Success with a steroid

In March, a study in Wuhan, China, suggested that coronavirus patients might benefit from a potent steroid called methylprednisolone. But the study’s preliminary nature and its small number of participants limited its impact: At the time, the Eastern Virginia Medical School guidelines, which have helped guide COVID-19 treatment elsewhere, warned that “this topic is controversial” before summarizing the Wuhan findings and suggesting steroids may help.

Now, those findings have received support from the Recovery study, a University of Oxford clinical trial enrolling over 11,500 patients so far at 175 hospitals in the U.K. Recovery is investigating five potential treatments for COVID-19. One arm of the study, with over 2,100 patients, is investigating the steroid dexamethasone. (With hydroxychloroquine eliminated on June 5, the remaining candidates in the study are the anti-HIV combination drug Kaletra, the antibiotic azithromycin, plasma from recovered patients, and an anti-inflammatory called tocilizumab.)

The chief investigators write:

Dexamethasone reduced deaths by one-third in ventilated patients … and by one-fifth in other patients receiving oxygen only. ... There was no benefit among those patients who did not require respiratory support.

Based on these results, 1 death would be prevented by treatment of around 8 ventilated patients or around 25 patients requiring oxygen alone.

This is excellent news, for several reasons. The first is obvious: A drug has now demonstrated clinical benefit for COVID-19 patients in a large, well-run trial. The second reason is less obvious but equally significant: Dexamethasone is cheap, easily manufactured, and generally well tolerated in short courses. It lacks the harsh side effects of hydroxychloroquine. Unlike remdesivir, its supply is so plentiful that it is routinely given to prevent nausea in surgical patients. Nor are pharmaceutical patents an issue—dexamethasone has been in clinical use for about 60 years, so generic manufacturers worldwide can produce it.

Every answer in research raises more questions. Steroids are not a single drug but an entire class of them (dexamethasone belongs to the group called glucocorticoids, distinct from anabolic steroids, the drugs weightlifters occasionally abuse to bulk up). Which steroid is best? How much should patients receive, and how often? Should other drugs accompany it, to enhance its effect or to mitigate side effects? How will diabetics, who are prone to severe COVID-19 but whose blood sugar often rises significantly with steroid therapy, fare?

Another logical question is how we should respond, in terms of treatments and preventive efforts. This one is simpler: Outside of the hospital, little needs to change, because dexamethasone does not prevent coronavirus infection. Nor does the drug help minor COVID-19 cases, since it appears to work by tapping the brakes on the “cytokine storm” of an overactive immune system response to the virus. Because of this, patients only benefit from it once their condition is serious enough that they’re in the hospital, receiving oxygen or on a ventilator. (Patients in the Recovery trial showed no benefit from dexamethasone until that point.)

The recent study retractions in The Lancet and The New England Journal of Medicine have hurt public trust in medical research, especially in an environment where statements for or against a given drug often reflect political leanings. A cheap, effective, and uncontroversial drug that truly helps COVID-19 patients is the medical research world’s first step toward regaining its own health.