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Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-021-21361-7

2041-1723

Daniel Butler, Christopher Mozsary, Cem Meydan, Jonathan Foox, Joel Rosiene, Alon Shaiber, David Danko, Ebrahim Afshinnekoo, Matthew MacKay, Fritz J. Sedlazeck, Nikolay A. Ivanov, Maria A. Sierra, Diana Pohle, Michael Zietz, Undina Gisladottir, Vijendra Ramlall, Evan Sholle, Edward J. Schenck, Craig Westover, Ciaran Hassan, Krista Ryon, Benjamin Young, Chandrima Bhattacharya, Dianna L. Ng, Andrea Granados, Yale A. Santos, Venice Servellita, Scot Federman, Phyllis Ruggiero, Arkarachai Fungtammasan, Chen-Shan Chin, Nathaniel M. Pearson, Bradley W. Langhorst, Nathan A. Tanner, Young Mi Kim, Jason Reeves, Tyler Hether, Sarah Warren, Michael Bailey, Justyna Gawrys, Dmitry Meleshko, Dong Xu, Mara Couto-Rodriguez, Dorottya Nagy-Szakál, Joseph Barrows, Heather Wells, Niamh B. O’Hara, Jeffrey Rosenfeld, Ying Chen, Peter Steel, Amos Shemesh, Jenny Xiang, Jean Thierry‐Mieg, Danielle Thierry‐Mieg, Angelika Iftner, Daniela Bezdan, Elizabeth Sánchez, Thomas R. Campion, John Sipley, Lin William Cong, Arryn Craney, Priya Velu, Ari Melnick, Sagi Shapira, Iman Hajirasouliha, Alain Borczuk, Thomas Iftner, Mirella Salvatore, Massimo Loda, Lars F. Westblade, Melissa M. Cushing, Shixiu Wu, Shawn Levy, Charles Y. Chiu, Robert E. Schwartz, Nicholas P. Tatonetti, Hanna Rennert, Marcin Imieliński, Christopher E. Mason,

SARS-CoV-2 detection and testing

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.