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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