Large-Scale Multi-omic Analysis of COVID-19 Severity.
Katherine A Overmyer, Evgenia Shishkova, Ian J Miller, Joseph Balnis, Matthew N Bernstein, Trenton M Peters-Clarke, Jesse G Meyer, Qiuwen Quan, Laura K Muehlbauer, Edna A Trujillo, Yuchen He, Amit Chopra, Hau C Chieng, Anupama Tiwari, Marc A Judson, Brett Paulson, Dain R Brademan, Yunyun Zhu, Lia R Serrano, Vanessa Linke, Lisa A Drake, Alejandro P Adam, Bradford S Schwartz, Harold A Singer, Scott Swanson, Deane F Mosher, Ron Stewart, Joshua J Coon, Ariel Jaitovich
Author Information
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: Morgridge Institute for Research, Madison, WI 53562, USA.
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: National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, 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: National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA.
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: National Center for Quantitative Biology of Complex Systems, Madison, WI 53562, USA; Department of Biomolecular Chemistry, University of Wisconsin, Madison, WI 53562, USA.
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, Madison, WI 53562, 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.
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.
