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

Cell Syst. 2021 Jan 20;12(1):23-40.e7. doi: 10.1016/j.cels.2020.10.003. Epub 2020 Oct 8.


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 ( enabling interactive exploration of our compendium and illustrate its utility through a machine learning approach for prediction of COVID-19 severity.

Keywords: ARDS; COVID-19; ICU; RNA sequencing; machine learning; mass spectrometry; multi-omics; outcomes; severity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19 / blood*
  • COVID-19 / genetics*
  • COVID-19 / therapy
  • Cohort Studies
  • Female
  • Gelsolin / blood
  • Gelsolin / genetics
  • Humans
  • Inflammation Mediators / blood
  • Machine Learning*
  • Male
  • Middle Aged
  • Neutrophils / metabolism
  • Principal Component Analysis / methods
  • Sequence Analysis, RNA / methods*
  • Severity of Illness Index*


  • Gelsolin
  • Inflammation Mediators