PMID- 33712587 OWN - NLM STAT- MEDLINE VI - 12 IP - 1 TI - Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions. PG - 1660 LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - Nat Commun JT - Nature communications JID - 101528555 IS - 2041-1723 (Electronic) LID - 10.1038/s41467-021-21361-7 [doi] FAU - Butler, Daniel AU - Butler D AUID- ORCID: 0000-0002-3687-8419 AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Mozsary, Christopher AU - Mozsary C AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Meydan, Cem AU - Meydan C AUID- ORCID: 0000-0002-0663-6216 AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. AD - WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA. FAU - Foox, Jonathan AU - Foox J AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. FAU - Rosiene, Joel AU - Rosiene J AD - New York Genome Center, New York, NY, USA. AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Shaiber, Alon AU - Shaiber A AD - New York Genome Center, New York, NY, USA. AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. AD - Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. FAU - Danko, David AU - Danko D AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Afshinnekoo, Ebrahim AU - Afshinnekoo E AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. AD - WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA. FAU - MacKay, Matthew AU - MacKay M AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Sedlazeck, Fritz J AU - Sedlazeck FJ AUID- ORCID: 0000-0001-6040-2691 AD - Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA. FAU - Ivanov, Nikolay A AU - Ivanov NA AUID- ORCID: 0000-0003-4021-8875 AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. AD - Clinical & Translational Science Center, Weill Cornell Medicine, New York, NY, USA. FAU - Sierra, Maria AU - Sierra M AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. FAU - Pohle, Diana AU - Pohle D AD - Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany. FAU - Zietz, Michael AU - Zietz M AUID- ORCID: 0000-0003-0539-630X AD - Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA. FAU - Gisladottir, Undina AU - Gisladottir U AUID- ORCID: 0000-0001-5892-0852 AD - Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA. FAU - Ramlall, Vijendra AU - Ramlall V AD - Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA. AD - Department of Cellular, Molecular Physiology & Biophysics, Columbia University, Columbia, NY, USA. FAU - Sholle, Evan T AU - Sholle ET AUID- ORCID: 0000-0001-9518-4399 AD - Information Technologies & Services Department, Weill Cornell Medicine, New York, NY, USA. FAU - Schenck, Edward J AU - Schenck EJ AD - Department of Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Westover, Craig D AU - Westover CD AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Hassan, Ciaran AU - Hassan C AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Ryon, Krista AU - Ryon K AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Young, Benjamin AU - Young B AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Bhattacharya, Chandrima AU - Bhattacharya C AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. FAU - Ng, Dianna L AU - Ng DL AD - Department of Laboratory Medicine, University of California, San Francisco, CA, USA. FAU - Granados, Andrea C AU - Granados AC AD - Department of Laboratory Medicine, University of California, San Francisco, CA, USA. AD - UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. FAU - Santos, Yale A AU - Santos YA AD - Department of Laboratory Medicine, University of California, San Francisco, CA, USA. AD - UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. FAU - Servellita, Venice AU - Servellita V AD - Department of Laboratory Medicine, University of California, San Francisco, CA, USA. AD - UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. FAU - Federman, Scot AU - Federman S AUID- ORCID: 0000-0001-8712-3131 AD - Department of Laboratory Medicine, University of California, San Francisco, CA, USA. AD - UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. FAU - Ruggiero, Phyllis AU - Ruggiero P AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Fungtammasan, Arkarachai AU - Fungtammasan A AD - DNAnexus, Inc., Mountain View, CA, USA. FAU - Chin, Chen-Shan AU - Chin CS AD - DNAnexus, Inc., Mountain View, CA, USA. FAU - Pearson, Nathaniel M AU - Pearson NM AD - Root Deep Insight, Boston, MA, USA. FAU - Langhorst, Bradley W AU - Langhorst BW AUID- ORCID: 0000-0001-7390-1094 AD - New England Biolabs, Ipswich, MA, USA. FAU - Tanner, Nathan A AU - Tanner NA AD - New England Biolabs, Ipswich, MA, USA. FAU - Kim, Youngmi AU - Kim Y AD - NanoString Technologies, Seattle, WA, USA. FAU - Reeves, Jason W AU - Reeves JW AD - NanoString Technologies, Seattle, WA, USA. FAU - Hether, Tyler D AU - Hether TD AD - NanoString Technologies, Seattle, WA, USA. FAU - Warren, Sarah E AU - Warren SE AD - NanoString Technologies, Seattle, WA, USA. FAU - Bailey, Michael AU - Bailey M AD - NanoString Technologies, Seattle, WA, USA. FAU - Gawrys, Justyna AU - Gawrys J AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Meleshko, Dmitry AU - Meleshko D AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. AD - Tri-Institutional Computational Biology & Medicine Program, Weill Cornell Medicine, New York, NY, USA. FAU - Xu, Dong AU - Xu D AD - Genomics Resources Core Facility, Weill Cornell Medicine, New York, NY, USA. FAU - Couto-Rodriguez, Mara AU - Couto-Rodriguez M AUID- ORCID: 0000-0002-9799-0068 AD - Biotia, Inc., New York, NY, USA. FAU - Nagy-Szakal, Dorottya AU - Nagy-Szakal D AD - Biotia, Inc., New York, NY, USA. AD - Department of Cell Biology, SUNY Downstate Health Sciences University, New York, NY, USA. FAU - Barrows, Joseph AU - Barrows J AD - Biotia, Inc., New York, NY, USA. FAU - Wells, Heather AU - Wells H AD - Biotia, Inc., New York, NY, USA. FAU - O'Hara, Niamh B AU - O'Hara NB AD - Biotia, Inc., New York, NY, USA. AD - Department of Cell Biology, SUNY Downstate Health Sciences University, New York, NY, USA. FAU - Rosenfeld, Jeffrey A AU - Rosenfeld JA AD - Rutgers Cancer Institute of New Jersey, New York, NJ, USA. AD - Department of Pathology, Robert Wood Johnson Medical School, New York, NJ, USA. FAU - Chen, Ying AU - Chen Y AUID- ORCID: 0000-0002-0072-1567 AD - Rutgers Cancer Institute of New Jersey, New York, NJ, USA. FAU - Steel, Peter A D AU - Steel PAD AD - Department of Emergency Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Shemesh, Amos J AU - Shemesh AJ AUID- ORCID: 0000-0002-1424-2196 AD - Department of Emergency Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Xiang, Jenny AU - Xiang J AD - Genomics Resources Core Facility, Weill Cornell Medicine, New York, NY, USA. FAU - Thierry-Mieg, Jean AU - Thierry-Mieg J AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. FAU - Thierry-Mieg, Danielle AU - Thierry-Mieg D AD - National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA. FAU - Iftner, Angelika AU - Iftner A AD - Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany. FAU - Bezdan, Daniela AU - Bezdan D AUID- ORCID: 0000-0002-1203-8239 AD - Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany. FAU - Sanchez, Elizabeth AU - Sanchez E AD - Department of Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Campion, Thomas R Jr AU - Campion TR Jr AUID- ORCID: 0000-0001-7624-769X AD - Information Technologies & Services Department, Weill Cornell Medicine, New York, NY, USA. AD - Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA. FAU - Sipley, John AU - Sipley J AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Cong, Lin AU - Cong L AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Craney, Arryn AU - Craney A AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Velu, Priya AU - Velu P AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Melnick, Ari M AU - Melnick AM AUID- ORCID: 0000-0002-8074-2287 AD - Department of Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Shapira, Sagi AU - Shapira S AUID- ORCID: 0000-0002-5425-3682 AD - Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA. FAU - Hajirasouliha, Iman AU - Hajirasouliha I AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. AD - Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. FAU - Borczuk, Alain AU - Borczuk A AUID- ORCID: 0000-0001-6807-8064 AD - Department of Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Iftner, Thomas AU - Iftner T AD - Institute of Medical Virology and Epidemiology of Viral Diseases, University Hospital Tuebingen, Tuebingen, Germany. FAU - Salvatore, Mirella AU - Salvatore M AUID- ORCID: 0000-0002-8296-0376 AD - Department of Medicine, Weill Cornell Medicine, New York, NY, USA. AD - Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA. FAU - Loda, Massimo AU - Loda M AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Westblade, Lars F AU - Westblade LF AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. AD - Department of Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Cushing, Melissa AU - Cushing M AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. FAU - Wu, Shixiu AU - Wu S AD - Hangzhou Cancer Institute, Hangzhou Cancer Hospital, Hangzhou, China. AD - Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, China. FAU - Levy, Shawn AU - Levy S AUID- ORCID: 0000-0002-1369-5740 AD - HudsonAlpha Discovery Institute, Huntsville, AL, USA. FAU - Chiu, Charles AU - Chiu C AUID- ORCID: 0000-0003-2915-2094 AD - Department of Laboratory Medicine, University of California, San Francisco, CA, USA. AD - UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, USA. AD - Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, CA, USA. FAU - Schwartz, Robert E AU - Schwartz RE AUID- ORCID: 0000-0002-5417-5995 AD - Department of Medicine, Weill Cornell Medicine, New York, NY, USA. res2025@med.cornell.edu. FAU - Tatonetti, Nicholas AU - Tatonetti N AUID- ORCID: 0000-0002-2700-2597 AD - Department of Biomedical Informatics, Department of Systems Biology, Department of Medicine, Institute for Genomic Medicine, Columbia University, Columbia, NY, USA. npt2105@cumc.columbia.edu. FAU - Rennert, Hanna AU - Rennert H AUID- ORCID: 0000-0002-1759-2562 AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. har2006@med.cornell.edu. FAU - Imielinski, Marcin AU - Imielinski M AUID- ORCID: 0000-0002-2211-4741 AD - New York Genome Center, New York, NY, USA. mai9037@med.cornell.edu. AD - Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA. mai9037@med.cornell.edu. AD - Englander Institute for Precision Medicine and the Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. mai9037@med.cornell.edu. FAU - Mason, Christopher E AU - Mason CE AUID- ORCID: 0000-0002-1850-1642 AD - Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu. AD - The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu. AD - WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu. AD - The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. chm2042@med.cornell.edu. IS - 2041-1723 (Linking) RN - 0 (Angiotensin Receptor Antagonists) RN - 0 (Angiotensin-Converting Enzyme Inhibitors) RN - 0 (Antiviral Agents) RN - 0 (HLA Antigens) SB - IM MH - Adult MH - Aged MH - Angiotensin Receptor Antagonists/pharmacology MH - Angiotensin-Converting Enzyme Inhibitors/pharmacology MH - Antiviral Agents/pharmacology MH - COVID-19/epidemiology/*genetics/*virology MH - COVID-19 Nucleic Acid Testing MH - Drug Interactions MH - Female MH - Gene Expression Profiling MH - Genome, Viral MH - HLA Antigens/genetics MH - Host Microbial Interactions/drug effects/genetics MH - Humans MH - Male MH - Middle Aged MH - Molecular Diagnostic Techniques MH - New York City/epidemiology MH - Nucleic Acid Amplification Techniques MH - Pandemics MH - RNA-Seq MH - SARS-CoV-2/classification/drug effects/*genetics MH - COVID-19 Drug Treatment PMC - PMC7954844 DCOM- 20210322 LR - 20240211 DP - 20210312 DEP - 20210312 AB - 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.