This will surely not be the last time Doc Gumshoe turns his attention to the pandemic that is now imposing misery on many parts of the world. I need to acknowledge that when what was then generally called the Wuhan virus first came to my attention, I expressed the view that, despite the dire warnings that several infectious disease scientists had stated, it would not become a pandemic. I’m thankful that I was somewhat tentative in expressing that view, but at that point I thought it would be no worse than SARS or MERS, which were also caused by related corona viruses.
But that was back in January. At that point there were only a handful of confirmed cases in the US, and no deaths. I don’t need to remind you of the current case and fatality counts here in the US. But projections for other parts of the globe are staggering. For example, the Institute for Health Metrics and Evaluation (IHME) at the University of Washington is forecasting that about 440,000 people will die from COVID 19 in Latin American and Caribbean nations by October 1st. IHME bases the projection on a careful examination of each nation’s current data about COVID deaths and infections. There is certainly reason to question the accuracy of the figure, based on errors in previous IHME projections. For example, on May 1st, IHME projected that the fatality rate in the US would reach 72,500 by August 1st. However, by July 1, the US fatality rate from COVID 19 had already reached 128,574. At this point in time, the CDC predicts that there will be between 140,000 and 160,000 COVID 19 deaths by July 25th. So if the CDC is right, IHME’s projection is about 100% too low. What does that say about COVID 19 projections overall? Could the deaths in Latin America reach 800,000 or more by October 1st?
I cite those projections/predictions to show just how unpredictable, and how genuinely dire, the course of this pandemic is turning out to be. However, not all the news is bad, and here are a few encouraging items:
Dexamethasone improves survival in COVID patients with the most severe disease
This is based on a trial in the UK dubbed RECOVERY, which has not yet been published, or peer-reviewed. The trial randomly assigned hospitalized patients with COVID 19 to one of several open-label treatments with existing drugs, including not only dexamethasone, but also tocilizumab (Actemra), plasma from convalescent COVID patients, azithromycin, and ritonavir/lopinavir (Kaletra). The hydroxychloroquine arm was stopped on June 5 when it became clear that it conferred no benefit.
Patients receiving dexamethasone were the first to benefit from improved survival compared with those patients receiving usual treatment. In the trial, 2,104 patients received 6 mg of dexamethasone via intravenous injection for ten days, compared to 4,321 patients receiving usual treatment.
Benefit from dexamethasone treatment was seen only in patients receiving a form of respiratory support. In patients who were on mechanical ventilation, deaths in the dexamethasone arm were reduced by 35% compared with patients in the usual-care arm. In patients who were receiving supplementary oxygen, the mortality rate was reduced by 20%. In both cases, these results were judged to be highly significant – P = 0.0003 for patients on mechanical ventilation, and P = 0.0021 for those on supplementary oxygen. The investigators concluded that treating 8 ventilated patients or 25 requiring supplemental oxygen would prevent one death.
Recruitment for this arm of the trial was stopped early because the investigators concluded that they had sufficient evidence of the benefit of dexamethasone treatment. The chief investigator in the trial, Peter Horby, MD/PhD of the University of Oxford stated, “The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become the standard of care in these patients.” In other words, there would be no further justification in assigning patients to a “usual-care arm” which did not include dexamethasone.
As to why dexamethasone does not confer any benefit to patients before they have reached the stage where they require some form of supplementary oxygen, the explanation put forward by researchers is that, indeed, the COVID disease has three fairly distinct phases. The figure below characterizes the three phases and provides some tentative information as to what the appropriate treatment options might be for each phase.