Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity-Reference-Cited by-同舟云学术

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

Published:2022-12-30 Issue:1 Volume:5 Page:e0827
ISSN:2639-8028
Container-title:Critical Care Explorations
language:en
Short-container-title:

Author:

Bhatraju Pavan K.,Morrell Eric D.¹,Stanaway Ian B.²,Sathe Neha A.¹,Srivastava Avantika³,Postelnicu Radu⁴,Green Richard⁵,Andrews Adair⁶,Gonzalez Martin⁶,Kratochvil Christopher J.⁷,Kumar Vishakha K.⁶,Hsiang Tien-Ying⁸,Gale Michael⁸,Anesi George L.⁹,Wyles David¹⁰,Broadhurst M. Jana⁷,Brett-Major David⁷,Mukherjee Vikramjit⁴,Sevransky Jonathan E.¹¹¹²,Landsittel Douglas¹³,Hung Chi¹,Altemeier William A.¹,Gharib Sina A.¹,Uyeki Timothy M.¹⁴,Cobb J. Perren¹⁵,Liebler Janice M.¹⁶,Crosslin David R.¹⁷,Jarvik Gail P.⁵,Segal Leopoldo N.⁴,Evans Laura¹,Mikacenic Carmen¹⁸,Wurfel Mark M.

Affiliation:

1. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington Medical Center, Seattle, WA.

2. Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington Medical Center, Seattle, WA.

3. Department of Biomedical Informatics, School of Medicine, University of Pittsburgh, Pittsburgh, PA.

4. Division of Pulmonary, Critical Care, and Sleep Medicine, NYU Grossman School of Medicine, NYU Langone Health, New York, NY.

5. Departments of Medicine (Division of Medical Genetics) and Genome Sciences, University of Washington Medical Center, Seattle, WA.

6. Society of Critical Care Medicine, Mount Prospect, IL.

7. Global Center for Health Security, University of Nebraska Medical Center, Omaha, NE.

8. Department of Immunology, University of Washington, Seattle, WA.

9. Division of Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

10. Division of Infectious Diseases, Denver Health Medical Center, Denver, CO.

11. Division of Pulmonary, Allergy, Critical Care and Sleep, School of Medicine, Emory University, Atlanta, GA.

12. Emory Critical Care Center, Emory Healthcare, Atlanta, GA.

13. Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN.

14. Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA.

15. Departments of Surgery and Anesthesiology, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA.

16. Division of Pulmonary, Critical Care and Sleep Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA.

17. Division of Biomedical Informatics and Genomics, John W. Deming Department of Medicine, Tulane University, School of Medicine, New Orleans, LA.

18. Translational Research, Benaroya Research Institute, Seattle, WA.

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 log2 increase, 1.53; 95% CI, 1.17–2.00; p = 0.002). Higher ANGPTL4 concentrations were also associated with higher proportions of venous thromboembolism and acute respiratory distress syndrome. Longitudinal ANGPTL4 concentrations were significantly different during the first 2 weeks of hospitalization in patients who subsequently died compared with survivors (p for interaction = 8.1 × 10–5). Proteomics analysis demonstrated abundance of ANGPTL4 in lung tissue compared with other organs in COVID-19. ANGPTL4 single-nuclear RNA gene expression was significantly increased in pulmonary alveolar type 2 epithelial cells and fibroblasts in COVID-19 lung tissue compared with controls. CONCLUSIONS AND RELEVANCE: ANGPTL4 is expressed in pulmonary epithelial cells and fibroblasts and is associated with clinical prognosis in critically ill COVID-19 patients.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Critical Care and Intensive Care Medicine

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