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.

ISSN

2639-8028

Included in

Epidemiology Commons

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