Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer's and coronary disease pathways

Lihua Wang, Daniel Western, Jigyasha Timsina, Charlie Repaci, Won Min Song, Joanne Norton, Pat Kohlfeld, John Budde, Sharlee Climer, Omar H. Butt, Daniel Jacobson, Michael Garvin, Alan R. Templeton, Shawn Campagna, Jane O'Halloran, Rachel Presti, Charles W. Goss, Philip A. Mudd, Beau M. Ances, Bin ZhangYun Ju Sung, Carlos Cruchaga

Research output: Contribution to journalArticlepeer-review


Identification of proteins dysregulated by COVID-19 infection is critically important for better understanding of its pathophysiology, building prognostic models, and identifying new targets. Plasma proteomic profiling of 4,301 proteins was performed in two independent datasets and tested for the association for three COVID-19 outcomes (infection, ventilation, and death). We identified 1,449 proteins consistently associated in both datasets with any of these three outcomes. We subsequently created highly accurate models that distinctively predict infection, ventilation, and death. These proteins were enriched in specific biological processes including cytokine signaling, Alzheimer's disease, and coronary artery disease. Mendelian randomization and gene network analyses identified eight causal proteins and 141 highly connected hub proteins including 35 with known drug targets. Our findings provide distinctive prognostic biomarkers for two severe COVID-19 outcomes, reveal their relationship to Alzheimer's disease and coronary artery disease, and identify potential therapeutic targets for COVID-19 outcomes.

Original languageEnglish
Article number106408
Issue number4
StatePublished - 21 Apr 2023
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: ) and the Departments of Neurology and Psychiatry at Washington University School of Medicine.

Funding Information:
The recruitment and clinical characterization of research participants at Washington University were supported by NIH P30AG066444 (JCM), P01AG03991 (JCM), and P01AG026276 (JCM).

Funding Information:
This study utilized samples obtained from the Washington University School of Medicine’s COVID-19 biorepository, which is supported by: the Barnes-Jewish Hospital Foundation ; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the National Institutes of Health ; and the Washington UniversityInstitute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health . The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH.

Funding Information:
This work was supported by grants from the National Institutes of Health ( RF1AG074007 (YJS), R01AG044546 (CC), P01AG003991 (CC, JCM), RF1AG053303 (CC, SC), RF1AG058501 (CC), and U01AG058922 (CC), Alzheimer's Association Research Grant 925002 (SC), the Chan Zuckerberg Initiative (CZI), and the Alzheimer's Association Zenith Fellows Award ( ZEN-22-848604 , awarded to CC).

Funding Information:
C.C. has received research support from: Biogen, EISAI, Alector, GSK, an anonymous foundation and Parabon. The funders of the study had no role in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. C.C. is a member of the advisory board of Vivid Genomics, and Circular Genomics and own stocks.

Publisher Copyright:
© 2023 The Author(s)


  • Biochemistry
  • Biological sciences
  • Disease
  • Protein

ASJC Scopus subject areas

  • General


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