Endothelial Function, Inflammation and Organ Dysfunction in 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.

There is very little knowledge of underlying pathogenesis in patients with COVID-19 and
vasodilatory shock. Therefore, the investigators aim to investigate serial changes of
relevant biomarkers in this population to give further understanding of this disease and
to investigate the association with clinically important outcomes. The data will serve to
develop strategies for individualized management of this high-risk group.