KOR

e-Article

Shotgun transcriptome, spatial omics, and isothermal profiling of SARS-CoV-2 infection reveals unique host responses, viral diversification, and drug interactions
Document Type
article
Source
Nature Communications. 12(1)
Subject
Biological Sciences
Biomedical and Clinical Sciences
Clinical Sciences
Infectious Diseases
Vaccine Related
Biodefense
Rare Diseases
Emerging Infectious Diseases
Clinical Research
Prevention
Lung
Pneumonia & Influenza
Aetiology
Development of treatments and therapeutic interventions
2.1 Biological and endogenous factors
5.1 Pharmaceuticals
Infection
Good Health and Well Being
Adult
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
COVID-19 Drug Treatment
Language
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.