Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19

• Main Authors: Charland, N.C (Author), Filbin, M.R (Author), Goldberg, M.B (Author), Gonye, A.L.K (Author), Gushterova, I. (Author), Hacohen, N. (Author), Kays, K.R (Author), Khanna, H.K (Author), LaSalle, T.J (Author), Lavin-Parsons, K.M (Author), Leisman, D.E (Author), Lilley, B.M (Author), Lodenstein, C.L (Author), Manakongtreecheep, K. (Author), Margolin, J.D (Author), McKaig, B.N (Author), Mehta, A. (Author), Parry, B.A (Author), Rojas-Lopez, M. (Author), Russo, B.C (Author), Sade-Feldman, M. (Author), Sharma, N. (Author), Tantivit, J. (Author), Thomas, M.F (Author), Thompson, B.T (Author), Villani, A.-C (Author)
• Format: Article
• Language: English
• Published: American Thoracic Society 2022
• Subjects: adult; Adult; advanced glycation end product receptor; aged; Aged; Alveolar epithelial cells; Alveolar Epithelial Cells; angiopoietin 2; angiotensin converting enzyme 2; antiviral therapy; Article; artificial ventilation; assisted ventilation; biological marker; Biomarkers; breathing; C reactive protein; cohort analysis; controlled study; coronavirus disease 2019; COVID-19; creatinine; critical care outcome; Critical Care Outcomes; D dimer; dendritic cell lysosome associated membrane protein; disease association; disease course; disease severity; emergency ward; endothelium; Endothelium; endothelium injury; female; Female; hepatitis A virus cellular receptor 1; human; Humans; injury; intercellular adhesion molecule 1; invasive ventilation; lung alveolus; lung alveolus cell; lung alveolus epithelium cell; major clinical study; male; Male; mean arterial pressure; middle aged; Middle Aged; noninvasive ventilation; observational study; organ injury; oxygen saturation; pathophysiology; patient acuity; Patient Acuity; Pulmonary Alveoli; pulse oximetry; remdesivir; renin angiotensin aldosterone system; Renin-angiotensin system; Renin-Angiotensin System; Respiration, Artificial; respiratory distress syndrome; Respiratory distress syndrome; Respiratory Distress Syndrome; respiratory failure; SARS-CoV-2; Sequential Organ Failure Assessment Score; single blind procedure; steroid; tocilizumab; troponin I; ventilated patient; World Health Organization
• Online Access: View Fulltext in Publisher
• Physical Description: 13
• ISBN: 1073449X (ISSN)
• DOI: 10.1164/rccm.202106-1514OC

Rationale: Alveolar and endothelial injury may be differentially associated with coronavirus disease (COVID-19) severity over time. Objectives: To describe alveolar and endothelial injury dynamics and associations with COVID-19 severity, cardiorenovascular injury, and outcomes. Methods: This single-center observational study enrolled patients with COVID-19 requiring respiratory support at emergency department presentation. More than 40 markers of alveolar (including receptor for advanced glycation endproducts [RAGE]), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, and troponin-I) were serially compared between invasively and spontaneously ventilated patients using mixed-effects repeated-measures models. Ventilatory ratios were calculated for intubated patients. Associations of biomarkers with modified World Health Organization scale at Day 28 were determined with multivariable proportional-odds regression. Measurements and Main Results: Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.80-fold higher in invasive ventilation patients at Day 0 (95% confidence interval [CI], 1.50–2.17) versus spontaneous ventilation, but decreased over time in all patients. Changes in alveolar markers did not correlate with changes in endothelial, cardiac, or renal injury markers. In contrast, endothelial markers were similar to lower at Day 0 for invasive ventilation versus spontaneous ventilation, but then increased over time only among intubated patients. In intubated patients, angiopoietin-2 was similar (fold difference, 1.02; 95% CI, 0.89–1.17) to nonintubated patients at Day 0 but 1.80-fold higher (95% CI, 1.56–2.06) at Day 3; cardiorenovascular injury markers showed similar patterns. Endothelial markers were not consistently associated with ventilatory ratios. Endothelial markers were more often significantly associated with 28-day outcomes than alveolar markers. Conclusions: Alveolar injury markers increase early. Endothelial injury markers increase later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to disease progression in severe COVID-19. Copyright © 2022 by the American Thoracic Society.