UK trial shows Dexamethasone can successfully reduce the mortality rate in high risk COVID patients

Authors: Maryam Borumand and Yasmin Dhuga

The RECOVERY trial has shown that dexamethasone can significantly reduce the mortality rates in high risk COVID patients. It may be that by increasing levels of ACE, Dexamethasone can counteract the damage caused by the Coronavirus to the heart and circulatory system, reducing the risk of heart failure. 

The RECOVERY trial was set up in March 2020 and is the world's largest trial trying to find a successful treatment regime against COVID-19:

  • The trial ran across 175 NHS hospitals

  • Over 10,000 patients participated in the trial

  • Participants were randomized to one of 6 treatment arms; 2100 participants took 6mg of Dexamethasone daily for 10 days [1,2]. 

Dexamethasone was found to significantly reduce mortality rates in high risk patients including those on ventilators (by a third) and those receiving oxygen therapy (by a fifth). No one reported any adverse effects from taking dexamethasone. However, dexamethasone was not found to benefit those who did not require oxygen, and this study was only carried out in a hospital setting [1,2]. 

Read the full RECOVERY Trial article.

Administration of dexamethasone 4 to 6 mg every 12 h given intravenously or intramuscularly does not interfere with cortisol levels [3]. Other studies have shown a beneficial effect of steroids in patients in terms of ability to discontinue vasopressors, wean patients from mechanical ventilation, and improve survival [4]

Ventilator machine with lung

Dexamethasone is commonly used to reduce inflammation. A previous study suggests dexamethasone can effectively induce Angiotensin Converting Enzyme (ACE) expression in smooth muscle cells [5]. ACE  protein is known to be involved in pathophysiology of Covid-19 infection, hence by increasing its expression, dexamethasone may play a role in reversing adverse effects of Covid-induced respiratory distress syndrome.

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Dexamethasone affect on ACE
Line graph shows dexamethasone dose response for induction of angiotensin-converting enzyme (ACE) activity in rat aortic smooth muscle cells (RASMCs) and bovine aortic endothelial cells (BAECs).

References:

1- Ledford, H., 2020. Coronavirus Breakthrough: Dexamethasone Is First Drug Shown To Save Lives. [Online] Available at: https://www.nature.com/articles/d41586-020-01824-5 [Accessed 17 June 2020].

2- Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. RECOVERY Trial (Randomised Evaluation of COVID-19 Therapy). [Online] Available from: https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-1 [Accessed 17 June 2020].

3- Shenker & Skatrud. Adrenal insufficiency in critically ill patients. American Journal of Respiratory and Critical Care Medicine. 2001;163:1520-1523

4- Nieboer P, van der Werf TS, Beentjes JAM, et al. Catecholamine dependency in a polytrauma patient: relative adrenal insufficiency? Intensive Care Med. 2000:26(125:127)

5- Fishel et al. Glucocorticoids induce Angiotensin-Converting Enzyme Expression in Vascular Smooth Muscle. Hypertension. 1995;23:343-349


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