In the history of medicine, there have been many major discoveries that were made serendipitously. Drugs which have been developed to treat one illness have proven effective for quite another. This apparently haphazard nature of medical discovery gives rise to what can appear to be a random walk of medical progress, a phenomenon which is captured in the RMS LifeRisks longevity model.
Dexamethasone belongs to a class of medicines known as corticosteroids, or more simply, steroids. It is used to treat a variety of allergic and inflammatory conditions, including, for example, Crohn’s disease and rheumatoid arthritis. This drug is globally available and inexpensive. It is known that excessive inflammatory response is a cause of deterioration of COVID-19 patients in hospital. Accordingly, dexamethasone was considered as a possible treatment for particularly sick COVID-19 patients.
In March 2020, the RECOVERY (Randomized Evaluation of Covid-19 thERapY) trial was established at Oxford University as a randomized clinical trial to test a range of potential treatments for COVID-19, including dexamethasone. Over 11,500 patients were enrolled from 175 U.K. hospitals. On June 8, recruitment to this trial was halted – for positive reasons.
A total of 2,104 COVID-19 patients were randomized to receive six milligrams of dexamethasone once per day for ten days, either by mouth or by intravenous injection. These patients were compared with 4,321 patients randomized to have just the usual care. Among those who received usual care alone, 28-day mortality was highest in those requiring ventilation (41%); intermediate in those requiring oxygen only (25%); and lowest among those who did not require any respiratory intervention (13%).
The trial has shown that dexamethasone reduced deaths by one-third in ventilated patients, and by one-fifth in other patients receiving oxygen only. Prof. Peter Horby, one of the chief investigators, commented: “Dexamethasone is the first drug to be shown to improve survival in COVID-19. The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment.”
However, it should be noted that on June 4, the Oxford University recovery trial concluded that there was no clinical benefit to hospitalized patients with COVID-19 from use of the malaria drug hydroxychloroquine.
Ultimately, there will be a cocktail of drugs for effective treatment of COVID-19. Success in developing this cocktail of drugs for COVID-19 may help encourage the future pandemic insurance market. Whereas dexamethasone treats the inflammation in sick COVID-19 patients, Remdesivir treats the disease at an early stage by preventing the SARS-CoV-2 virus from replicating. If Remdesivir is used early enough, it can reduce recovery time. According to a White House statement issued at the end of April by Dr. Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, “The data shows that remdesivir has a clear-cut, significant, positive effect in diminishing time to recovery.”
On May 1, FDA issued emergency use authorization for Remdesivir. For a new drug, this was very rapid progress. Only three months had elapsed since Remdesivir was given for compassionate use in January to the first U.S. patient to be hospitalized with COVID-19. He recovered. But he might have recovered anyway, and whilst there is evidence suggesting that Remdesivir will save lives, expanded clinical trials will be in progress over the coming months to assess the optimal timing and dosage for Remdesivir treatment.
It took seven years after HIV was first discovered before the first drug AZT was approved by the U.S. Food and Drug Administration (FDA). The FDA approved dexamethasone in 1958! Right from the start of the coronavirus crisis, it was well appreciated by medical experts that we would need such good fortune in the battle against COVID-19. This luck has turned up.
