Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study
Year: 2021
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Analyses of blood biomarkers involved in the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection can reveal distinct biological pathways and inform development and testing of therapeutics for COVID-19. Our objective was to evaluate host endothelial, epithelial and inflammatory biomarkers in COVID-19. METHODS: We prospectively enrolled 171 ICU patients, including 78 (46%) patients positive and 93 (54%) negative for SARS-CoV-2 infection from April to September, 2020. We compared 22 plasma biomarkers in blood collected within 24 h and 3 days after ICU admission. RESULTS: In critically ill COVID-19 and non-COVID-19 patients, the most common ICU admission diagnoses were respiratory failure or pneumonia, followed by sepsis and other diagnoses. Similar proportions of patients in both groups received invasive mechanical ventilation at the time of study enrollment. COVID-19 and non-COVID-19 patients had similar rates of acute respiratory distress syndrome, severe acute kidney injury, and in-hospital mortality. While concentrations of interleukin 6 and 8 were not different between groups, markers of epithelial cell injury (soluble receptor for advanced glycation end products, sRAGE) and acute phase proteins (serum amyloid A, SAA) were significantly higher in COVID-19 compared to non-COVID-19, adjusting for demographics and APACHE III scores. In contrast, angiopoietin 2:1 (Ang-2:1 ratio) and soluble tumor necrosis factor receptor 1 (sTNFR-1), markers of endothelial dysfunction and inflammation, were significantly lower in COVID-19 (p < 0.002). Ang-2:1 ratio and SAA were associated with mortality only in non-COVID-19 patients. CONCLUSIONS: These studies demonstrate that, unlike other well-studied causes of critical illness, endothelial dysfunction may not be characteristic of severe COVID-19 early after ICU admission. Pathways resulting in elaboration of acute phase proteins and inducing epithelial cell injury may be promising targets for therapeutics in COVID-19.
Source: Critical Care
Authors: Pavan K. Bhatraju, Eric D. Morrell, Leila Zelnick, Neha A. Sathe, Xin-Ya Chai, Sana S. Sakr, Sharon K. Sahi, Anthony Sader, Dawn M. Lum, Ted Liu, Neall Koetje, Ashley Garay, Elizabeth Barnes, Jonathan Lawson, Gail Cromer, Mary K. Bray, Sudhakar Pipavath, Bryan R. Kestenbaum, W. Conrad Liles, Susan L. Fink, T. Eoin West, Laura Evans, Carmen Mikacenic, Mark M. Wurfel
Institutions: University of Washington, Benaroya Research Institute
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,490
Funders: Bill and Melinda Gates Foundation, Firland Foundation, F. Hoffmann-La Roche, University of Washington, Northwest Kidney Centers, Centers for Disease Control and Prevention Foundation, National Institutes of Health, Centers for Disease Control and Prevention, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: University of Washington Foundation - to improve our understanding of Covid-19, which will inform the development of medicines to treat the disease, Role of Kidney Proximal Tubular Secretion in Critical Illness, The Assessment of Acute Kidney Injury Sub-phenotypes in the Intensive Care Unit, Role of Ire1alpha in Resistance to Viral-Induced Apoptosis, The Role of Alveolar Mononuclear Phagocytes in Acute Respiratory Distress Syndrome, Midcareer Investigator Award: Metabolic Complications of Chronic Kidney Disease
OpenAlex ID: W3153597520