Severe COVID-19

COVID-19 is a disease resulting from the infection of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Patients developing the severe form of COVID-19, present with low blood oxygen, breathing difficulty and important radiological changes. These patients may experience rapid clinical deterioration, frequently require supportive oxygen therapy, and may progress to respiratory failure requiring mechanical ventilation or death.

Vascular Injury and the Pulmonary Circulation in COVID-19

Recent evidence suggests that COVID-19 as a disease has an important vascular component, as:

  • SARS-CoV-2 infection results in important and widespread vascular injury in the lung, and in other organs,
  • Patients with a history of vascular disease and endothelial dysfunction (e.g.those with hypertension, congestive heart failure and diabetes mellitus) are at an increased risk of developing more severe forms of COVID-19,
  • There is an indication that hypoxia is the result of a ventilation-perfusion mismatch, that is less affected areas of the lungs do not participate in the abosrption of oxygen,
  • There is an increasing awareness that pulmonary-hypertension like conditions are observed in patients with severe COVID-19, with right-heart strain and failure a frequent finding post-infection and post-mortem.

Endothelin in Acute Lung Injury, Viral Pneumonia and ARDS

There is pre-clinical and clinical evidence that Endothelin plays a role in regulating pulmonary blood flow in Acute Lung Injury. In models of Acute Lung Injury, Endothelin receptor blockade results in a rapid and significant increase in blood oxygen concentration. Increased Endothelin activity has been described in models of Viral Pneumonia and hypoxia. Endothelin receptor blocakde has been shown to prevent some of the key features of Viral Pneumonia progression as well as increase animal surivival in models of Influenza Viral Pneumonia. Finally, patients developing ARDS have increased levels of Endothelin, and persistent increased levels of Endothelin have been observed in patients with Acute Respiratory Distress Syndrome (ARDS) and adverse outcomes.

Micro-dose Ambrisentan in Severe COVID-19

To determine if micro-dose Ambrisentan is safe and of clinical benefit in Severe COVID-19, Noorik has initiated a Phase II multi-center, randomised, placebo-controlled study in high-risk patients. The primary objectives of the study are to determine changes in oxygen saturation in the first 72 hours following hospital admission and the rate of progression to respiratory failure at 14 days. The study is ongoing.


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