Authors: 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.; 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.
Issue: Nat Commun . 2021 Mar 12;12(1):1660.
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.