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

Nat Commun. 2021 Mar 12;12(1):1660. doi: 10.1038/s41467-021-21361-7.

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.

Publication types

  • 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.

MeSH terms

  • Adult
  • Aged
  • Angiotensin Receptor Antagonists / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Antiviral Agents / pharmacology
  • COVID-19 / drug therapy
  • 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*

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antiviral Agents
  • HLA Antigens

Supplementary concepts

  • COVID-19 drug treatment
  • LAMP assay