Endothelial Function, Inflammation, and Organ Dysfunction in Critically Ill Patients With COVID-19

COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients requiring admission to an intensive care unit. In critically ill patients infected with COVID-19, acute respiratory distress syndrome (ARDS) is found in 40%, 11.9% required continuous renal replacement therapy (RRT), and 13.4% had vasodilatory shock.

Currently, supportive treatment is the mainstay treatment, with fluid administration and vasopressors for haemodynamic support and lung-protective ventilation in patients with severe respiratory failure.3 Targeted drugs, antiviral therapies, and vaccines are still currently being developed, but there is currently insufficient evidence to recommend any drug over another.

Dysregulation of vasomotor tone and alteration of microcirculatory function are common in patients infected with COVID-19. The underlying pathophysiology and contributing factors are unknown. The association with subsequent organ dysfunction and outcome is also unclear.

Circulating bio-adrenomedullin regulates vascular tone and endothelial permeability during sepsis, and has been shown to associate with 28-day mortality, vasopressor requirement, RRT, and positive fluid balance. Proenkephalin is a biomarker of glomerular function, and was shown to elevate in patients with acute kidney injury (AKI), especially in those with persistent AKI, and major adverse kidney events. Dipeptidyl peptidase 3 (DPP-3) is a myocardial depressant factor, which is involved in angiotensin II cleavage. High DPP-3 levels were associated with severe organ dysfunction and short-term mortality. In critically ill patients, COVID-19 has been reported to be associated with cardiovascular dysfunction and high mortality.

The renin-angiotensin-aldosterone system (RAAS) may be linked to the pathogenesis of COVID-19. The coronavirus receptor utilizes angiotensin converting enzyme 2 (ACE2) to enter target cells. Endogenous angiotensin II is hypothesized to prevent binding of coronavirus to ACE2, causing internalization and downregulation of ACE2, and causing lysosome-mediated destruction of ACE2. There are no human studies in COVID-19 patients to confirm this hypothesis yet.