Dexamethasone should be a standard drug in severe COVID-19

By Dr. Liji Thomas, MDAug 3 2020

The current pandemic of COVID-19 is mostly asymptomatic or causes only mild symptoms. However, in a significant minority, it leads to severe or life-threatening disease, often requiring oxygen supplementation or mechanical ventilation in the intensive care unit. In this subset of patients, in the UK, over a quarter died, and if only those patients who need ventilatory assistance are considered, more than 37% die of the condition.

Study: The potential health and economic impact of dexamethasone treatment for patients with COVID-19. Image Credit: David Benito

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Many scientists have explored the use of new as well as already approved drugs for this condition, and one of the very few promising leads is dexamethasone. Dexamethasone is a corticosteroid, which has been reported in some earlier studies to reduce mortality in these patients by 18% and 36% in COVID-19 patients who are on oxygen and ventilators, respectively. A new research paper published on the preprint server medRxiv* in July 2020 reports the findings of dexamethasone use in such patients.

The researchers from the University of Oxford advise dexamethasone should promptly be adopted as a standard treatment for patients with respiratory distress. This treatment, if given in accordance with the current guidance on patient eligibility for oxygen therapy, even where access to oxygen is limited, could save hundreds of thousands of lives in the coming six months of the pandemic,” especially if mobility restrictions and other non-pharmaceutical interventions become impossible to sustain.

Assessing Deaths in Next Six Months

The study uses infection fatality rates (IFR) as a measure of the transmissibility and lethality of the virus. IFR is a crucial metric in finding the relationship between the number of infections and deaths, which is required to predict the number of deaths during the next wave under various conditions.

Many papers have described antibody studies from May onwards, in an attempt to find the exposed proportion of the world population. Investigators estimate that about 7% of people in the UK have been exposed to the infection, and about 40,000 deaths have occurred. The current study estimates that about 6,700 fewer deaths would have occurred with the use of dexamethasone if about 60% of the patients were on oxygen and about 17% on ventilatory support.

The researchers also point out that a reasonably accurate IFR can be used to predict the transmission changes over the next six months and the deaths correlating with such pandemic dynamics, ignoring potential changes in future non-pharmacological interventions. They used the age-stratified population of a country, along with estimates for the IFR and hospitalization rates in various age groups, to find the expected number of admissions and deaths over the next six months from the projected number of infections.

Effect of Dexamethasone on Mortality

After defining their criteria for COVID-19 diagnosis, in mainly clinical terms, and assuming similar hospitalization and age-dependent case fatality rates in the UK as in France, they developed an algorithm that can simply take the number of infections and spit out the number of expected hospitalized cases for each age group. This will then help to estimate the expected mortality if patients are given and not given dexamethasone, and the difference in lives lost. The conclusion is that 12,000 deaths are likely to be saved over the next six months if all the patients received dexamethasone as required.

However, while this kind of access to the drug is possible in the UK, it may not be the case in low- and middle-income countries (LMICs), and these countries may not have resources sufficient to ensure an adequate supply of oxygen or ventilators either. Lacking such intensive medical support, it may be challenging to identify the full effect of dexamethasone globally.

To evaluate, the researchers applied simulations to predict the outcome if all patients were to get dexamethasone once they satisfied the conditions for oxygen prescription, under two conditions: one, they received oxygen; second, they failed to.

Simulations Showing Differential Mortality

They made two different assumptions to generate these simulations: one was that dexamethasone would affect patients who required respiratory support and got it in the same way as patients who needed but failed to get such support. The rationale was the anti-inflammatory action of dexamethasone, which might slow the progression of severe COVID-19 to respiratory failure. The second was that dexamethasone would be effective only if respiratory support was provided. In these two simulated situations, the number of lives saved in potential was 650,000 and 390,000, respectively.

Implications

The advantages of dexamethasone include its affordability, long history of use, and good safety record. Its economic aspects were studied in the UK, in the current research, and include a saving of £8,200 and £760 per life saved and life-year saved, respectively, which makes it a cost-effective treatment option.

The researchers consider that a second wave is inevitable as restrictions on movement wane globally. They sum up: dexamethasone is ideally placed as a candidate standard therapeutic option for COVID-19 patients with respiratory distress, which could significantly reduce the future mortality burden of this disease cost-effectively. The adoption of a dexamethasone treatment protocol for patients requiring respiratory support could potentially lead to a significant number of lives saved over the course of the next six months of the pandemic.”

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources