Large-Scale Multi-omic Analysis of COVID-19 Severity.

Journal: Cell systems
PMID: 33096026

Abstract

We performed RNA-seq and high-resolution mass spectrometry on 128 blood samples from COVID-19-positive and COVID-19-negative patients with diverse disease severities and outcomes. Quantified transcripts, proteins, metabolites, and lipids were associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many of which were involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a machine learning approach for prediction of COVID-19 severity.

Authors

  • Katherine A Overmyer
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Morgridge Institute for Research, Madison, WI 53562, USA.
  • Evgenia Shishkova
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Ian J Miller
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Joseph Balnis
    Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
  • Matthew N Bernstein
    Department of Computer Sciences.
  • Trenton M Peters-Clarke
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Jesse G Meyer
    Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • Qiuwen Quan
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Laura K Muehlbauer
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Edna A Trujillo
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Yuchen He
    Xiangya School of Medicine, Central South University, ChangSha, 410008, China.
  • Amit Chopra
    Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA.
  • Hau C Chieng
    Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA.
  • Anupama Tiwari
    Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA; Division of Sleep Medicine, Albany Medical Center, Albany, NY 12208, USA.
  • Marc A Judson
    Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA.
  • Brett Paulson
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Dain R Brademan
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Yunyun Zhu
    School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
  • Lia R Serrano
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Vanessa Linke
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Lisa A Drake
    Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
  • Alejandro P Adam
    Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA; Department of Ophthalmology, Albany Medical College, Albany, NY 12208, USA.
  • Bradford S Schwartz
    Morgridge Institute for Research, Madison, WI 53562, USA.
  • Harold A Singer
    Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
  • Scott Swanson
    Morgridge Institute for Research, Madison, WI 53562, USA.
  • Deane F Mosher
    Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA.
  • Ron Stewart
    Morgridge Institute for Research, Regenerative Biology, Madison, WI, USA.
  • Joshua J Coon
    National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Morgridge Institute for Research, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA; Department of Chemistry, University of Wisconsin, Madison, WI 53562, USA. Electronic address: jcoon@chem.wisc.edu.
  • Ariel Jaitovich
    Division of Pulmonary and Critical Care Medicine, Albany Medical Center, Albany, NY 12208, USA; Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA. Electronic address: jaitova@amc.edu.

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