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

TitleShotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.
Publication TypeJournal Article
Year of Publication2021
AuthorsButler D, Mozsary C, Meydan C, Foox J, Rosiene J, Shaiber A, Danko D, Afshinnekoo E, MacKay M, Sedlazeck FJ, Ivanov NA, Sierra M, Pohle D, Zietz M, Gisladottir U, Ramlall V, Sholle ET, Schenck EJ, Westover CD, Hassan C, Ryon K, Young B, Bhattacharya C, Ng DL, Granados AC, Santos YA, Servellita V, Federman S, Ruggiero P, Fungtammasan A, Chin C-S, Pearson NM, Langhorst BW, Tanner NA, Kim Y, Reeves JW, Hether TD, Warren SE, Bailey M, Gawrys J, Meleshko D, Xu D, Couto-Rodriguez M, Nagy-Szakal D, Barrows J, Wells H, O'Hara NB, Rosenfeld JA, Chen Y, Steel PAD, Shemesh AJ, Xiang J, Thierry-Mieg J, Thierry-Mieg D, Iftner A, Bezdan D, Sanchez E, Campion TR, Sipley J, Cong L, Craney A, Velu P, Melnick AM, Shapira S, Hajirasouliha I, Borczuk A, Iftner T, Salvatore M, Loda M, Westblade LF, Cushing M, Wu S, Levy S, Chiu C, Schwartz RE, Tatonetti N, Rennert H, Imielinski M, Mason CE
JournalNat Commun
Date Published2021 03 12
KeywordsAdult, 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

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.

Alternate JournalNat Commun
PubMed ID33712587
PubMed Central IDPMC7954844
Grant ListR01 MH117406 / MH / NIMH NIH HHS / United States
T15 LM007079 / LM / NLM NIH HHS / United States
TL1 TR002386 / TR / NCATS NIH HHS / United States
U19 AI144297 / AI / NIAID NIH HHS / United States
R35 GM138152 / GM / NIGMS NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
R35 GM131905 / GM / NIGMS NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States
R25 EB020393 / EB / NIBIB NIH HHS / United States
R01 AI151059 / AI / NIAID NIH HHS / United States
Related Faculty: 
Hanna Rennert, Ph.D. Lars Westblade, Ph.D. Massimo Loda, M.D. Melissa Cushing, M.D. Priya Velu, M.D., Ph.D.


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