Article ; Online: Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions.
2021 Volume 12, Issue 1, Page(s) 1660
Abstract: ... LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs and a large-scale shotgun ... by SARS-CoV-2 highlights clinical needs to detect infection, track strain evolution, and identify ... metatranscriptomics platform (total-RNA-seq) for host, viral, and microbial profiling. We applied these methods ...
| 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. |
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| MeSH term(s) | Adult ; Aged ; Angiotensin Receptor Antagonists/pharmacology ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Antiviral Agents/pharmacology ; COVID-19/epidemiology ; COVID-19/genetics ; COVID-19/virology ; COVID-19 Nucleic Acid Testing ; Drug Interactions ; Female ; Gene Expression Profiling ; Genome, Viral ; HLA Antigens/genetics ; Host Microbial Interactions/drug effects ; Host Microbial Interactions/genetics ; Humans ; Male ; Middle Aged ; Molecular Diagnostic Techniques ; New York City/epidemiology ; Nucleic Acid Amplification Techniques ; Pandemics ; RNA-Seq ; SARS-CoV-2/classification ; SARS-CoV-2/drug effects ; SARS-CoV-2/genetics ; COVID-19 Drug Treatment |
| Chemical Substances | Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Antiviral Agents ; HLA Antigens |
| Language | English |
| Publishing date | 2021-03-12 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-021-21361-7 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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