Coronavirus (15) Dexamethasone: the world's first approved COVID-19 drug (e)

Yesterday in the daily coronavirus briefing, the UK government reported an encouraging finding that dexamethasone reduces the COVID-19 mortality rate, and authorised the use of this drug for severely ill COVID-19 patients who required oxygen, including those on mechanical ventilators.¹ Most of you must have read a lot about the preliminary results from the clinical trial RECOVERY (Randomized Evaluation of COVID-19 Therapy) led by the University of Oxford.² I am not going to repeat what the news has reported these two days. Here I would rather like to explain the mechanism of the drug and explain why it is important not to try to buy the drug and take it home for COVID-19 treatment.

Dexamethasone is a synthetic corticosteroid (steroid) among the most popular drugs being tested for COVID-19. It has been used since 1960 to treat people suffering from a variety of conditions relating to inflammation, such as some skin conditions, arthritis, asthma, and inflammatory bowel disease.

The drug suppresses inflammation by inhibiting the expression of many inflammatory mediators, the cells of the immune system. Severely ill COVID-19 patients who need oxygen suffer from an over-reaction of the immune system, called a cytokine storm, which causes lung injury and multi-organ failure, and can be deadly.³ The suppressive effect on the immune system by dexamethasone helps to calm down the cytokine storm. This explains why the drug can significantly reduce deaths in ventilated patients and the patients in need of oxygen.

The clinical trial result showed that the drug only works in severe cases while having little effect on COVID-19 patients with lesser symptoms of the disease. This is because the patients with less severity are not affected by over-reaction of the immune system. The application of the drug thus has no benefit for these patients.

It is also notable that the clinical trial RECOVERY used "low dose" of the dexamethasone for "up to 10 days" on the patients.² This is because previous experiences showed that higher cumulative doses and longer treatment durations of corticosteroids are more likely to develop osteonecrosis in SARS patients.⁴ In fact, in general practice, clinicians would avoid long-term prescription of the drug, and the drug tapered quickly if the patient is improving.⁵

The drug has no life-threatening side effects. However, patients with chronic use of the drug are usually monitored for mood changes, development of osteoporosis, weight gain, hyperglycemia, electrolyte changes, and depression.⁵ Moreover, the use of the drug is contraindicated if patients have systemic fungal infections, hypersensitivity to dexamethasone, or cerebral malaria.⁵

In addition to the side effects it can cause and the contraindication, the use of the drug in early treatment of patients infected with coronaviruses has shown association with a higher subsequent plasma viral load.^6,7 This seems to indicate that the drug's ability to reduce the immune response could also reduce the inflammatory response and prolong the viral load.

The drug is cheap and people can buy the drug on prescription for use with other conditions. However, we should not try to buy it and take it home for COVID-19 treatment, as it showed no effect on patients with no critical symptoms. Even for the severely ill patients, the right dose, the right timing, the right length of treatment, and the knowledge of the contraindications are important if the drug is to be beneficial to the patients.

References

1. "World first coronavirus treatment approved for NHS use by government" Department of Health and Social Care, UK, 16 June, 2020. https://www.gov.uk/government/news/world-first-coronavirus-treatment-approved-for-nhs-use-by-government

2. Low-cost dexamethasone reduces death by up to one third in hospitalised patients with severe respiratory complications of COVID-19. RECOVERY news, 16 June 2020. https://www.recoverytrial.net/news/low-cost-dexamethasone-reduces-death-by-up-to-one-third-in-hospitalised-patients-with-severe-respiratory-complications-of-covid-19

3. X. Zhang, Y. Tan, Y. Ling, et al. Viral and host factors related to the clinical outcome of COVID-19. Nature, 2020 May 20. doi: 10.1038/s41586-020-2355-0

4. R. Zhao, H. Wang, X. Wang, et al. Steroid therapy and the risk of osteonecrosis in SARS patients: a dose-response meta-analysis. Osteoporos Int, 2017 Mar;28(3):1027-1034.

5. D.B. Johnson, M.J. Lopez, and B. Kelley. Dexamethasone. 2020 Apr 27. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. PMID: 29489240

6. N. Lee, K.C. Chan, S. Hui, et al. Effects of early corticosteroid treatment on plasma SARS-associatedCoronavirusRNA concentrations in adult patients. Journal of Clinical Virology, 31 (2004) 304-309.

7. Y.M. Arabi, Y. Mandourah, F. Al-Hameed, et al. Corticosteroid therapy for critically ill patients with middle east respiratory syndrome. Am J Respir Crit Care Med., 2018; 197: 757-767.