COVID-19 disease severity may be related to alveolar and endothelial damage in diverse ways throughout time. To investigate the dynamics of alveolar and endothelial injury and their links to COVID-19 severity, cardiorenovascular injury, and outcomes, COVID-19 patients requiring respiratory support at the emergency department were enrolled in this single-center observational trial. Researchers serially evaluated by using mixed-effects repeated-measures models, >40 indicators of alveolar (including RAGE), endothelium (including angiopoietin-2), and cardiorenovascular injury (including renin, kidney injury molecule-1, troponin-I) between invasively and spontaneously ventilated individuals. Intubated patients’ ventilation ratios were calculated. 

On Day 28, multivariable proportional-odds regression was used to investigate biomarker associations with the modified World Health Organization scale. At Day 0, 74 (33%) of the 225 patients required invasive ventilation. RAGE was 1.81-fold greater in these patients on Day 0 (95%CI: 1.53-2.15). However, it decreased in all patients throughout time. Endothelial, cardiac, and renal damage markers did not change with changes in alveolar characteristics. On the other hand, invasive ventilation had similar-to-lower endothelial markers at Day 0 but rose over time. Angiopoietin-2 was 0.86-fold lower (95%CI: 0.76-0.96) in intubated patients on Day 0 than non-intubated patients on Day 3, but 1.49-fold greater (95%CI: 1.32-1.67) on Day 3; cardiorenovascular damage indicators exhibited similar trends. Endothelial indicators did not appear to be consistently linked to ventilatory ratios. Endothelial markers were more often than alveolar indicators to correlate with 28-day outcomes significantly. Early alveolar injury markers rise. Endothelial injury markers rise later and are linked to cardiorenovascular injury as well as the 28-day yield. COVID-19 is likely caused by alveolar and endothelial damage at distinct stages.