With the US buying up the world’s stock of Remdesivir, will dexamethasone emerge as the wonder cure to save lives amidst this pandemic?
Researchers have made an exciting discovery in the race to find effective therapies against COVID-19. Dexamethasone, a cheap and widely prescribed steroid, has emerged triumphant in the RECOVERY trial conducted at the University of Oxford. Although the study is yet to be peer-reviewed, the £5 drug has been regarded by many as a therapy with massive potential to help a large number of patients battling the virus. Others worry that the temptation to over-prescribe dexamethasone at this early stage of understanding could have dire consequences.
What is dexamethasone, and why do some scientists and clinicians have doubts about its usage?
So far, dexamethasone is the only drug which has demonstrated a potential to improve survival in patients.
Simply put, dexamethasone is a steroid commonly used to reduce inflammation in a variety of pro-inflammatory conditions, including rheumatoid arthritis. Researchers wanted to evaluate its potential to relieve the lung inflammation associated with COVID-19, in hopes to reduce progression to respiratory failure and death.
The UK RECOVERY trial successfully demonstrated that dexamethasone cut deaths by one-third in mechanically ventilated COVID-19 patients, and by one-fifth in COVID-19 patients on supplemental oxygen. So far, dexamethasone is the only drug which has demonstrated a potential to improve survival in patients. Remdesivir has garnered attention worldwide for speeding up recovery, but it has not yet been shown to enhance survival rates. Moreover, unlike Remdesivir which has essentially been hoarded by the US, dexamethasone is readily available in every country.
To understand how dexamethasone might work, it is important to know how SARS-CoV-2 – the virus responsible for COVID-19 – causes illness. Many of the COVID-19 deaths in patients who are on ventilators are not a consequence of the viral infection itself; rather, a hyperactive immune response may be to blame.
The immune system reverses its role from friend to foe
SARS-CoV-2 dominates the early phase of the disease. Here, symptoms are typically milder and the immune system is crucial in eliminating the virus by eliciting a full blown antiviral response. An inability to clear the virus at this stage can cause the immune system to go into overdrive. Small but potent molecules called cytokines increase in the blood as the disease progresses into the late phase. Cytokines signal to parts of the immune system and coordinate a powerful immune response. Most patients on ventilators have elevated levels of IL-6, a cytokine that acts on inflammatory mediators including macrophages, and this over-active recruitment of immune molecules is dangerous. The immune system reverses its role from friend to foe as the macrophages start to damage the lungs.
Anti-IL-6 drugs such as tocilizumab have shown remarkable efficacy in dampening IL-6 and associated detrimental inflammatory responses. While a more targeted therapy like this might be useful, the drug isn’t very accessible, especially on a global scale.
Dexamethasone is a more desirable drug given its low cost and high availability – especially in developing countries. But dexamethasone does not specifically dampen IL-6; it broadly suppresses the immune system as a whole. This includes suppression of the CD4 T-cells, which collectively mediate immune responses, and the CD8 T-cells, which directly destroy cells infected with SARS-CoV-2. The usage of dexamethasone thus seems counter-intuitive as the natural immune system is currently the only way to eliminate the virus in patients.
As the death toll rises in this pandemic, it is increasingly tempting to consider this steroid the best form of treatment for any COVID-19 patient. But the drug might be risky for the majority of patients with milder disease, who could well fight the virus off with their own immune system. In those cases, dexamethasone could restrict this natural recovery.
At the moment, the general consensus is that the benefits of a low-dose of dexamethasone might outweigh the risks. Given the potential of this therapeutic intervention, officials agree that it seems wise to carry on with rigorous trials of dexamethasone to elucidate the ideal patient population and treatment regimen. This appears to be a step in the right direction towards finding a better treatment for COVID-19.
In the long run, researchers believe that success is likely to be achieved by combination therapy using a two-pronged approach – an antiviral drug to eliminate the virus, and a targeted anti-inflammatory drug to specifically dampen harmful immune responses and prevent collateral lung damage. But this could take time, money and a lot of manufacturing and logistics work to succeed at a global scale. At least for now, it appears that dexamethasone could serve as the leading candidate to help alleviate mortalities in this current crisis.
Written by Simran Kapoor and edited by Ailie McWhinnie.
Simran’s thoughts… COVID-19 has infected the population indiscriminately, but the same can’t be said for how infected patients are treated. The purpose of an anti-COVID-19 treatment is to save lives; all lives. It seems increasingly important to strike a balance between drug cost and efficacy during this crisis. While some drugs may be more effective, are they really the “best” anti-viral drug in this situation if everyone can’t have access to them? Will drugs like dexamethasone be the wonder cure in this case, simply because they are cheap?
