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.