A drug named dexamethasone is the talk of the hour given recent claims that it can cut mortality in patients with severe forms of Covid-19 by a third. The claims originated in a press release issued by scientists involved with the RECOVERY (short for ‘Randomised Evaluation of Covid-19 Therapy‘) trial, from the University of Oxford. They have said that the trial data suggests that dexamethasone cuts the risk of death by one-third in patients with ventilator support and by one-fifth in patients requiring oxygen support.
This said, it’s important to note that their announcement was preliminary in nature: the study’s underlying data isn’t available yet for independent verification.
Dexamethasone is not a novel drug. It is an often-used steroid with powerful anti-inflammatory properties. Dexamethasone falls under a broader class of drugs called corticosteroids, which in turn has two sub-classes: glucocorticoids and mineralocorticoids. Glucocorticoids have anti-inflammatory activity. Mineralocorticoids regulate electrolyte and water balance in the body.
Dexamethasone is a glucocorticoid drug and its action is generic. It is administered for various conditions, including arthritis, immune system disorders and allergic reactions of the skin, eyes and ears.
In Covid-19 patients, dexamethasone serves to dampen the body’s immune response when it becomes too aggressive to control by other means.
An inflammation refers to the body’s immune response to an invading pathogen, and an infection refers to the pathogen’s effects and the inflammation together. As such, an inflammatory reaction is vital for the body to clear a pathogen, thus eliminating the infection.But in many terminally ill Covid-19 patients, the body mounts an unrestrained inflammatory response: it rapidly produces proteins called cytokines to fight the infection, but the cytokines also attack and damage the body’s own cells and tissues.
Eventually, fluid accumulates in the lungs’ air sacs and the patient struggles to breathe. This condition is called acute respiratory distress syndrome (ARDS), and is often fatal.
To understand how dexamethasone works, it’s important to understand how an uncontrolled inflammation plays out. Every inflammation begins with a cascade of biochemical reactions. First, the phospholipid membranes of cells secrete arachidonic acid with the help of an enzyme called phospholipase A2. Arachidonic acid is converted to several inflammatory mediators, including cytokines, prostaglandins and leukotrienes, thanks to the enzyme called cyclooxygenase. These mediators then prompt the body’s cells and blood vessels to fight the infection.
Nearly all cells in the body express receptors for dexamethasone. And when dexamethasone binds with these receptors, it forms a complex – a bigger molecule – inhibits the enzyme phospholipase A2 and blocks the synthesis of the inflammatory mediators. While antiviral drugs like remdesivir attempt to keep the novel coronavirus from replicating inside cells, dexamethasone simply counteracts the body’s heightened inflammatory response.
In Covid-19 patients, such a pronounced inflammatory response occurs only in the terminal stages of the infection. This could explain why dexamethasone was found to be efficacious in patients who are critically ill and depend on ventilator support.
Currently, dexamethasone is very cheap: a strip of 10 tablets costs a princely sum of Rs 3. It’s widely available and hasn’t been patented thus far. If independent verification studies do confirm the RECOVERY trial’s results, the drug’s potential to be a breakthrough will depend on whether the companies and governments involved in the drug’s production and distribution keep the price low, even in the face of rising demand, and ensure sufficient supply.
This said, it’s important to understand that dexamethasone is also an immunosuppressive drug. Studies have found that patients with severe Covid-19 have a low number of cells called T-lymphocytes in their blood. Using dexamethasone could further deplete the T-lymphocyte population and worsen immunosuppression. High doses of dexamethasone can also have side effects like dizziness, irregular heartbeats and increased blood sugar levels.
Finally, it bears repeating that the results based on which the dexamethasone hype has taken root are preliminary. The researchers involved with the trial are yet to publish complete data on the case histories of patients enrolled in the trial. The same preliminary reports also indicate that dexamethasone didn’t have any benefits in patients with milder symptoms, and the trial did not test its efficacy as a prophylactic. So while dexamethasone is the talk of the hour, it also warrants patience – hard though that may be.
(Niranjana Rajalakshmi is a veterinary microbiologist.)