Alveolar, Endothelial, and Organ Injury Marker Dynamics in Severe COVID-19
American Journal of Respiratory and Critical Care Medicine, 2021
Leisman D., Mehta A., Thompson B., Charland N., Gonye A., Gushterova I., Kays K., Khanna H., LaSalle T., Lavin-Parsons K., Lilley B., Lodenstein C., Manakongtreecheep K., Margolin J., McKaig B., Rojas-Lopez M., Russo B., Sharma N., Tantivit J., Thomas M., Parry B., Villani A., Sade-Feldman M., Hacohen N., Filbin M., Goldberg M.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Rationale: Alveolar and endothelial injury may be differentially associated with COVID-19 disease 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 COVID-19 patients requiring respiratory support at emergency department presentation. >40 markers of alveolar (including RAGE), endothelial (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, 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.
Results: Of 225 patients, 74 (33%) received invasive ventilation at Day 0. RAGE was 1.81-fold higher in these patients at Day 0 (95%CI: 1.53-2.15) 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 for invasive ventilation at Day 0 but increased over time. In intubated patients, angiopoietin-2 was 0.86-fold lower (95%CI: 0.76-0.96) versus non-intubated patients at Day 0 but 1.49-fold higher (95%CI: 1.32-1.67) 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 rise early. Endothelial injury markers rise later and are associated with cardiorenovascular injury and 28-day outcome. Alveolar and endothelial injury likely contribute at different times to severe COVID-19.