1. Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions
- Author
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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 AD, Shemesh, Amos J, Xiang, Jenny, Thierry-Mieg, Jean, Thierry-Mieg, Danielle, Iftner, Angelika, Bezdan, Daniela, Sanchez, Elizabeth, Campion, Thomas R, 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, and Mason, Christopher E
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Infectious Diseases ,Vaccine Related ,Biodefense ,Rare Diseases ,Emerging Infectious Diseases ,Clinical Research ,Prevention ,Lung ,Pneumonia & Influenza ,Aetiology ,Development of treatments and therapeutic interventions ,2.1 Biological and endogenous factors ,5.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Aged ,Angiotensin Receptor Antagonists ,Angiotensin-Converting Enzyme Inhibitors ,Antiviral Agents ,COVID-19 ,COVID-19 Nucleic Acid Testing ,Drug Interactions ,Female ,Gene Expression Profiling ,Genome ,Viral ,HLA Antigens ,Host Microbial Interactions ,Humans ,Male ,Middle Aged ,Molecular Diagnostic Techniques ,New York City ,Nucleic Acid Amplification Techniques ,Pandemics ,RNA-Seq ,SARS-CoV-2 ,COVID-19 Drug Treatment - 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.
- Published
- 2021