Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity

Authors

• Pavan K. Bhatraju, University of Washington Medical Center
• Eric D. Morrell, University of Washington Medical Center
• Ian B. Stanaway, University of Washington Medical Center
• Neha A. Sathe, University of Washington Medical Center
• Avantika Srivastava, University of Pittsburgh
• Radu Postelnicu, New York University Langone Health
• Richard Green, University of Washington Medical Center
• Adair Andrews, Society of Critical Care Medicine
• Martin Gonzalez, Society of Critical Care Medicine
• Christopher J. Kratochvil, University of Nebraska Medical CenterFollow
• Vishakha K. Kumar, Society of Critical Care Medicine
• Tien-Ying Hsiang, University of Washington
• Michael Gale, University of Washington
• George L. Anesi, University of Pennsylvania
• David Wyles, Denver Health Medical Center
• M. Jana Broadhurst, University of Nebraska Medical CenterFollow
• David Brett-Major, University of Nebraska Medical CenterFollow
• Vikramjit Mukherjee, New York University Langone Health
• Jonathan E. Sevransky, Emory University
• Douglas Landsittel, Indiana University
• Chi Hung, University of Washington Medical Center
• William A Altemeier, University of Washington Medical Center
• Sina A. Gharib, University of Washington Medical Center
• Timothy M. Uyeki, Centers for Disease Control and Prevention
• J. Perren Cobb, University of Southern California
• Janice M. Liebler, University of Southern California
• David R. Crosslin, Tulane University
• Gail P. Jarvik, University of Washington Medical Center
• Leopoldo N. Segal, New York University Langone Health
• Laura Evans, University of Washington Medical Center
• Carmen Mikacenic, Benaroya Research Institute
• Mark M. Wurfel, University of Washington Medical Center

Document Type

Article

Journal Title

Critical Care Explorations

Publication Date

2023

Volume

5

Abstract

IMPORTANCE: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.

OBJECTIVES: To assess the role of ANGPTL4 in COVID-19-related outcomes.

DESIGN SETTING AND PARTICIPANTS: Two hundred twenty-five COVID-19 ICU patients were enrolled from April 2020 to May 2021 in a prospective, multicenter cohort study from three different medical centers, University of Washington, University of Southern California and New York University.

MAIN OUTCOMES AND MEASURES: Plasma ANGPTL4 was measured on days 1, 7, and 14 after ICU admission. We used previously published tissue proteomic data and lung single nucleus RNA (snRNA) sequencing data from specimens collected from COVID-19 patients to determine the tissues and cells that produce ANGPTL4.

RESULTS: Higher plasma ANGPTL4 concentrations were significantly associated with worse hospital mortality (adjusted odds ratio per log

CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

DOI Link

10.1097/CCE.0000000000000827

ISSN

2639-8028

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Recommended Citation

Bhatraju, Pavan K.; Morrell, Eric D.; Stanaway, Ian B.; Sathe, Neha A.; Srivastava, Avantika; Postelnicu, Radu; Green, Richard; Andrews, Adair; Gonzalez, Martin; Kratochvil, Christopher J.; Kumar, Vishakha K.; Hsiang, Tien-Ying; Gale, Michael; Anesi, George L.; Wyles, David; Broadhurst, M. Jana; Brett-Major, David; Mukherjee, Vikramjit; Sevransky, Jonathan E.; Landsittel, Douglas; Hung, Chi; Altemeier, William A; Gharib, Sina A.; Uyeki, Timothy M.; Cobb, J. Perren; Liebler, Janice M.; Crosslin, David R.; Jarvik, Gail P.; Segal, Leopoldo N.; Evans, Laura; Mikacenic, Carmen; and Wurfel, Mark M., "Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity" (2023). Journal Articles: Epidemiology. 178.
https://digitalcommons.unmc.edu/coph_epidem_articles/178