Comparison of host endothelial, epithelial and inflammatory response in ICU patients with and without COVID-19: a prospective observational cohort study
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
Affiliations
Pavan K. Bhatraju
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Eric D. Morrell
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Leila Zelnick
Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington
Neha A. Sathe
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Xin-Ya Chai
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Sana S. Sakr
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Sharon K. Sahi
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Anthony Sader
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Dawn M. Lum
Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington
Ted Liu
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Neall Koetje
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Ashley Garay
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Elizabeth Barnes
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Jonathan Lawson
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Gail Cromer
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Mary K. Bray
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Sudhakar Pipavath
Department of Radiology, University of Washington
Bryan R. Kestenbaum
Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington
W. Conrad Liles
Sepsis Center of Research Excellence – University of Washington (SCORE-UW)
Susan L. Fink
Department of Laboratory Medicine and Pathology, University of Washington
T. Eoin West
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Laura Evans
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
Carmen Mikacenic
Translational Research, Benaroya Research Institute
Mark M. Wurfel
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington
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.
